Treatment-naive Patients Research Articles

Epidemiology of thyroid-stimulating immunoglobulin in recent-onset symptomatic thyroid eye disease.

This study aims to report correlations between thyroid-stimulating immunoglobulin (TSI) and both clinical and radiological parameters in recent-onset symptomatic thyroid eye disease (TED) patients. A prospective cohort study of TED patients managed at the Chinese University of Hong Kong from January 2014 to May 2022. Serum TSI levels were determined with the functional assay. Outcomes included the Clinical Activity Score (CAS), marginal reflex distance1 (MRD1), extraocular muscle motility restriction (EOMy), exophthalmos, and diplopia. The radiological assessment included cross-sectional areas and signal of extraocular muscles on STIR-sequence MRI. A total of 255 (197 female) treatment-naive patients, with an average onset age of 50 ± 14 years (mean ± s.d.), were included. Elevated pre-treatment TSI level was observed in 223 (88%) patients. There was a weak positive correlation between TSI and CAS (r = 0.28, P = 0.000031), MRD1 (r = 0.17, P = 0.0080), and the size of the levator palpebrae superioris/superior rectus complex (r = 0.25, P = 0.018). No significant correlation existed between TSI and STIR signals. The AUC and optimal cut-off value for clinical active TED were 0.67 (95% CI: 0.60-0.75) and 284% (specificity: 50%, sensitivity: 85%). In total, 64 patients received intravenous methylprednisolone (IVMP) during the study interval, and they had a higher baseline TSI level than those who did not have IVMP (P = 0.000044). Serial post-IVMP TSI among the 62 patients showed a significant reduction compared to the baseline level (P < 0.001). Both the baseline and post-IVMP TSI levels, and percentages of TSI changes were comparable between patients who responded and did not respond to the first course of IVMP. TSI can be a serum biomarker for the diagnosis, prognosis, and treatment response of TED. Further validation should be warranted.

Automatic three-dimensional reconstruction of the oesophagus in achalasia patients undergoing POEM: an innovative approach for evaluating treatment outcomes

Background and aimsPeroral endoscopic myotomy (POEM) is a standard treatment option for achalasia patients. Treatment response varies due to factors such as achalasia type, degree of dilatation, pressure and distensibility...

The Prevalence of Depression and Its Potential Link to Liver Fibrosis in Patients Diagnosed With Chronic Hepatitis C Virus Infection Prior to the Initiation of Direct-Acting Antiviral Treatment.

Introduction Chronic hepatitis C virus (HCV) infection is associated with various extrahepatic manifestations, including depression. This study aimed to determine the prevalence of depression in treatment-naive HCV patients and explore its potential association with liver fibrosis severity. Methodology A consecutive cohort of 50 treatment-naive HCV patients without coinfections was enrolled over six months. Depression was assessed using the Hamilton Depression Rating Scale (HAM-D), and the liver fibrosis stage was evaluated using Fibroscan elastography. Results The cohort comprised 62% females (n=31) and 38% males (n=19), with ages ranging from 27 to 76 years. HAM-D scores indicated mild depression in 78% (n=39) and moderate depression in 16% (n=8) of patients. Notably, patients with mild depression displayed varying degrees of liver fibrosis (F0, F1, and F2), while all patients with moderate depression had advanced fibrosis (F3).Based on the multiple regression model, fibrosis was a statistically significant independent predictor with an unstandardized regression coefficient(B) of3.115 (p=0.007). Conclusions Our findings point to a high prevalence of depression in treatment-naive HCV patients. Interestingly, there might be a link between depression severity and the stage of liver fibrosis, with advanced fibrosis potentially associated with more severe depression.

Phase 1b/2 study of combination 177Lu girentuximab plus cabozantinib and nivolumab in treatment naive patients with advanced clear cell RCC.

Phase 1b/2 study of combination ¹⁷⁷Lu girentuximab plus cabozantinib and nivolumab in treatment naive patients with advanced clear cell RCC.

