First Year Of Follow-up Research Articles

Prognostic relevance of baseline right ventricular echocardiographic evaluation in patients undergoing valvular surgery with tricuspid intervention

Abstract Background Tricuspid valve (TV) intervention is frequently performed both as part of multivalvular surgery and as an isolated procedure. Tricuspid regurgitation (TR) significantly worsen right ventricular (RV) function, which is a prognostic determinant in many clinical scenarios. Purpose Our aim was to evaluate the relevance of baseline right ventricular (RV) baseline echocardiographic in the prognosis after tricuspid valve surgery (TVS). Methods Retrospective observational study of patients undergoing TVS between 2009 and 2022 in our tertiary centre. Baseline right chambers echocardiographic parameters were evaluated: RV diameters (basal, mid and longitudinal), TAPSE, fractional area change (FAC), Doppler tissue velocity of the tricuspid annulus (RVS´) and free wall- (FW-) and 4 chambers- (4C-) global longitudinal strain (GLS). Likewise, systolic pulmonary artery pressure (sPAP) and left ventricular ejection fraction (LVEF) were collected among other variables. Association of echocardiographic parameters with major clinical events at year was explored. Results Finally 273 consecutive patients (71 ± 10.5 years old, 66.7% female) that underwent valvular surgery with tricuspid intervention were included. Multivalvular procedure was performed in 81.3% (50.6% mitral and tricuspid, 25.6% mitral, aortic and tricuspid and 5.1% aortic and tricuspid) and EuroScore was 5 [3-9]. The most common TV lesion was TR (97.8%), functional in 84.2%. The main surgical technique was tricuspid annuloplasty with prosthetic ring (57.9%). Preoperative echocardiographic parameters are presented in Table. Baseline LVEF was 59 [53-65]%. The most frequent postoperative complication was low output (23.4%) and there was an overall mortality rate of 8.3% during the first year of follow-up. Postsurgical low output state was associated with vena contracta TR (0,78 vs 0,66 cm; p <0.001) and 4C-GLS ((-15.7 vs -17.3%; p= 0.03). None of the baseline echocardiographic variables was associated with early mortality. Conclusions Baseline RV echocardiographic parameters were associated with postoperative low output but not mortality. The relatively preserved RV dimensions and function in our series may explain these findings. Table. Baseline RV echocardiographic variablesTable

Utility of telephone text messages in secondary prevention after acute coronary syndrome

Abstract Introduction The recurrence of events in patients after an acute coronary syndrome (ACS) represents a great challenge for the health systems due to its high prevalence, morbidity and mortality, and cost. For this reason, secondary prevention measures with low cost and easy to implement are necessary. The objective is to evaluate the usefulness of telephone text messages (TTM) in the control of risk factors and reduction of events in the first year after an ACS. Methods Single-blind 1:1 randomized clinical trial in consecutive patients discharged with ACS between May 2019 and October 2021 in our center. The intervention group received a monthly TTM for 12 months with the recommendations of the Spanish Society of Cardiology regarding secondary prevention measures. Both groups followed the usual review protocol of our center in a specific ischemic heart disease consultation at 3 and 12 months after discharge. The center lacks cardiac rehabilitation. The objectives of the study at 12 months were: total and cardiovascular death, myocardial infarction, stroke, weight, blood pressure, LDL, HDL, triglycerides, glycosylated hemoglobin, smoking habit, and hours of exercise per week. The evaluator in charge of collecting data after the end of the year was unaware of the assignment group. Results N= 370. The patient profile was the usual one for ACS, with a mean age of around 65 years and 25% diabetic, with no differences in any of the baseline characteristics between both groups. An invasive approach was performed in almost all of the subjects, with percutaneous intervention in three-quarters of the cases and also without significant differences in the type of treatment, percentage of multivessel disease, and left main disease between both groups. Only a lower number of stents per patient was recorded in the control group. There were also no differences in medical treatment between both groups. The results are shown in the table. Conclusions In our study, monthly TTM had no influence on the control of risk factors or clinical events during the first year of follow-up after an ACS, and therefore it is not cost-effective to allocate resources for this purpose.

