Line Treatment For Patients Research Articles

Safety and efficacy of Levorag emulgel in the treatment of anal fissures using a validated scoring system.

Anal fissure is one of the most common anal disease characterized by intense anal pain, and deterioration of patients quality of life. Treatment is mainly based on the topical administration of calcium antagonist or nitric oxide ointments, and in cases refractory to medical treatment patients can undergo surgery. This study aims to assess the efficacy and safety of Levorag emulgel in the treatment of acute and chronic fissures using of a validated scoring system. A prospective observational study was carried out on patients with anal fissures between February and May 2022. The efficacy of the treatment was evaluated using the REALISE score, a new validated scoring system that rates VAS for pain, NSAID use, pain duration, bleeding, and quality of life (QoL), recorded after 10, 20 and 30 days from the beginning of treatment. Forty patients (median age 46 years, IQR 29-57, 70% women) with acute (22, 55%) or chronic (18, 45%) anal fissures entered the study. The median anal pain score according to the VAS scale decreased significantly from 7 (IQR 4.7-8) at baseline to 1 (IQR 0-3.2, p = 0.05) after 20 days. At the 30-day proctological examination, 22 patients (61%) were pain free (median VAS of 0, IQR 0-1.2, p < 0.05). Pain duration after defecation measured according to the REALISE score, showed a significant decrease after 10 days, from a median value of 2 (IQR 1-4) to 1 (IQR 1-1.2) (p < 0.005). The median value of the REALISE score decreased significantly, from 15 (IQR 11-19.25) at first proctological evaluation to 4 (IQR 4-6, p = 0.139) after 30 days of treatment. At day 30, complete fissure healing was achieved in 30 patients (80%). The healing rate was 82% and 78% in patients with acute and chronic anal fissures, respectively. The use of Levorag® Emulgel may represent a safe and effective non-invasive first line treatment in patients affected by acute or chronic anal fissure.

The Role of Conservative Management in the Avascular Necrosis of the Femoral Head: A Review of Systematic Reviews.

Multiple medical and surgical treatments have been described in the early stages of Avascular Necrosis (AVN) of the femoral head which delay the disease progression. Similarly, multiple studies, trials, reviews, and systematic reviews exist for the various treatments described and their outcomes but with no consensus over which is superior. So in this study, we reviewed the systematic reviews of all the conservative therapies for AVN of the femoral head systematically to identify a single or a combination of non-surgical treatment choices in the initial stages of the disease. A thorough literature search has been carried out in January 2022 through the use of Pubmed, EMBASE, and Cochrane electronic databases using PRISMA guidelines. The Mesh words and Keywords used were "femoral head AVN", "Conservative management", and "Systematic Reviews". The inclusion criteria used during the screening were, any systematic reviews which included patients with AVN either idiopathic or secondary, who are managed with conservative therapies like bisphosphonates, Hyper Baric Oxygen Therapy (HBOT), Shock wave therapies like Extracorporeal Shock Wave Therapy (ESWT), or electrical therapy like Pulsed Electro Magnetic Field (PEMF). The quality of the included systematic reviews was assessed using AMSTAR-2 criteria. The initial search yielded 364 studies which on screening based on our inclusion criteria finally resulted in seven systematic reviews to be included in the present study. There were two systematic reviews for Hyper Baric Oxygen Therapy (HBOT), two for Extracorporeal Shock Wave Therapy (ESWT), one for electrical stimulation modalities like Pulsed Electro Magnetic Field (PEMF), and two for bisphosphonates. The follow-up of the patients in the included systematic reviews varied from 6weeks to 10years. The total number of patients varied from 77 to over 1000 across the systematic reviews. Almost all of the studies included a control group that either received the intended treatment with adjuncts or did not receive any treatment at all. Because of the heterogeneous nature of included articles in the systematic reviews, meta-analysis was performed in only three of the included systematic reviews. Of all the modalities of treatment described, bisphosphonates are easily available and cost-effective and do not require any hospital resources/machinery for delivering the treatment. So they can be used as an initial line of treatment for patients with early stages of AVN (Ficat and Arlet 1-3) and based on the hospital availability of resources could be supplemented with any of the biophysical modalities (ESWT/PEMF/HBOT) for maximum efficacy to delay the disease progression. Systematic review. The online version contains supplementary material available at 10.1007/s43465-023-00818-5.