Genetic landscape for majority and minority HIV-1 drug resistance mutations in antiretroviral therapy naive patients in Accra, Ghana

BackgroundThe successful detection of drug-resistance mutations (DRMs) in HIV-1 infected patients has improved the management of HIV infection. Next-generation sequencing (NGS) to detect low-frequency mutations is predicted to be useful for efficiently testing minority drug resistance mutations, which could contribute to virological failure. This study employed Sanger sequencing and NGS to detect and compare minority and majority drug resistance mutations in HIV-1 strains in treatment-naive patients from Ghana. MethodFrom a previous study, 20 antiretroviral therapy (ART)-naive participants were selected for a cross-sectional study. Sanger sequencing and NGS techniques were used to detect the majority and minority HIV drug resistance (HIVDR) mutations, respectively, in the protease (PR) and partial reverse transcriptase (RT) genes. NGS detected mutations at 1 % and 5 % frequencies and Sanger sequencing at ≥20 % frequencies. The sequences obtained from NGS and Sanger sequencing platforms were submitted to the Stanford HIV drug resistance database for subtyping, mutation identification, and interpretations. ResultsSequences from the twenty participants where the CRF02_AG was the predominant strain (16, 80 %) were analyzed. NGS detected 25 mutations in the RT and PR genes, compared to 21 mutations by Sanger sequencing. Minority DRMs were detected at the prevalence of 55.0 % with NGS against 35 % DRMs by Sanger sequencing. One of the patients had eight different HIVDR variants, with two minority variants. These mutations were directed against PI (K20I and D30DN), NNRTI (Y181C, M23LM and V108I) and NRTI (K65R, M184I, and D67N). ConclusionThe study affirms the usefulness of genomic sequencing for drug resistance testing in HIV. It further shows that Sanger sequencing alone may not be adequate to detect mutations and that NGS capacity should be developed and deployed in the Ghanaian clinical settings for patients living with HIV.

Identification of immune biomarkers in treatment-naive patients with metastatic pancreatic cancer treated with the GSK-3 inhibitor elraglusib (9-ING-41) in combination with gemcitabine/nab-paclitaxel in the 1801 phase 2 study.

e16331 Background: Elraglusib (9-ING-41), a potent and selective GSK-3 inhibitor, is a targeted anticancer agent with clinical activity in phase 1 trial and undergoing clinical development for the treatment of metastatic pancreatic ductal adenocarcinoma (mPDAC). Elraglusib (9-ING-41) displayed immune-modulatory activity in preclinical models and modulation of serum cytokine profile in clinical specimens. Here, we investigated the correlation between plasma levels of cytokines/chemokines/soluble cell receptors/growth factors (CCSG) and clinical outcomes of patients with mPDAC treated with elraglusib and gemcitabine/nab-paclitaxel (GnP) in an exploratory study. Methods: CCSGs were evaluated in the pre-dose plasma samples of patients with newly diagnosed mPDAC enrolled in the 1801 phase 2 study (NCT03678883) treated with GnP (n = 13) or elraglusib/GnP (n = 32). Using a Luminex immunoassay, 40 CCSGs were screened as predictive biomarkers of median overall survival (mOS) in the elraglusib/GnP arm using 5-fold cross-validation and maximally selected rank statistic cutpoint determination. A subset of CCSGs (n = 10) was remeasured using an MSD immunoassay with greater sensitivity. Maximally selected rank statistic cutpoint determinations were conducted using MSD results for elraglusib/GnP samples with mOS and median progression free survival (mPFS). P values &lt; 0.05 were considered statistically significant. Results: Luminex screening revealed several CCSGs significantly stratified elraglusib/GnP patients by mOS. IL-6 and IL-8 were identified as top candidates with stable and significant results on cross-validation. Using the MSD assay, both were confirmed to stratify elraglusib/GnP patients by OS and extended to analyze PFS. Low level of IL-8 conferred a better OS prognosis (HR: 0.0919, 95%, CI: 0.0205-0.411, P &lt; 0.001) than low IL-6 (HR: 0.205, 95%, CI: 0.063-0.665, P = 0.005) in the elraglusib/GnP treated patients. Correlations with mPFS were similar in the elraglusib/GnP patients for IL-6 (HR: 0.248, 95% CI: 0.072-0.848, P = 0.02) and IL-8 (HR: 0.297, 95%, CI: 0.111-0.743, P = 0.01). Conclusions: Preliminary results of our exploratory study identified low plasma levels of IL-6 and IL-8 prior to elraglusib/GnP treatment as potential predictive biomarkers associated with improved outcomes in previously untreated patients with mPDAC. The 1801 Part 3 Arm B clinical trial recruitment has been completed. We plan to analyze additional pre-dose plasma samples obtained from approximately 200 patients by April 2024. These will be analyzed using interim OS data available by April 2024 and included in the final presentation. Clinical trial information: NCT03678883 .