A higher adherence to perindopril-based anti-hypertensive therapy is associated with a reduced risk of cardiovascular outcomes and all-cause mortality in real clinical practice in Italy

Abstract Background Therapeutic management of hypertension is a landmark of cardiovascular (CV) risk prevention. Combined therapies with at least 2 anti-hypertensive agents are required in many patients in whom monotherapy and lifestyle interventions failed in blood pressure control. It is well-known that poor medication adherence remains a major barrier to achieving the therapeutic targets for all CV drugs, including anti-hypertensives. Purpose We evaluated the relationship between adherence to perindopril (PER)-based therapeutic regimen prescribed as single-pill combination (SPC) or free-pill and CV outcomes and all-cause mortality in a large Italian population. Methods A retrospective analysis was performed using administrative databases corresponding to around 6.7 million health-assisted residents. Hypertensive adults were first identified through hospitalization discharge diagnosis or exemption codes for hypertension between 2010 and 2021. Patients prescribed PER-based therapies were screened for all combinations of PER with amlodipine (AML) and/or indapamide (IND) (all formulations, single-pill or free-pill). Time of the first prescription of a PER-based regimen during the inclusion period was considered the index-date. The analysis included all hypertensive subjects prescribed a PER-based therapy, having available data at least 12 months before and 24 months after the index-date, respectively. Since the analysis was focused on the possible associations between adherence level and CV outcomes and all-cause mortality, adherence was assessed during the first year of follow-up on alive patients and outcomes were assessed during the second year. Adherence was assessed using the proportion of days covered (PDC) approach on 1-year follow-up, and considering a PDC<80% as poor-to-moderate adherence, and PDC ≥80% as good adherence. The Cox’s proportional hazard model was applied to estimate Hazard Ratio (HR) adjusting for baseline covariates, including comorbidity profile and pill burden. Results The included cohort (N=24,476) was divided into sub-groups according to adherence in poor-to-moderate (N=6,781) and good adherent patients (N=17,695) with a mean age of 64.8±13.3 and 64.6±11.9 years old, respectively. The Cox’s proportional hazard model showed that good adherence was associated with a relative risk reduction of 23% in all-cause mortality (Table 1A), 21% in all CV events (Table 1B), 17% in ischemic heart disease (Table 1C), 33% in cerebrovascular events (Table 1E), and 22% in the composite outcome of CV events/all-cause mortality (Table 1G). Conclusions The present analysis provided evidence from the Italian real clinical practice that good adherence to PER-based anti-hypertensive therapy results in significantly lower cardiovascular risk and all-cause mortality. These data further emphasize the importance of promoting cost-effective measures to increase medication adherence in patients on anti-hypertensive treatment.

Trajectories in smoking habits and outcomes in patients with stable coronary artery disease

Abstract Background Smoking is a well-identified risk factor for recurrent cardiovascular (CV) events in patients with stable coronary artery disease (CAD). However, smoking status is not binary, and there is a wide diversity of smoking habits trajectories within this population, with different consequences on residual CV risk. Purpose To better understand how smoking status evolves in patients with CAD, and how it is associated with subsequent CV events. Methods We analysed the CLARIFY registry, which included 32,378 patients with CAD. We defined groups according to smoking status at inclusion in the registry: never, former and active smokers. For former smokers, we assessed the timing of definitive smoking discontinuation and its relationship with subsequent CV events. For active smokers, we investigated the association between smoking reduction or discontinuation in active smokers with outcomes. Our primary endpoint was the occurrence of MACE defined by CV death or myocardial infarction (MI) during the 5-year follow-up period adjusted on known predictors for MACE in CAD patients. Results At inclusion, 13,366 (41.3%) patients had never smoked, 14,973 (46.2%) were former smokers, and 4,039 (12.5%) were current smokers, after an average of 6.5 (±6.3) years following CAD diagnosis. In former smokers that were smoking at the time of CAD diagnosis, 72.8% definitively discontinued smoking within the first year following diagnosis, while only 27.2% quit in subsequent years. Each additional year of active smoking after CAD diagnosis increased the risk of MACE (adjusted HR [aHR] 1.08, 95% CI 1.04-1.12 per year). However, regardless of the duration of smoking cessation, former smokers did not return to the cardiovascular risk levels observed in individuals who never smoked (figure). In active smokers at inclusion, smoking cessation was associated with improved CV outcomes, irrespective of the timing of cessation during follow-up (aHR 0.56, 95% CI 0.42-0.76, p < 0.001). Among active smokers, 25.7% reduced their quantity smoked within the first year of follow-up without quitting, but this did not significantly reduce the rate of CV death and MI (aHR 0.96, 95% CI 0.74-1.26, p = 0.78) compared to other active smokers. Conclusion In active smokers diagnosed with CAD, the vast majority of definite quitters cease smoking within the first year of CAD diagnosis. Each subsequent year of active smoking adversely affects CV outcomes. Smoking cessation at any time significantly reduces the risk of CV death or recurrent MI compared to persistent active smokers, although CV risk of former smokers does not decrease to the levels observed in never-smokers. Finally, smoking quantity reduction is not enough to reduce CV risk in this population. These findings underscore the critical importance of timely interventions for smokers diagnosed with CAD, and emphasize that when it comes to smoking cessation, sooner is better, but it is never too late.