In Vivo Efficacy Testing of Peptide Receptor Radionuclide Therapy Radiosensitization Using Olaparib.

Peptide receptor radionuclide therapy (PRRT), a form of internal targeted radiation treatment using [177Lu]Lu [DOTA0-Tyr3]octreotate, is used to treat patients with metastasized neuroendocrine tumors (NETs). Even though PRRT is now the second line of treatment for patients with metastasized NETs, the majority of patients will not be cured by the treatment. PRRT functions by inducing DNA damage upon radioactive decay and inhibition of DNA damage repair proteins could therefore be used as a strategy to potentiate PRRT. Previous work has shown promising results on the combination of PRRT with the PARP inhibitor olaparib in cell lines and mice and we have been taken the next step for further in vivo validation using two different xenografted mouse models. We observed that this combination therapy resulted in increased therapeutic efficacy only in one model and not the other. Overall, our findings indicate a tumor-type dependent anti-tumor response to the combination of PRRT and olaparib. These data emphasize the unmet need for the molecular stratification of tumors to predetermine the potential clinical value of combining PARP inhibition with PRRT.

A phase1b study of navicixizumab plus FOLFIRI in second-line treatment of patients with metastatic colorectal cancer.

111 Background: Navicixizumab is an anti-delta-like ligand 4 (DLL4)/vascular endothelial growth factor bispecific antibody which has shown promising preclinical and clinical activity in multiple tumor types. The blockade of DLL4, a transmembrane protein acting as a ligand for Notch receptors 1 and 4, causes tumor differentiation and reduction in cancer stem cells, as well as repolarization of the tumor microenvironment. Methods: We conducted a phase 1b single-arm dose escalation study combining navicixizumab with FOLFIRI or FOLFOX as second line treatment for patients with metastatic colorectal cancer (CRC). Patients were dosed either at 3 or 4 mg/kg intravenously once every 2 weeks (Q2W). The primary endpoint was the maximum tolerated dose of navicixizumab in combination with FOLFOX or FOLFIRI. Results: Between December 2016 and August 2018, 15 patients received navicixizumab plus FOLFIRI. Median patient age was 55 years, and nine of 15 patients were female (60%). Three patients were enrolled in the 3 mg/kg dose-escalation cohort, 2 patients were enrolled in the 4-mg/kg dose-escalation cohort, and 10 patients were enrolled in the 3 mg/kg dose expansion cohort. No DLTs were observed in this study. The median duration of navicixizumab therapy was 127 days. Hypertension was the most frequent all-grade treatment-related adverse event reported (12 of 15 patients, 80%), followed by fatigue (8 of 15 patients, 53.3%). Grade 3 hypertension was reported in 3 patients (20%). Eight of the 15 patients (53.3%) experienced at least one serious adverse event, resulting in discontinuation of study for 6 (40%) patients. One patient had a bowel perforation. One patient (3 mg/kg cohort) experienced a treatment-related grade 5 cardiopulmonary arrest resulting in death. The best overall response was partial response in three patients (20%). Eleven patients (73.3%) had stable disease and one (6.7%) experienced disease progression. Conclusions: This study was stopped early to focus on the development of navicixizumab in ovarian cancer. Although the disease control rate was promising, further evaluation is needed to determine whether navicixizumab delivers efficacy greater than chemotherapy alone and assess tolerability of this regimen. [Table: see text]

A multicenter retrospective cohort study evaluating the clinical significance of CA125 in later line of patients with metastatic colorectal cancer.