A blood-based screening test for colorectal cancer (CRC) using methylation sequencing.

e15089 Background: Diagnosis of CRC is biased towards later stages in India (3.8% Stage I, 16.7% Stage II, 50.7% Stage III, 28.8% Stage IV), and five-year survival at &lt; 40% is one of the lowest in the world. A blood-based non-invasive screening test for CRC using cell-free DNA (cfDNA) methylation sequencing is developed here from the blood of 212 controls and 67 treatment naive CRC patients from 21 sites across India and processed in Strand’s reference lab in Bangalore. Methods: Steps involved cfDNA extraction, NEB Enzymatic Methyl-Seq library preparation, Twist Human Methylome hybridisation capture, 2x150bp sequencing on NovaSeq 6000/X. Methylation + fragmentomic features were calculated for each target region. Samples were split randomly into a leave-in set of 170 controls + 53 cancers (I: 8, II 16, III: 23, IV: 6) and a leave-out set of 42 controls + 14 cancers, (I: 5, II: 4, III: 2, IV: 3) with 20 rounds of 4-fold cross-validation done on the leave-in set (random splits). Feature selection per fold was performed using the KS test without access to ¼ of the leave-in set and to the entire leave-out set. Gradient boosted trees with monotonic constraints reflecting the expected association of the scores with cancer were used to build “explainable” models. Test robustness was assessed using differentially methylated regions (DMRs) from other studies, and by assessing predictability using sample metadata alone. Results: At a 91% specificity level, the ensemble model had a median sensitivity of 62.5% for Stage I (95%CI 38%-86%), 87% for Stage II (95% CI 75%-95%), 87% for Stage III (95% CI 75%-95%) and 83.4% for Stage IV (95% CI 84%-100%) in cross-validation, and 60% for Stage I (95%CI 60%-80%), 100% for Stage II (95% CI 80%-100%), 100% for Stage III (95% CI 100%-100%) and 100% for Stage IV (95% CI 100%-100%) on the leave-out set. At a ~98% specificity level, the model had a median sensitivity of 37.5% for Stage I (95%CI 37%-50%), 69% for Stage II (95% CI 56%-75%), 69% for Stage III (95% CI 60%-84%) and 67% for Stage IV (95% CI 50%-84%) in cross-validation, and 40% for Stage I (95%CI 20%-60%), 75% for Stage II (95% CI 75%-100%), 100% for Stage III (95% CI 100%-100%) and 100% for Stage IV (95% CI 66%-100%) with a slight decrease in specificity to 95.2% on the leave-out set. Using DMRs derived from TCGA data and other publications, yielded a comparable (to our models) cross-validation area under the curve (AUC: 0.93-0.95). Cross-validation performance using only the sample metadata in table 1 and without access to the data was significantly poorer (AUC 0.75-0.81). Conclusions: cfDNA-based methylation profiles are consistent across studies and ethnicities, leading to robust and “explainable” CRC screening predictions. [Table: see text]

Survey of long term survivors of oral cancer: Looking beyond cancer biology.

6087 Background: While surgery is the main stay of treatment for early stage oral cancers, advanced stages require adjuvant treatments in the form of radiotherapy or concurrent radiotherapy. Yet, the effectiveness of these interventions is not solely determined by clinical measures but also by personal factors such as individual motivation, support from loved ones, and financial security. These aspects might explain the survival rate variations among patients who, despite having similar prognostic categories and stages of disease, show differing outcomes. The role of social determinants in influencing patient survival, apart from the acknowledged impact of disease biology, is not well understood. Methods: All treatment-naive oral cavity cancer patients who underwent definitive treatment during 2014 to 2018 at our institute and are alive for more than five years were selected for this study. A custom investigator-administered questionnaire was developed and it had 32 questions under six domains- personal, habit history, financial, social, functional, and emotional. The study was approved by the institutional ethics committee. Of the 1787 potential participants, we found that 219 had expired, only 442 patients agreed to answer the questionnaire, while 45 refused to participate. The rest of the patients were not reachable telephonically. Results: This survey had 442 patients, of which 90% were males, with a mean age of 52.1 years. The most common site of the presentation was buccal mucosa (60%), and 59% presented in the locally advanced stage. Post-operatively, 71% received adjuvant therapy. All patients were motivated to undergo the radical treatments and had their family support. However, post-treatment, about 10% of individuals experienced a change in marital status. Financial constraints did affect 20% of patients during and after treatment, and more than 70% had their out-of-pocket expenditure above 50% of the total cost. While 80% did not have trouble attending social functions, 46% reported trouble eating socially. However, this was more common for patients who received adjuvant treatment (p &lt; 0.001). About 21% reported shoulder dysfunction and body discomfort. However, no statistically significant associations could be drawn for any of the domains of the questionnaire when compared to patients between the early and late stages. Shoulder discomfort was experienced more by patients who were treated for tongue cancer (p-value 0.010). Conclusions: The results of this study shed light on the challenges faced by long-term survivors of oral cancer following radical treatment regimens. More than half of patients reported that out-of-pocket expenses constituted more than half of their total treatment costs. A notable minority of people suffer from shoulder dysfunction, suggesting there is a clear opportunity for advancements in reconstruction and rehabilitation.