Sleep Irregularity and the Incidence of Type 2 Diabetes: A Device-Based Prospective Study in Adults.

To prospectively examine the association between device-measured sleep regularity and incidence of type 2 diabetes (T2D) in a population-based sample of adults. We also examined if meeting sleep duration recommendations attenuated or eliminated the effects of irregular sleep on T2D. We conducted a prospective cohort study of adults aged 40-79 years participating in the UK Biobank accelerometer substudy. Participants wore wrist-attached accelerometers for a duration of 7 days, which was used to compute the Sleep Regularity Index (SRI). Participants were categorized as irregular (SRI <71.6), moderately irregular (SRI between 71.6 and 87.3), and regular (SRI >87.3) sleepers. T2D diagnosis was obtained through self-reports and health records. We analyzed data from 73,630 individuals observed for 8 years, without a history of T2D and without an event in the first year of follow-up. Compared with regular sleepers, irregular (hazard ratio [HR] 1.38; 95% CI 1.20-1.59) and moderately irregular sleepers (HR 1.35; 95% CI 1.19-1.53) were at higher risk of T2D incidence. Dose-response analyses treating SRI as a continuous measure showed higher T2D incidence with SRI scores <80. Meeting current sleep duration recommendations did not counteract the adverse effects of irregular (HR 1.35; 95% CI 1.09-1.66) or moderately irregular (HR 1.29; 95% CI 1.08-1.54) sleep on T2D incidence. Moderate and high sleep irregularity were deleteriously associated with T2D risk, even in participants who slept ≥7 h per night. Future sleep interventions will need to pay more attention to consistency in bedtimes and wake-up times, in addition to sleep duration and quality.

Prodromal Alzheimer's Disease: Global Cognition, Cue Efficiency, and Cerebrospinal Fluid Neurofilament Light Values Predict Short-Term Conversion to Dementia.

Predicting which patients with prodromal AD (pAD) will imminently convert to dementia may be paramount in a memory clinical setting, especially with potential disease-modifying therapies on the horizon. To explore a practical tool for this prediction, combining cognitive tests and cerebrospinal fluid (CSF) biomarkers. We designed a longitudinal prospective, observational, and multicenter study, enrolling patients with pAD. Inclusion criteria comprised memory complaints, Mini-Mental State Examination (MMSE) score of≥22, memory impairment as indicated by the Free and Cued Selective Reminding Test with Immediate Recall (FCSRT + IR) and/or TMA-93, Clinical Dementia Rating-Global Score (CDR-GS) of 0.5, and positive CSF Aβ42/Aβ40 ratio (<0.095, Euroimmun). The primary outcome was the conversion to dementia (CDR-GS≥1) within the first year of follow-up, referred to as "short-term conversion". A multiple regression logistic model was adopted to design the "Predict Short-Term Conversion" (PSTC) score. Between 2020 and 2022, 83 patients were recruited. The median age was 74, with 49.4% being women. Twenty-five (30.1%) patients were classified as short-term converters. The PSTC score incorporated baseline scores on MMSE ( ≤24 = 3, >24 = 0) and FCSRT + IR Total Recall ( ≤14 = 4, >14 = 0), and CSF neurofilament light chains (NfLs) concentrations (β=0.001299). The PSTC score demonstrated an area under the curve of 0.78 (95% CI: 0.67-0.90, p < 0.001), with a cutoff value of 5.14 presenting 76% sensitivity and 80% specificity. The PSTC score, comprising two relatively brief cognitive test scores and NfLs CSF concentrations, could be useful for predicting short-term converters among patients diagnosed with pAD.

Cancer Risks of Patients with Graves' Disease Who Received Antithyroid Drugs as Initial Treatment: A Nationwide Population-Based Analysis.