253 Background: The peritoneal dissemination is one of the metastatic forms of gastrointestinal cancer and has a poor prognosis. It has been reported that the presence of CA125 in mesothelial cells lining the peritoneum is involved in the elevation of CA125 due to peritoneal dissemination and inflammation of cancerous ascites, and CA125 may be a useful predictor of peritoneal dissemination in gastrointestinal cancer. It has also been reported that CA125 correlates with ascites volume and prognosis. However, there are no reports evaluating the clinical significance of CA125 in the later line of metastatic colorectal cancer (mCRC). Therefore, we conducted a multicenter retrospective study. Methods: We retrospectively analyzed the clinical data of 121 patients who received trifluridine/tipiracil (FTD/TPI) or Regorafenib from January 2012 to May 2018 in 10 centers and had the result of serum CA125 just before the treatment. Patients who had received either FTD/TPI or Regorafenib were excluded. In this study, the levels of ascites were classified as follows: "none" as undetectable by computed tomography scanning, "mild" as confined to the pelvic cavity or upper abdomen, "severe" as continuous from the pelvic cavity to the upper abdomen, and "moderate" as between "mild" and "severe". RECIST ver.1.1 was used for analysis of tumor response. Survival analyses were performed with Kaplan-Meier method, log-rank test and Cox proportional hazards model. Results: There were 75 patients in the baseline CA125 normal group (group N) and 46 patients in the high group (group H). ECOG PS tended to be worse in group H than in group N (ECOG PS (0/1/2) 26/43/6 and 9/28/9 in N and H groups, p=0.076). There were significantly more patients with ascites in group H than in group N (Yes/No 7/68 and 26/20 in N and H groups, p&lt;0.001). Furthermore, ALP, CRP, CA19-9 and NLR were significantly higher, and Alb was significantly lower in group H than in group N. Baseline CA125 correlated with baseline ascites volume (p&lt;0.001). PFS and OS were significantly shorter in group H compared to group N (PFS; 1.9 vs. 3.0 months; HR 1.576 [95%CI 1.081-2.299]; p=0.016, OS; 4.1 vs. 11.0 months; HR 2.418 [95%CI 1.634-3.576]; p&lt;0.001). The rate of change for CA125 was significantly higher in patients with progressive disease on first evaluation CT compared to patients with disease control (p=0.002), and PFS and OS were significantly shorter in the increased CA125 group measured first after treatment than in the non-increased CA125 group (PFS; 1.9 vs. 4.6 months; HR 3.104 [95%CI, 2.004-4.809]; p&lt;0.001, OS; 5.9 vs. 13.0 months; HR 2.199 [95%CI, 1.474-3.282]; p&lt;0.001). Conclusions: In this retrospective analysis, baseline CA125 correlated with ascites volume in later line treatment of patients with mCRC, suggesting that increased CA125 may be a predictive and prognostic factor. Clinical trial information: UMIN000040059 .

The Endovascular Options For Management of Superficial Femoral Artery Osteal Occlusions

Background: Endovascular intervention is now the primary line of treatment for patients with critical limb ischemia.Nevertheless, endovascular experts face several obstacles with these treatments due to the existence of broad multilevellesions, osteal lesions, and lengthy and entire chronic occlusive lesions.Aim of this work: Evaluation the different endovascular techniques of management the superficial femoral arteryosteal lesions in cases with critical limb ischemia or incapacitating claudication.Patients and Methods: This is a prospective study of 55 patients who presented to Beni Suef University Hospitals’vascular surgery unit between January 2020 and December 2021. Patients with symptomatic atherosclerotic occlusivedisease of the osteal region of SFA are included in the research.Results: Technical success was done in 92.7% of cases. Figure (4) shows that;the mean hospital stay of cases in thisstudy was 1.53 ± 0.81 days with range (1.0 – 4.0).Follow up at 1 and 3 months revealed that; patency was kept in 51(100%), 49 (96.07%) and 40 (78.43%) of all technical successful cases in one, three and six months respectively.Conclusion: Endovascular treatments show promising prospects as treatment options for SFA atherosclerotic occlusivedisorders, particularly when osteal lesions are present. Endovascular intervention techniques, facilities, and expertisehave greatly improved, resulting in a high technical success rate and a high proportion of lower limb patency in CLIpatients.