Unveiling a novel NKG2A inhibitor based on monoclonal antibody to HLAE-peptide complex.

e14677 Background: HLAE is a non-classical MHC class I molecule complexed with the VMAPRTLFL nonapeptide, derived from the leader sequence of HLAG (HLAEpHLAG). HLAEpHLAG is overexpressed across a wide type of tumors prominently on Multiple Myeloma (MM). HLAEpHLAG complex is the ligand to CD94-NKG2A in the immune system which negatively regulates the activation of natural killer (NK) cells as well as NKG2A positive T cells. Harnessing of the HLAE-NKG2A axis by the cancer cells leads to evasion from the immune system attack resulting in cancer progression. Currently, several Immune Checkpoint Inhibitors (ICIs) target the NKG2A receptor which has a low specificity to cancer and high toxicity to the patient. Engineering a new ICI that targets the HLAEpHLAG complex can potentially yield improved outcomes in cancer therapy. Methods: Using the hybridoma system, a new mouse monoclonal antibody (mAb) called 4D7 that targets the HLAEpHLAG complex was developed. mAb 4D7 affinity was assessed in vitro with recombinant proteins and a panel of cell lines that expressed zero to high levels of HLAE. The functional impacts of the mAb 4D7 was examined in a system where various MM cell lines were separately co-cultured with primary NK (pNK) cells. pNK were isolated from the peripheral blood of 5 healthy donors, and their activity was examined in the presence of mAb 4D7 by CD107a degranulation assay. Also, the functional impacts of the mAb 4D7 on allogenic pNK and MM blast cells, isolated from the bone marrow of 6 MM patients were assessed. Results: mAb 4D7 was determined to be an IgG-kappa isotype showing a high specific binding to recombinant HLAEpHLAG. Cell lines with overexpression of membranal HLAEpHLAG: RPMI8226, U266, 721.221 HLAE, and 721.221 HLAG showed positive staining with the mAb 4D7. While cell lines with low to zero expression of HLA-E like 721.221 WT showed low or negative staining with the mAb 4D7. The degranulation of NKG2A+ pNK subset cells against MM target cells increased in presence of mAb 4D7. However, adding mAb 4D7 to NKG2A -pNK subset cells co-cultured with MM target cells did not affect the pNK activity. Similar results were obtained when the target and effector cells were isolated from the bone marrow of active treatment-naive MM patients. Conclusions: MAb 4D7 demonstrates a remarkably high affinity for binding to the HLAEpHLAG complex, ensuring the safety of its application. The ability of 4D7 mAb to effectively block the HLAEpHLAG complex and counteract the inhibition signal in NK cells. mAb 4D7 is a promising monoclonal antibody with substantial potential to serve as an ICI for clinical use in MM patients.

Efficacy and safety of arterial FOLFOX chemotherapy plus anti-PD-(L)1 immunotherapy as first-line treatment for unresectable intrahepatic cholangiocarcinoma: A propensity score matched analysis.

e16189 Background: This study aimed to evaluate the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) plus anti-programmed death (ligand)-1 [PD-(L)1] immunotherapy compared to systemic chemotherapy (SCT) plus anti-PD-(L)1 immunotherapy as first-line treatment for patients with unresectable intrahepatic cholangiocarcinoma (uICC). Methods: In this retrospective study, unresectable treatment-naive ICC patients who were treated with HAIC plus anti-PD-(L)1 immunotherapy [HAIC+αPD-(L)1] or SCT plus anti-PD-(L)1 immunotherapy [SCT+αPD-(L)1] were included. The clinical characteristics, therapeutic outcomes and adverse events (AEs) of patients between the two groups were compared. The propensity score matching (PSM) was performed to minimize biases between groups. Results: From January 2019 to January 2023, a total of 182 patients were enrolled, including 147 patients in HAIC+αPD-(L)1 group and 35 patients in SCT+αPD-(L)1 group. After PSM, 61 and 26 patients were included in the HAIC+αPD-(L)1 and SCT+αPD-(L)1 groups, respectively. The HAIC+αPD-(L)1 group showed longer median overall survival (OS) and progression free survival (PFS) than the SCT+αPD-(L)1 group (OS: 14.5 vs 10.5 months, P = 0.019; PFS: 6.4 vs 10.1 months, P = 0.020). The disease control rate of HAIC+αPD-(L)1 group were higher than those of SCT+αPD-(L)1 group (91.8% vs 69.2%, P = 0.007). The overall incidence of adverse events (AEs) was comparable between the two groups, but the HAIC+αPD-(L)1 group showed a lower incidence of grade 3~4 AEs related to anemia, weight loss and fatigue. Conclusions: HAIC plus anti-PD-(L)1 immunotherapy had acceptable toxic effects and might improve outcomes compared to SCT plus anti-PD-(L)1 immunotherapy as first-line treatment for patients with uICC.