Background: Population-based studies that examine the associations between hyperthyroidism and cancer risk have yielded inconsistent results. It remains unclear whether the risks of different cancers increase in patients with Graves' disease (GD) who received antithyroid drugs (ATDs) as initial treatment. We aimed to determine whether cancer risk increases in patients with GD, compared with controls. Methods: This nationwide retrospective cohort study utilized data from the National Health Information Database of South Korea. We included 29,502 patients aged >20 years with GD, who received ATDs as initial treatment, and 57,173 age- and sex-matched controls. The primary outcome was the incidence of various types of cancers. Hazard ratios (HRs) with confidence intervals (CIs) for cancer risk were estimated using Cox proportional hazards models. We also analyzed HR by follow-up period since the diagnosis of GD, accounting for surveillance effect. Results: The risk of biliary tract and pancreatic cancers (HR: 1.41, CI: 1.24-1.60), thyroid cancer (HR: 15.51, CI: 12.29-19.57), prostate cancer (HR: 1.48, CI: 1.28-1.71), and ovarian cancer (HR: 1.31, CI: 1.13-1.52) was elevated in the GD group than in the control group even after the first year of follow-up was excluded. The increased risk of these cancers persisted after a follow-up period of more than 5 years. The risk of thyroid cancer in patients with GD was higher during the initial follow-up period (1 to <2 years) (HR: 19.35, CI: 7.66-48.87) compared with that in the follow-up period exceeding 2 years. The cancer risk estimates remained significant after excluding patients with GD who underwent subsequent radioactive iodine therapy. Conclusion: In this large-scale population-based study, GD was associated with increased risks of biliary tract and pancreatic, prostate, ovarian, and thyroid cancers. The increased risk of thyroid cancer, particularly during the initial follow-up period, may be a surveillance effect.

The long-term impact of increased red blood cell distribution width detected during hospitalization for heart failure.

Aim: We determined the long-term role of increased RDW (red blood cell distribution width) detected during cardiac decompensation.Methods: We followed 3697 patients [mean age 71.4years (±SD 10.1), 59.1% males] hospitalized for acute heart failure (HF) and assessed the five-year all-cause mortality risk associated with tertiles of RDW.Results: Patients with RDW in the top tertile showed roughly twofold higher 5-year mortality risk than those in the bottom tertile. The association remained significant not only after adjustments for potential covariates but even if we excluded patients who deceased during the first year of follow-up [HRR 1.76 (95% CIs:1.42-2.18), p<0.0001].Conclusion: The high degree of anisocytosis represents an independent predictor of poor prognosis in HF patients, even long-term after an acute manifestation.

The role of FEV1/FVC in the prediction of acute exacerbation of COPD

BackgroundWhether the ratio of forced expiratory volume in 1 s to forced vital capacity (FEV1/FVC) can be used as a biomarker to predict the risk of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is unclear. MethodsTo investigate the predictive role of FEV1/FVC for AECOPD, we analyzed data from an observational and multicenter cohort study of 2043 patients with COPD in KOREA. Exposures were post-bronchodilator FEV1/FVC and/or percentage predicted FEV1 (FEV1%pred). The outcome was the development of AECOPD during the first year of follow-up. ResultsDuring the first year of follow-up, the proportion of patients who developed AECOPD increased as FEV1/FVC decreased (P < 0.01). FEV1/FVC and FEV1%pred had similar predictive power for AECOPD, with optimal predictive cut-offs of approximately 0.5 for FEV1/FVC and 50 % for FEV1%pred. When the participants were classified into groups based on these cut-offs, compared with a high both-lung function group (FEV1/FVC≥0.5 and FEV1%pred≥50 %), the low-FEV1 group (FEV1/FVC≥0.5 and FEV1%pred<50) had a modestly increased risk of severe AECOPD (adjusted odds ratio[aOR] = 3.12; 95 % confidence interval[CI] = 1.59–6.16), while the risk of severe AECOPD was the highest in the low both-lung function group (FEV1%pred<50 % and FEV1/FVC<0.5) (aOR = 5.16; 95 % CI = 3.34–7.97). ConclusionsFEV1/FVC is a spirometric biomarker predictive of AECOPD. In countries where FEV1%pred is not available for their population, FEV1/FVC could be used as a biomarker for assessing the risk of AECOPD. In countries where accurate FEV1%pred is available, both FEV1%pred and FEV1/FVC could be used to provide additional information to assess the risk of AECOPD. Key messageThis study showed that FEV1/FVC had similar predictive power for AECOPD compared with percentage predicted FEV1. Furthermore, the use of both FEV1 and FEV1/FVC provides additional information for the risk assessment of AECOPD.