Romiplostim and immunosuppressive therapy as first line treatment in patients with aplastic anemia

Romiplostim and immunosuppressive therapy as first line treatment in patients with aplastic anemia

Benefit of extracorporeal membrane oxygenation in myocardial infarction-induced cardiogenic shock.

Extracorporeal membrane oxygenation (ECMO) is frequently used for emergency support in patients with profound cardiogenic shock (CS) of all etiologies. However, no controlled study investigating ECMO in myocardial infarction (AMI)-induced CS is available. Retrospective analysis of patients experiencing AMI induced CS; ECMO therapy vs. non ECMO therapy. A total of 476 patients with AMI-induced CS were investigated. One hundred twenty-seven patients (26.7%) received emergency veno-arterial ECMO support, 349 patients did not receive ECMO support. Patients were propensity score matched based on relevant clinical and laboratory factors and revealed 127 matched pairs. Mean age of patients was 65.0±12.3 years and mean Syntax score was 25.9±7.3 in the full unmatched patient population. Survival at 1, 3 and 5 years after CS was 45.6%, 43.5%, and 41.3% in the ECMO group and 17.4%, 15.8%, and 14.9% in the full unmatched control group (log-rank: P<0.001). After propensity score matching, 1-, 3-, and 5-year survival was 14.4%, 13.5%, and 11.2% in the matched control group (P<0.001). Cox regression analysis identified ECMO support (HR: 2.57; 95% CI: 1.89-3.50; P<0.001) and completeness of revascularization (HR: 1.89; 95% CI: 1.74-2.34, P=0.003) to be independent predictors for long term survival. Extracorporeal life support by ECMO significantly increased survival in patients with AMI-induced CS. ECMO insertion increased survival probability 2.57-fold and should be considered as first line treatment in patients with profound AMI-induced CS.

Efficacy and Safety of First-Line Targeted Treatment and Immunotherapy for Patients with Biliary Tract Cancer: A Systematic Review and Meta-Analysis.

Biliary tract cancer is one of the most aggressive and fatal tumours. Gemcitabine with cisplatin chemotherapy has long been the first-line treatment, but the prognosis is poor. In recent years, targeted treatment and immunotherapy have produced encouraging outcomes requiring a thorough review and meta-analysis. For this systematic review and meta-analysis, we searched four databases, starting from the inception dates of databases to 11 January 2022. This study comprised randomised clinical trials and cohort studies that used immunotherapy or targeted treatment as the first line of treatment for patients with biliary tract cancer. From the 888 studies extracted, 33 trials were examined and found to meet the criteria. These included 3087 patients, 16 single-arm trials, 13 RCTs, one nRCT, a prospective single-arm pilot study, and a clinical setting in the real world. From 2010 to 2020, 33 studies were conducted using targeted treatment or immunologic therapies as first-line treatments for BTC patients, and 18 of those studies had positive outcomes. This study demonstrates that immunotherapy combined with chemotherapy as first-line treatment can provide survival benefits by improving the objective response rate for patients with unresectable biliary tract cancer. The potential for combination therapy to become a new trend in clinical treatment is promising but needs further clinical evaluation.

Overall survival of patients with metastatic KRAS wild type colorectal cancer patients treated with anti-EGFR third line monotherapy