Fibrosis-4 index stratifies risks of hepatocellular carcinoma in patients with chronic hepatitis C

Background and aimsRisk stratification for patients with a higher risk of hepatocellular carcinoma (HCC) is crucial. We aimed to investigate the role of the Fibrosis-4 (FIB-4) index in predicting chronic hepatitis C (CHC)-related HCC. MethodsA retrospective cohort study consecutively included treatment-naive CHC patients receiving longitudinal follow-up at the National Taiwan University Hospital from 1986 to 2014. The clinical data were collected and traced for HCC development. Multivariable Cox proportional hazard regression analysis was used to investigate the predictors for HCC. ResultsA total of 1285 patients in the ERADICATE-C cohort were included. The median age was 54, 56% were females, and 933 had HCV viremia. There were 33%, 38%, and 29% of patients having FIB-4 index <1.45, 1.45–3.25, and ≥3.25, respectively. After a median of 9-year follow-up, 186 patients developed HCC. Multivariable analysis revealed that older age, AFP≥20 ng/mL, cirrhosis, and a higher FIB-4 index were independent predictors for HCC. Compared with patients with FIB-4 index <1.45, those with FIB-4 1.45–3.25 had a 5.51-fold risk (95% confidence interval [CI]: 2.65–11.46), and those with FIB-4 ≥ 3.25 had 7.45-fold risk (95% CI: 3.46–16.05) of HCC. In CHC patients without viremia, FIB-4 index 1.45–3.25 and FIB-4 ≥ 3.25 increased 6.78-fold and 16.77-fold risk of HCC, respectively, compared with those with FIB-4 < 1.45. ConclusionThe baseline FIB-4 index can stratify the risks of HCC in untreated CHC patients, even those without viremia. The FIB-4 index should thus be included in the management of CHC.

Inpatient outcomes of patients with new solid tumors admitted to a comprehensive cancer center.

e23056 Background: Hospitalized cancer patients demonstrate multiple challenges including management of acute illnesses, establishment of the cancer diagnosis, creation of a goal concordant care plan, and post-hospital disposition. Yet, there has been limited research regarding characteristics and outcomes of new to hospital oncology patients. Methods: We performed a retrospective chart review of patients with suspicion or confirmed solid tumor cancer diagnosis who were admitted without an established MD Anderson Cancer Center oncologist. We assessed length of stay, ICU utilization, 30-day readmission rate, inpatient mortality, and discharge disposition. We compared the results to our group’s established oncology patients. Statistical analysis was performed using Chi-squared testing. Results: Between November 2022 and January 2023, 201 unique new patients were reviewed out of 1635 admissions. Of those 103 (51.2%) were males, median age of 60 (range: 22-79), White including Hispanics 118 (59%), African Americans 46 (23%), others 33 (18%). Of the study population, 88 (43.8%) did not have a confirmed cancer diagnosis, of which we established a cancer diagnosis in 68 (77.3%) and ruled out cancer in 8 (4%). Of the 113 (56.2%) diagnosed at outside facilities, 63 (55.8%) were treatment naive and 22 (19.4%) had their cancer diagnosis revised. Of 175 patients which had staging information, 150 (85.7%) were stage 4. During the index admission, 45 (22.4%) patients had cancer-directed therapy. The average and geometric mean length of stay (days) for new patients was 12.1 and 8.8, respectively, compared to the established group of 8.2 and 6.1 (p &lt; 0.001). Inpatient mortality was higher in new patients (10.5% vs 6.8%, p &lt; 0.001) and they were more likely to be referred to hospice services (17.4% vs 8.3%, p &lt; 0.001). Furthermore, hospice referral was higher in the unestablished, previously treated group compared to treatment naive patients (28% vs 13.9%, p = 0.003), however inpatient mortality was similar (12% vs 9.9%, p = 0.63). ICU stay, 30-day readmission rate, discharge to home vs placement were similar in new and established patients (Table 1). Conclusions: Admitted new oncology patients typically present with advanced disease and had longer length of stay, mortality rates, and hospice referrals compared to established patients. Further research is needed to identify and improve care barriers to new inpatients, focusing on improving workflow process and timely goal concordant care discussions. [Table: see text]