Supporting follow-up care in colorectal cancer patients: first experiences with the Assessment of Burden of ColoRectal Cancer (ABCRC)-tool.

The Assessment of Burden of ColoRectal Cancer (ABCRC)-tool is a unique tool that includes a PROM focused on health-related quality of life (HRQoL), functional outcomes and lifestyle assessment. Furthermore, it provides visualization of results and treatment advice. The tool aims to support follow-up consultations of colorectal cancer (CRC) patients. The purpose of this study was to evaluate the first experiences of patients and healthcare professionals (HCPs) with the ABCRC-tool. The ABCRC-tool was implemented in two Dutch hospitals and used by 25 patients and 5 HCPs during follow-up care. Consultations were audio-recorded and their content was analyzed independently by two researchers. Semi-structured interviews with patients and HCPs were conducted after the consultation. Interviews focused on the overall experience with the tool, ease of use, interpretation of the PROM and the visualized results and on the added value of the tool. Audio recording revealed that multiple topics, relevant to patients, were discussed during consultations with the ABCRC-tool. Patients and HCPs appreciated the ABCRC-tool as it added structure to the consultation, was helpful in the preparation of consultations and provided useful and convenient treatment options. The tool was easy to use, and the visualization was clear and informative. HCPs suggested that the tool is likely to be most relevant for patients in the first year of follow-up. This study implies that the ABCRC-tool is of added value for patients and their HCPs. Future research should focus on the evaluation of broad implementation, across a wide range of CRC patients. The ABCRC-tool is a valid tool to support CRC survivors and HCPs to monitor and visualize experienced burden of disease and lifestyle parameters in order to optimize personalized care.

Factors associated with long-term opioid use among patients with axial spondyloarthritis or psoriatic arthritis who initiated opioids.

Up to one in five patients with axial spondyloarthritis (AxSpA) or psoriatic arthritis (PsA) newly initiated on opioids transition to long-term use within the first year. This study aimed to investigate individual factors associated with long-term opioid use among opioid new users with AxSpA/PsA. Adult patients with AxSpA/PsA and without prior cancer who initiated opioids between 2006-2021 were included from Clinical Practice Research Datalink Gold, a national UK primary care database. Long-term opioid use was defined as having ≥3 opioid prescriptions issued within 90 days, or ≥ 90 days of opioid supply, in the first year of follow-up. Individual factors assessed included sociodemographic, lifestyle factors, medication use and comorbidities. A mixed-effects logistic regression model with patient-level random intercept was used to examine the association of individual characteristics with the odds of long-term opioid use. In total 10 300 opioid initiations were identified from 8,212 patients (3037 AxSpA; 5175 PsA). The following factors were associated with long-term opioid use: being a current smoker (OR : 1.62; 95%CI : 1.38,1.90), substance use disorder (OR : 2.34, 95%CI : 1.05,5.21), history of suicide/self-harm (OR : 1.84; 95%CI : 1.13,2.99), co-existing fibromyalgia (OR : 1.62; 95%CI : 1.11,2.37), higher Charlson Comorbidity Index (OR : 3.61; 95%CI : 1.69,7.71 for high scores), high MME/day at initiation (OR : 1.03; 95%CI : 1.02,1.03) and gabapentinoid (OR : 2.35; 95%CI : 1.75,3.16) and antidepressant use (OR : 1.69; 95%CI : 1.45,1.98). In AxSpA/PsA patients requiring pain relief, awareness of lifestyle, sociodemographic and prescribing characteristics associated with higher risk of long-term opioid use can prompt timely interventions such as structured medication reviews and smoking cessation to promote safer prescribing and better patient outcomes.

Clinical Outcomes of Pterygoid and Maxillary Tuberosity Implants: A Systematic Review.