Introduction. There is no evidence-based data comparing upfront chemotherapy doublets with anti-EGFR monoclonal antibody with sequential treatment utilizing anti-EGFR monotherapy as a consecutive line of treatment in patients with metastatic colorectal cancer. Here we report real-world survival data for patients with colorectal cancer (CRC) treated with anti-EGFR monoclonal antibody as 3rd line monotherapy. Material and methods. It was single center retrospective study. We collected retrospectively data of wild-type KRAS metastatic CRC patients who have failed oxaliplatin- and irinotecan based therapy and were treated with anti-EGFR monoclonal antibody as the 3. line monotherapy in 2009–2017 in Copernicus Memorial Hospital, Lodz, Poland. Last observation was recorded in February 2020. We calculated median overall survival (since commencement of palliative systemic treatment), median progression free survival and median OSIII (overall survival sine commencement of monotherapy with anti-EGFR agent). Results. 130 patients were included in the study. 40.6% were females. The median age was 63 years (range 38–83). 57% of patients were initially diagnosed with metastatic/inoperable colorectal cancer. 80 patients were treated with 3. line cetuximab, 50 — with panitumumab. At the moment of data analysis 123 deaths were recorded. OS since start of palliative systemic treatment was calculated for 120 patients and its median was 25.8 months. MPFS since start of anti-EGFR antibody was 4.3 months, mOSIII —10.7 months. Conclusions. 3rd line treatment of metastatic colorectal cancer with anti-EGFR antibodies is effective. It is good option for patients, who are not fit enough or not willing to have 1st line triplet therapy.

Endoscopic Surveillance and Treatment of Upper GI Tract Lesions in Patients with Familial Adenomatous Polyposis—A New Perspective on an Old Disease

Familial adenomatous polyposis (FAP) is an autosomal dominant disease caused by a germline mutation in the adenomatous polyposis coli (APC) gene. Patients with FAP develop up to thousands of colorectal adenomas as well as lesions in the upper GI tract. In FAP, the upper digestive lesions include gastric fundic gland polyps (FGPs), antrum adenomas, duodenal or small intestinal adenomas, and carcinoma. Patients, after colectomy, are still at significant risk for extracolonic malignancies. Advances in endoscope resolution and optical enhancement technologies allow endoscopists to provide assessments of benign and malignant polyps. For this reason, in the past decades, endoscopic resection techniques have become the first line of treatment in patients with polyps in the upper GI, whereby polyps and even early cancers can be successfully cured. In FAP patients, endoscopic ampullectomy appears to be a safe and effective way of treating patients with ampullary tumors. According to current indications, endoscopic retrograde cholangiopancreatography (ERCP) and stenting of the main pancreatic duct follow ampullectomy.

Efficacy of ustekinumab, vedolizumab, or a second anti-TNF agent after the failure of a first anti-TNF agent in patients with Crohn’s disease: a multicentre retrospective study

BackgroundNo study has performed a face-to-face comparison of biologics after the failure of the first anti-TNF agent in patients with Crohn’s disease (CD). The aim of the study was to compare the efficacy of biologics in this setting.MethodsPatients with CD who were refractory to a first anti-TNF agent, and treated with ustekinumab (UST), vedolizumab (VDZ), or a second anti-TNF drug as a second-line biological agent at 10 French tertiary centres from 2013 to 2019 were retrospectively included in this study.ResultsAmong the 203 patients included, 90 (44%) received UST, 42 (21%) received VDZ and 71 (35%) received a second anti-TNF agent. The first anti-TNF agent was discontinued due to a primary nonresponse in 42 (21%) patients. At weeks 14–24, the rates of steroid-free remission were similar between the UST, VDZ and second anti-TNF groups (29%, 38% and 44%, respectively, p = 0.15). With a mean follow-up of 118 weeks, drug survival was shorter for patients who received ustekinumab treatment (p = 0.001). In the case of trough level less than 5 µg/ml, patients treated with a second anti-TNF agent had a higher postinduction remission rate (p = 0.002), and drug survival (p = 0.0005). No other relevant factors were associated with treatment efficacy, including trough levels greater than 5 µg/ml.ConclusionsVDZ, UST and a second anti-TNF agent exhibit similar efficacy in the short term, as second-biological line treatment in patients with CD who are refractory to a first anti-TNF agent, but shorter drug maintenance is observed for patients treated with UST.