Can initial apparent diffusion coefficient and tumour volume predict future metastases in treatment-naive patients with laryngeal squamous cell carcinoma

Can initial apparent diffusion coefficient and tumour volume predict future metastases in treatment-naive patients with laryngeal squamous cell carcinoma

Cabergoline targets multiple pathways to inhibit PRL secretion and increases stromal fibrosis.

Unravel the potential mechanism(s) of the on- and off-target actions of dopamine agonist therapy in both human prolactinoma tumors and neighboring stromal and immune cells. Five surgically resected prolactinomas (PRLomas) from 3 cabergoline (CBG)-treated patients and 2 treatment-naive patients were analyzed by using single-cell RNA sequencing (scRNA-seq) to compare the cellular composition and transcriptional landscape. Six major cell populations, namely tumor (88.2%), immune (5.6%), stromal (4.9%), progenitor cells (0.6%), proliferating cells (0.4%), and erythrocytes (0.2%), were observed. Tumor cells from CBG-treated patients expressed lower levels of genes that regulated hormone secretion, such as SCG2, VGF, TIMP1, NNAT, and CALD1, consistent with the inhibitory effects of CBG on hormone processing and secretion. Interestingly, we also observed an increased number of CD8+ T cells in the CBG-treated tissues. These cytotoxic CD8+ T cells expressed killing granule components such as perforin and the granzymes GZMB, GNLY, and KLRD1 as well as the inflammatory cytokine CCL5. Immune cell activation of these CD8+ T cells was further analyzed in a compartment-specific manner, and increased CD25 (IL2R) expression was noted in the CD8+ T cells from the CBG-treated samples. Additionally, and confirming prior reports, we noted a higher stromal cell population in the CBG-treated samples. Our scRNA-seq studies revealed key differences in the transcriptomic features of CBG-treated and CBG-untreated PRLomas in both tumor and microenvironment cellular constituents, and for the first time, describe the previously unknown activation of CD8+ T cells following CBG treatment, which may play a role in the tumoricidal actions of CBG.

#2691 Treatment naive membranous nephropathy patients treated with rituximab in COVID19 era

Abstract Background and Aims Standard of care of high-risk idiopathic membranous nephropathy patients is immunosuppressive treatment with cyclophosphamide and corticosteroids or rituximab. Our aim was to assess outcome and safety of rituximab therapy in COVID19 era in comparison to modified Ponticelli protocol. Method In this retrospective study all adult patients with biopsy proven membranous nephropathy treated with rituximab as a first line therapy from 2020 till 2022 were enrolled and compared with MN patients treated with modified Ponticelli protocol from 2013 till 2020. Renal outcome was defined as composite of partial and complete remission defined according KDIGO guidelines. Except otherwise stated, data are shown as N (%) or median with interquartile range (IQR) and accompanied p levels. Results During the COVID 19 era, between 2020 and 2022, 8 MN patients were treated with rituximab as a first line therapy. One was lost from follow up and one had allergic infusion reaction and therefore was excluded from further analysis. Ten patients were treated with modified Ponticelli protocol. There was no difference in age (60 vs. 59 years; p = 0.669), gender (M 57.1 vs. 60%), BMI (26.3 vs. 29.1cm/kg; p = 0.906), systolic (140. vs. 150 mmHg; p = 0.161) or diastolic (90 vs. 91.5 mmHg; p = 0.230) blood pressure between rituximab and cyclophosphamide treated group. Also, there was no difference in proteinuria between rituximab and cyclophosphamide treated group (16.2 (5.7–31.3) vs. 8.7 (6.5–12.5) g/dU; p = 0.201) Patients treated with cyclophosphamide had lower eGFR compared with patients treated with rituximab (51 (34-79) vs. 93 (72-98) ml/min/1,73 m²; p = 0.005). At 6 months follow up only 2 (28.6%) in rituximab group and 6 (60%) in cyclophosphamide group achieved outcome defined as composite of complete and partial remission. At one year follow up, there was no difference in outcome between groups and all patients from rituximab group compared to 8 patients (88.9%) from cyclophosphamide group accomplished composite favorable renal outcome (p = 398). At the end of follow up, one year after cyclophosphamide therapy eGFR was better (57 (43-96) vs. 51 (34-79) ml/min/1,73 m²). Rituximab was safe in our cohort. Three (50%) of patients acquired SARS CoV2 infection and there was no adverse outcome regarding COVID 19 disease. Conclusion Cyclophosphamide is faster than rituximab in accomplishing remission of nephrotic syndrome and improves deteriorated kidney function. Nevertheless, at 1 year follow up rituximab efficiency is proven to be excellent. Cyclophosphamide should be reserved for MN patients with nephrotic syndrome with reduced glomerular filtration rate.