Background: This study aimed to assess the survival of implants placed in the maxillary tuberosity or in the pterygomaxillary region of the maxilla, based on a systematic review of the literature. Methods: An electronic search was undertaken in three databases. The cumulative survival rate (CSR) was calculated. The log-rank (Mantel-Cox) test was used to compare the survival distributions between some groups. Results: Thirty-eight studies were included, reporting 3446 implants (3053 pterygoid, 393 tuberosity) in 2245 patients, followed up for a mean ± SD of 61.0 ± 36.3 months (min-max, 1-144). A total of 208 pterygoid and 12 tuber implants failed, with a clear concentration of failures in the first year of follow-up and a 10-year CSR of 92.5% and 96.9%, respectively. The survival of pterygoid implants was lower than that of implants in the maxillary tuberosity (p = 0.006; log-rank test), and the survival of implants submitted to early/delayed loading was lower than that of immediately loaded implants (p < 0.001; log-rank test). Non-splinted implants presented higher failure rates. Few cases of intra- or postoperative complications were reported. Conclusions: Implants placed in the pterygoid process/maxillary tuberosity present a high 10-year CSR, although with lower survival for pterygoid in comparison to tuber implants. Pterygoid/tuber implants that are splinted with other implants may present higher survival rates than those that are not splinted.

Real-world effectiveness of the CoronaVac vaccine in a retrospective population-based cohort in four Colombian cities (2021-2022)

ObjectivesThe National Vaccination Plan against SARS-CoV-2/COVID-19 was launched by the Ministry of Health and Social Protection on 14 February 2021. The main objective of this study was to evaluate the effectiveness of the CoronaVac in preventing the three clinical outcomes of infection, hospitalisation, or death, in a real-world scenario. DesignThis was a population-based retrospective dynamic cohort study using a multivariate Cox model to calculate hazard ratios to estimate vaccine effectiveness from 17 February 2021 to 30 June 2022. The data were collected from surveillance systems for 12 months for each individual. Four cities were selected on the basis of the reliability of their data bases. ResultsThe rates of CoronaVac effectiveness were 32% (95% confidence interval [CI] 31-33) for preventing infection, 55% (95% CI 54-56) for hospitalisation, and 90% (95% CI 89-90) for death, at the end of follow-up. These findings were more consistent during the first 4 months. Compared with the unvaccinated group, homologous booster doses appeared to increase effectiveness in preventing hospitalisation, whereas heterologous booster doses increased protection for both hospitalisation and death. Booster doses did not improve effectiveness among those already vaccinated with CoronaVac, even when they received heterologous boosters. ConclusionsCoronaVac demonstrated effectiveness in preventing death and hospitalisation during the first year of follow-up, but its effectiveness in preventing infection was lower, decreasing rapidly after the first 4 months of follow-up. The effectiveness was higher among children aged between 3 and 12 years, and among adults aged ≥60 years. Booster doses did not improve effectiveness among those already vaccinated with CoronaVac.

Arrhythmia in patients with systemic sclerosis: incidence, risk factors and impact on mortality in a Swedish register-based study

ObjectivesThe objectives of this study are to study the risk of developing cardiac arrhythmia and its subtypes over time in patients with systemic sclerosis (SSc), to assess potential risk factors...

Higher hepatitis B core-specific T cell response is associated with a lower risk of clinical relapse after discontinuation of oral antiviral treatment

BackgroundHepatitis B virus (HBV)-specific T cell response is a major host immune response to control the virus. However, it is still unclear how it affects long-term outcomes of chronic hepatitis B patients, especially those who stop nucleos(t)ide analogue (NA) therapy. We aimed to explore whether the HBV-specific T cell response at the end of treatment (EOT) was associated with clinical outcomes. MethodsIn a prospective cohort study, 51 HBeAg-negative patients who discontinued NA therapy were enrolled. ResultsIn a mean follow-up of 25.3 months, 25 patients developed clinical relapse. We found that a stronger hepatitis B core (HBc)-specific T cell response at EOT was associated with a lower risk of clinical relapse. Compared to the low-response group, the high-response group had a lower risk of clinical relapse with hazard ratio of 0.21 (95% CI: 0.05–0.88). The high HBc-specific T cell response was associated with reduced surge of HBV DNA and HBcrAg during the first year of follow-up. The T cell response at EOT was comparable between different NA treatments. Notably, the overall HBV-specific T cell response could be partially restored along with clinical relapse; however, such reinvigorated T cell response was not associated with HBsAg seroclearance. ConclusionsA higher HBc-specific T cell response at EOT was associated with lower risk of clinical relapse and reduced surge of HBV DNA and HBcrAg levels off NA therapy.

Comparative Transcriptomic Analyses of Peripheral Blood Mononuclear Cells of COVID-19 Patients without Pneumonia and with Severe Pneumonia in the First Year of Follow-Up.