Real-World Data Analysis of the Molecular Response Kinetics within the Two First Years of the RELMC-NOVA Study in Newly Diagnosed Spanish CML-CP Patients Treated with Tirosin Kinasa Inhibitors (TKIs) in First Line

Introduction: The RELMC-Nova study analyses first line treatments in patients with chronic myeloid leukemia (CML) in chronic phase (CP) in standard clinical practice in two cohorts, before (retrospective) and after (prospective) the introduction of generic imatinib in 25 hospitals throughout Spain with special emphasis on the molecular kinetics of the initial response (studied as halving time [HT] and with logarithmic reduction [log red] between 2 times). METHODS: 311 patients were registered (171 in the retrospective cohort and 140 in the prospective cohort), all of them treated with TKIs according to standard clinical practice. Molecular Response (MR) was analyzed at 3, 6, 12, 18 and 24 months of treatment in local laboratories according to local clinical practice. HT and log red were calculated between diagnosis and molecular response at 1, 2, 3 and 6 months. RESULTS:Clinical characteristics at diagnosis: total (retrospective (R)/prospective(P)) were the following: Median age 56 years (55/61), Body mass index 24.2 (24.2/24.2), Male-Female 58%-42% (56%-44%/60%-40%), Sokal Index (L-I-H) 44%-43%-13% (50%-37%-13%/37%-51%-12%) and ELTS (L-I-H) 57%-33%-10% (63%-30%-7%/50%-37%-13%). First line TKI: Imatinib (GlivecÒ): 35% (65%/0%), generic Imatinib: 34% (0%/75%), 2nd generation (2nd G) TKIs 30.3% (35%-25%): Nilotinib 20% (22%/17%), Dasatinib 10% (13%/7%), Ponatinib 0.3% (0%/1%). In the retrospective cohort 26.3% of Low o Intermediate Sokal Index patients were treated with 2nd GTKIs versus only 18.2% in the prospective cohort. Overall response rate, total (R/P): See table 1. A statistically significance difference in major molecular response (MMR) between the retrospective and prospective cohorts was only seen at 3 months. Deep molecular response (>MR4), total (R/P): See table 1. No statistically significant differences were observed between cohorts at any time point. Overall response rate, total (Imatinib/2nd GTKIs): See table 1. A statistically significance difference in MMR between imatinib and 2nd GTKIs was only seen at 3 months. Deep molecular response (>MR4), total (Imatinib/2nd GTKIs): See table 1. No statistically significant differences were observed between cohorts at any time point. Only 1 patient (0.32%) showed progression to accelerated phase. Response kinetics: See table 1. Halving time at 3 and 6 months was lower in patients treated with 2nd GTKIs, but without statistical significance. Patients with deep molecular response at 24 months showed a lower HT being statistically significant only at 6 months. Log red: No significant differences were found between patients treated with imatinib and 2nd GTKIs, although results were initially higher in patients treated with 2nd GTKIs. Patients with a deep molecular response at 24 months showed statistically significant differences in log reduction at 3 and 6 months. CONCLUSIONS: 1. Generic imatinib has cornered 1st line treatment increasing from 65% to 75% in the retrospective and prospective cohorts respectively, relegating 2ndGTIKs to high-risk patients. 2. The responses obtained in the first months were higher and faster with the 2nd GTKIs but evened out after 12 months and remained similar at 2 years. 3. Molecular response kinetics (HT or log red) can predict future response and should be assessed in patients with poor early responses. 4. A rapid decline (HR or log red) at the start of treatment guarantees a deep response at 2 years. 5. 2nd GTKIs produce faster molecular response kinetics but final outcomes were similar to that obtained with imatinib. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Fludarabine, Cyclophosphamide and Rituximab (FCR) As First Line Treatment in Patients with Chronic Lymphocytic Leukemia (CLL): A Long-Term Analysis of the German CLL Study Group (GCLLSG) Registry