Single-cell and spatial transcriptomics analysis of non-small cell lung cancer

Lung cancer is the second most frequently diagnosed cancer and the leading cause of cancer-related mortality worldwide. Tumour ecosystems feature diverse immune cell types. Myeloid cells, in particular, are prevalent and have a well-established role in promoting the disease. In our study, we profile approximately 900,000 cells from 25 treatment-naive patients with adenocarcinoma and squamous-cell carcinoma by single-cell and spatial transcriptomics. We note an inverse relationship between anti-inflammatory macrophages and NK cells/T cells, and with reduced NK cell cytotoxicity within the tumour. While we observe a similar cell type composition in both adenocarcinoma and squamous-cell carcinoma, we detect significant differences in the co-expression of various immune checkpoint inhibitors. Moreover, we reveal evidence of a transcriptional “reprogramming” of macrophages in tumours, shifting them towards cholesterol export and adopting a foetal-like transcriptional signature which promotes iron efflux. Our multi-omic resource offers a high-resolution molecular map of tumour-associated macrophages, enhancing our understanding of their role within the tumour microenvironment.

Inflammation-based markers, especially the uric acid/albumin ratio, are associated with non-dipper pattern in newly diagnosed treatment-naive hypertensive patients.

Physiologically, at night, blood pressure (BP) is expected to decrease by at least 10% in hypertensive individuals. The absence of this decrease, called non-dipper hypertension, is associated with increased end-organ damage and cardiovascular mortality and morbidity in hypertensive individuals. It is known that increased inflammatory process plays an important role in the etiopathogenesis of non-dipper hypertension pattern. In recent years, it has been shown that inflammation-based markers (IBMs) obtained by combining various inflammation-related hematological and biochemical parameters in a single fraction have stronger predictive value than single inflammatory parameters. However, until now, there has not been a study investigating the relationship of these markers with dipper/non-dipper status in newly diagnosed hypertensive patients. Based on ambulatory BP monitoring, 217 dipper and 301 non-dipper naive hypertensive subjects were included in this study. All subjects' IBM values were compared between dipper and non-dipper hypertensive individuals. IBMs [C-reactive protein/albumin ratio (CAR), monocyte/high-density lipoprotein cholesterol ratio (MHR), neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio, systemic immune-inflammation index (SII), uric acid/albumin ratio (UAR)] were significantly higher in the non-dipper group. CAR, MHR, NLR, SII, and UAR were determined as independent predictors for non-dipper pattern ( P < 0.05, for all). Also, UAR's diagnostic performance for non-dipper pattern was found to be superior to other IBMs (area under the curve: 0.783, 95% confidence interval: 0.743-0.822; P < 0.001). These findings suggest an association between elevated IBMs, particularly UAR, and the non-dipper hypertension pattern observed in our study.

Effectiveness of combined first-line medical treatment in acromegaly with prolactin cosecretion.