The multisystemic effects of COVID-19 may continue for a longer time period following the acute phase, depending on the severity of the disease. However, long-term systemic transcriptomic changes associated with COVID-19 disease and the impact of disease severity are not fully understood. We aimed to investigate the impact of COVID-19 and its severity on transcriptomic alterations in peripheral blood mononuclear cells (PBMCs) following 1 year of the disease. PBMCs were isolated from the peripheral blood of healthy control donors who did not have COVID-19 (C; n = 13), from COVID-19 patients without pneumonia (NP; n = 11), and from COVID-19 patients with severe pneumonia (SP; n = 10) after 1-year of follow-up. Following RNA isolation from PBMCs, high-quality RNAs were sequenced after creating a library. Differentially expressed genes (DEGs) and differentially expressed long non-coding RNAs (DElncRNAs) were identified using Benjamini-Hochberg correction and they were analysed for hierarchical clustering and principal component analysis (PCA). Intergroup comparisons (C vs. NP, C vs. SP, and NP vs. SP) of DEGs and DElncRNAs were performed and hub genes were determined. Functional enrichment analyses of DEGs and DElncRNAs were made using Metascape (v3.5.20240101) and the first version of NCPATH. The RNA sequencing analysis revealed 4843 DEGs and 1056 DElncRNAs in "C vs. NP", 1651 DEGs and 577 DElncRNAs in "C vs. SP", and 954 DEGs and 148 DElncRNAs in "NP vs. SP", with 291 DEGs and 70 DElncRNAs shared across all groups, respectively. We identified 14 hub genes from 291 DEGs, with functional enrichment analysis showing upregulated DEGs mainly linked to inflammation and osteoclast differentiation and downregulated DEGs to viral infections and immune responses. The analysis showed that 291 common and 14 hub genes were associated with pneumonia and that these genes could be regulated by the transcription factors JUN and NFκB1 carrying the NFκB binding site. We also revealed unique immune cell signatures across DEG categories indicating that the upregulated DEGs were associated with neutrophils and monocytes, while downregulated DEGs were associated with CD4 memory effector T cells. The comparative transcriptomic analysis of NP and SP groups with 52 gene signatures suggestive of IPF risk showed a lower risk of IPF in the SP group than the NP patients. Our findings suggest that COVID-19 may cause long term pathologies by modulating the expression of various DEGs, DeLncRNAs, and hub genes at the cellular level.

Radiogenomics of Intrahepatic Cholangiocarcinoma: Correlation of Imaging Features With BAP1 and FGFR Molecular Subtypes.

Clinical research has shown unique tumor behavioral characteristics of BRCA-associated protein-1- (BAP1-) and fibroblast growth factor receptor (FGFR)-mutated intrahepatic cholangiocarcinomas (CCAs), with BAP1-mutated tumors demonstrating more aggressive forms of disease and FGFR-altered CCAs showing more indolent behavior. We performed a retrospective case-control study to evaluate for unique imaging features associated with BAP1 and FGFR genomic markers in intrahepatic CCA (iCCA). Multiple imaging features of iCCA at first staging were analyzed by 2 abdominal radiologists blinded to genomic data. Growth and development of metastases at available follow-up imaging were also recorded, as were basic clinical cohort data. Types of iCCA analyzed included those with BAP1, FGFR, or both alterations, as well as cases with low mutational burden or mutations with low clinical impact, which served as a control or "wild-type" group. There were 18 cases in the FGFR group, 10 with BAP1 mutations, and 31 wild types (controls). Cases with BAP1 mutations showed significantly larger growth at first year of follow-up (P = 0.03) and more frequent tumor-associated biliary ductal dilatation (P = 0.04) compared with controls. FGFR-altered cases showed more infiltrative margins compared with controls (P = 0.047) and demonstrated less enhancement between arterial to portal venous phases (P = 0.02). BAP1 and FGFR groups had more cases with stage IV disease at presentation than controls (P = 0.025, P = 0.006). Compared with wild-type iCCAs, FGFR-mutated tumors often demonstrate infiltrative margins, and BAP1 tumors show increased biliary ductal dilatation at presentation. BAP1-mutated cases had significantly larger growth at first-year restaging.

Cabozantinib use in second or subsequent line of treatment in renal cell carcinoma: an analysis of Italian administrative databases.