Introduction: Large randomized trials investigating targeted agents have resulted in a markedly improved progression-free survival (PFS) when compared to standard chemoimmunotherapy. However, for small subgroups with a favorable risk profile, overall survival was not consistently superior for targeted agents. Long-term follow up on FCR suggested that favorable risk patients (pts) benefit significantly from this therapy and can expect an exceptionally long PFS. In addition, targeted first line (1L) therapies for favorable risk pts are reimbursed only in a minority of countries. Here, we report long-term efficacy data of FCR treatment obtained from pts documented within the GCLLSG registry. Methods: Documentation within the GCLLSG registry started in 2013 and included both pts from prospective trials (29.7%), most importantly of the CLL8 trial (22.6%) and CLL10 trial (62.1%) as well as retrospective data. Pts with confirmed diagnosis of CLL who received FCR as 1L treatment were included. Patient characteristics were reported in median, interquartile ranges or frequencies and percentages. Response was reported as response or non-response. Event-free survival (EFS), which was defined as the time from start of (first) FCR treatment to disease progression, initiation of subsequent treatment for CLL or death. EFS was chosen as an endpoint for this report due to concerns that PFS might give unrealistically good results due to lack of documentation. However, PFS and TTNT data will be presented at the meeting. Overall survival was calculated from initiation of 1L treatment for all pts who received 1L treatment after 2013. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated by Cox proportional hazards regression. Variables that were significantly associated with EFS in univariate analyses (significance level was set at 5%) were considered as candidates for the multivariate modelling to identify independent prognostic risk factors. Results: As of September 2021, a total of 5922 pts were enrolled in the registry of which 417 received FCR as 1L treatment between 2003 and 2021. 223 pts (53.5%) received treatment before 2013 and 194 (46.5%) after 2013. Median observation time from 1L treatment was 95.8 (interquartile range 58.7-126.8) months. Patient characteristics showed a median age of 58 (range 24-83) years. Unmutated IGHV (U-CLL) was present in 61.4% of the pts. Regarding genomic aberrations based on the hierarchical model, del(17p) was found in 1.9%, del(11q) in 15.2%, trisomy12 in 15.5%, mono-allelic del(13q) in 34.3% and none of these changes in 33.0% of the pts. 88.8% of the pts responded to first line therapy, 11.2% were documented as non-responder. Median EFS was 71.1 month, for 188 pts no event was documented at the time point of data cut-off. Age group (≤ 65 years, >65 years), del(11q), IGHV mutational status, TP53 status, and serum thymidine kinase (TK) were associated with EFS in univariate analyses. Overall, 116 pts with 67 events were included in the final multivariable model for EFS. U-CLL (HR 1.949 (95%CI: 1.170-3.247; p=0.010) and TK >10 U/l (HR 2.107 (95%CI: 1.153-3.849; p=0.015) were independent adverse prognostic risk factors for EFS. When low TK and M-CLL were combined, the median EFS was not reached, with a 5-year survival rate of 95.8%. In contrast, median EFS was 84.1 months for pts with U-CLL and high TK. In U-CLL pts, median EFS was 87.0 months for pts with TK ≤ 10 U/l, and 58.9 months for pts with TK > 10 U/l. Median overall survival was not reached with a 5-year survival rate of 92.7%. Conclusion: Within this cohort of pts with a long follow up in the GCLLSG registry, FCR treatment was associated with a long EFS especially in pts with a low risk profile exhibiting a mutated IGHV status und low TK. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Obinutuzumab Plus Chemotherapy As First Line Treatment in Patients with Follicular Lymphoma: Experience from a Community Hospital