The aim of this study is to compare the response to first-line medical treatment in treatment-naive acromegaly patients with pure growth hormone (GH)-secreting pituitary adenoma (GH-PA) and those with GH and prolactin cosecreting PA (GH&PRL-PA). This is a retrospective multicentric study of acromegaly patients followed from 2003 to 2023 in 33 tertiary Spanish hospitals with at least 6 months of first-line medical treatment. Baseline characteristics, first-line medical treatment strategies, and outcomes were analyzed. We employed a multiple logistic regression full model to estimate the impact of some baseline characteristics on disease control after each treatment modality. Of the 144 patients included, 72.9% had a GH-PA, and 27.1% had a GH&PRL-PA. Patients with GH&PRL-PA were younger (43.9 ± 15.0 vs 51.9 ± 12.7 years, P < .01) and harboring more frequently macroadenomas (89.7% vs 72.1%, P = .03). First-generation somatostatin receptor ligand (fgSRL) as monotherapy was given to 106 (73.6%) and a combination treatment with fgSRL and cabergoline in the remaining 38 (26.4%). Patients with GH&PRL-PA received more frequently a combination therapy (56.4% vs 15.2%, P < .01). After 6 months of treatment, in the group of patients under fgSRL as monotherapy, those patients with GH&PRL-PA had worse control compared to GH-PAs (29.4% vs 55.1%, P = .04). However, these differences in the rate of disease control between both groups disappeared when both received combination treatment with fgSRL and cabergoline. In GH&PRL-PA, the biochemical control achieved with fgSRL as monotherapy is substantially worse than in patients harboring GH-PA, supporting the inclusion of cabergoline as first-line medical treatment in combination with fgSRLs in these subgroups of patients.

The impact of Vitreo-Macular interface abnormalities on the response to Anti-VEGF therapy for centre involving diabetic macular oedema.

The influence of Vitreomacular Interface Abnormalities (VMIA) such as Epiretinal Membrane (ERM) and/or vitreomacular traction (VMT) on the response of patients with Centre Involving Diabetic Macular Edema (CIDME) to standard of care Anti-VEGF medications is under-researched. The aims of this study were: 1) To determine the incidence of VMIA at baseline and 12 months amongst treatment naive patients commencing anti-VEGF treatment 2) To compare the response to Anti-VEGF medications at 3 monthly intervals for 12 months in a large cohort of patients with and without VMIA on their baseline OCT scan. Response was determined in terms of: number of injections, central macular thickness and visual acuity. A retrospective case notes review of treatment naïve patients with newly diagnosed CIDME. Included patients had been commenced on intravitreal Anti-VEGF injections (ranibizumab or aflibercept) at a single centre. Inclusion criteria were: treatment naïve DME patients with a CMT of 400μ or more receiving anti-VEGF treatment with at least 12 months follow up and in whom macular OCT scans and visual acuity (VA) measurements were available within two weeks of baseline, 3, 6, 9 and 12 months. Exclusion criteria included: previous intravitreal therapy, previous vitrectomy, cataract surgery during the follow-up period, concurrent eye conditions affecting vision or CMT. 119 eyes met the inclusion criteria and underwent analysis. Groups were comparable in their baseline demographics. Baseline CMT measurements were comparable at baseline (417μ and 430μ in the No-VMIA and VMIA groups respectively) and improved to approximately 300μ in both groups. From 6 months CMT continued to improve in the no-VMIA while progressively deteriorating in the VMIA group. Change in CMT was statistically different at 12 months between the 2 groups (108μ and 79μ, p= 0.04). There was a mean of 7 injections after 12 months. Our study has shown a 46% incidence of VMIA amongst patients newly diagnosed with centre involving DME undergoing treatment with anti-VEGF injections. We have also demonstrated a significant difference in CMT and VA response to anti-VEGF treatment in patients with and without VMIA. Initial response was similar between the 2 groups up until 6 months. From 6 to 12 months significant differences in treatment response emerged. Differences in clinical response between patients with and without VMIA may help guide further prospective controlled studies and optimise treatment strategies.

Exhaled breath analysis in patients with potentially curative lung cancer undergoing surgery: a longitudinal study

Exhaled breath analysis has emerged as a non-invasive and promising method for early detection of lung cancer, offering a novel approach for diagnosis through the identification of specific biomarkers present in a patient’s breath. For this longitudinal study, 29 treatment-naive patients with lung cancer were evaluated before and after surgery. Secondary electrospray ionization high-resolution mass spectrometry was used for exhaled breath analysis. Volatile organic compounds with absolute log2 fold change ⩾1 and q-values ⩾ 0.71 were selected as potentially relevant. Exhaled breath analysis resulted in a total of 3482 features. 515 features showed a substantial difference before and after surgery. The small sample size generated a false positive rate of 0.71, therefore, around 154 of these 515 features were expected to be true changes. Biological identification of the features with the highest consistency (m/z −242.18428 and m/z −117.0539) revealed to potentially be 3-Oxotetradecanoic acid and Indole, respectively. Principal component analysis revealed a primary cluster of patients with a recurrent lung cancer, which remained undetected in the initial diagnostic and surgical procedures. The change of exhaled breath patterns after surgery in lung cancer emphasizes the potential for lung cancer screening and detection.