Cabozantinib use in everyday clinical practice for advanced or metastatic renal cell carcinoma (RCC) is relatively recent, and real-world data on treatment persistence, adherence and sequencing are still limited. We conducted an analysis based on an integrated administrative database, covering around 6.9 million health-assisted Italian individuals, to explore the use of cabozantinib for RCC. Patients with at least one prescription for cabozantinib during 2017-2020 were searched. These were characterized during all available period (i.e. from 2010 onwards) before the index date and were observed after inclusion. A total of 113 patients treated with cabozantinib in second or subsequent line were included, and their demographic, clinical and treatment characteristics were described. About half of these RCC patients were aged >65 years (47.8%). Sixty patients (53.1%) were highly adherent to cabozantinib therapy, and the median cabozantinib treatment duration of use was 8.7 months (95% confidence interval: 5.8-11.1). During the first year of follow-up, the average total cost per patient was €32,508. We described second or subsequent line cabozantinib treatment for RCC in a real-world setting and the economic burden of disease in Italy, taking advantage of large, integrated administrative databases.

Infections in patients with mantle cell lymphoma.

Advancements in treatments have significantly improved the prognosis for mantle cell lymphoma (MCL), and there is a growing population of survivors with an increased susceptibility to infections. We assessed the incidence of infections by clinical characteristics and treatment both before and after MCL diagnosis in Sweden. Patients with a diagnosis of MCL ≥ 18 years between 2007 and 2019 were included, along with up to 10 matched comparators. Infectious disease diagnosis and anti-infective drug dispensation were identified by the National Patient and the Prescribed Drug Registers, respectively. Patients and comparators were followed from the diagnosis/matching date until death, emigration, or June 30, 2020. Overall, 1559 patients and 15,571 comparators were followed for a median duration of 2.9 and 5 years, respectively. The infection rate among patients was twofold higher, RRadj = 2.14 (2.01-2.27), contrasted to the comparator group. There was a notable rise in infection rates already 4 years before MCL diagnosis, which reached a fourfold increase in the first year after diagnosis and persisted significantly increased for an additional 8 years. Among patients, 69% (n = 1080) experienced at least one infection during the first year of follow-up. Influenza, pneumonia, other bacterial infections, urinary tract infections, and acute upper respiratory infections were the most frequent. Notably, MCL remained to be the primary leading cause of death among patients (57%, n = 467/817). Infections as the main cause of death were rare (2.6%, n = 21). Our study highlights the importance of thoroughly assessing infectious morbidity when appraising new treatments. Further investigations are warranted to explore strategies for reducing infectious disease burden.

Patients Journey Before Early Rheumatoid Arthritis Diagnosis Contributes to disease's Activity Level: A Real-Life Study.

The help-seeking process in rheumatoid arthritis (RA) patients is challenging, and its study is limited in Latin America. The study describes the real-life journey before patients' incorporation into an early arthritis clinic (EAC) and its impact on baseline and 1-year cumulative disease activity levels. The patient's journey was assessed through a questionnaire that captured the patient's path from the first disease-related symptom to the initial assessment in the EAC. A disease activity (28 joints evaluated)-erythrocyte sedimentation rate (DAS28-ESR) score >5.1 defined a high-disease activity level. The mean of individual consecutive DAS28-ESR scores summarized cumulative DAS28-ESR. Multiple logistic regression analysis identified factors associated with a DAS28-ESR score >5.1 at the first assessment. Linear regression analysis assessed the impact of general practitioner (GP)-first consultant and time on disease-modifying antirheumatic drugs (DMARDs) on baseline and cumulative DAS28-ESR scores. Through January 2023, the EAC had 241 RA patients, among whom 209 (86.7%) completed the patients' journey questionnaire (PJQ) and 176 (84.2%) at least 1 year of follow-up. A GP was the first consultant in 76.6% of the patients, and only 12.4% were prescribed DMARDs. Patients had additional evaluations with either rheumatologists (38.6%) or other specialists (31.6%), and half of them were initiated DMARDs. GP-first consultant (adjusted odds ratio: 2.314, 95% confidence interval: 1.190-4.500, p = 0.013) and time on DMARDs (adjusted odds ratio: 0.738, 95% confidence interval: 0.585-0.929, p = 0.010) were associated with baseline DAS28-ESR score >5.1. The B coefficient magnitudes for GP-first consultant and time on DMARDs to predict cumulative DAS28 progressively decreased during the first year of follow-up. Patients' journey before recent-onset RA diagnosis predicts first-year disease activity levels.