Background The combination of Obinutuzumab plus chemotherapy (Obi-chemo) regimen is currently one of the standard first-line treatments available for patients diagnosed with follicular non-Hodgkin's lymphoma (FL). The aim of our study is to evaluate the efficacy and safety of the Obi-chemo regimen in a community hospital setting. Methods Retrospective analysis of patient's medical records admitted to our hospital with a confirmed pathologic diagnosis of FL that were treated with the regimen of Obi-chemo as first-line treatment. Between January 1, 2017 and January 5, 2022, a total of 10 consecutive patients met the criteria for evaluation. Results The baseline characteristics of the patients evaluated are as follows: The group consisted of 7 males and 3 females. Median age in years was 56 (range 43-80). 10% (n=1) patients had stage 2, and the remaining 90% (n=9) had stage III-IV. Bone marrow involvement was noted in 70% (n=7) and 40% (n=4) had bulky mass >7 cm at presentation. Of the total ten patients, 60% (n=6) received Obinutuzumab plus Bendamustine and the remaining 40% (n=4) received Obinutuzumab plus CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone). All patients required G-CSF support. After completion of chemotherapy, 7 patients achieved a complete clinical and radiologic remission whereas 3 patients achieved a partial remission. Of these last 3 patients, two went on to achieve a complete remission during follow-up. Of the 7 patients who achieved an initial complete remission, one subsequently did relapse during follow-up. While on treatment, neutropenia and thrombocytopenia were documented in all 10 patients. 40% (n=4) of patients developed neutropenic fever, and 10% (n=1) developed grade 3 thrombocytopenia. 50% (n=5) of patients developed grade 1-2 infusion-related adverse events (nausea, hypertension, headache and skin rash). Two patients required chemotherapy de-escalation due to toxicity. No long-term toxicity or treatment-related deaths were reported. Conclusions Our study supports the findings of the pivotal clinical trials that led to the approval of the Obi-chemo antineoplastic regimen as first-line treatment for patients with FL by the regulatory agencies in Europe (EMA) and North America (FDA).

Discontinuation of Thrombopoietin Receptor Agonists: A 10 Year Real-World Experience from an Academic Hospital in Madrid

Background: Thrombopoietin receptor agonists (TPO-RAs) have become the second line treatment for patients with immune thrombocytopenia (ITP). Despite TPO-RAs are currently indicated for continuous treatment, some patients can achieve a sustained response that allows tapering and discontinuation. Predictors of responses and relapses after discontinuation are unknown factors that are being under investigation. Methods: This is a retrospective study approved by Hospital Universitario La Paz Ethical Committee. We describe our experience during 10 years in discontinuation of TPO-RAs and relapses in the ITP patient cohort from Hospital Universitario La Paz in Madrid.We included all ITP patients treated with TPO-RAs between 1st January 2011 and 31st December 2020. We analyzed response, discontinuation, and relapses after TPO-RAs treatments, with a follow-up period until 31st December 2021. This research was funded by ISCIII-Fondos FEDER PI19/00772 and Platelet Disorder Support Association. Results: One-hundred-fifty-one ITP patients were treated with TPO-RAs between 1st January 2011 and 31st December 2020. We excluded those without complete information about response, discontinuation, and relapses after TPO-RAs, analyzing a total of 133 patients. Thirteen received Romiplostim, 7 men and 6 women, with a median age of 66y (range 3-98). All of them achieved a clinical response according to standard criteria and in 4 it was possible to discontinue TPO-AR, with no need of retreatment with a median follow-up of 17,4 months (13,6-39,5). Seventy-five patients were treated with Eltrombopag, 33 men and 42 women, with a median age of 49y (range 1-98). Seventy-one patients get a clinical response, which allows discontinuation of TPO-AR in 43 of them, with 25 sustained responses and a median follow-up of 40,5 months (9,9-60,3). We also included 45 ITP patients, 21 men and 24 women, median age of 53y (range 2-93), who received both TPO-AR because of lack of response or intolerance with the first (4 Romiplostim and 41 Eltrombopag). Among the 34 patients who achieved a response, 17 were able to discontinue TPO-ARs and 7 needed retreatments. The follow-up period for this cohort was 23,4 months (1,9-75). Globally, 39 patients discontinue TPO-RAs with no need of further ITP treatment with a median follow-up of 28,4months (1,9-75) since discontinuation until the end of the study.Results are summarized in Table 1. Conclusion: In conclusion, 29% (39/113) of ITP patients who were treated with TPO-RAs could discontinue this treatment without relapses with a median follow-up of 28,4months (1,9-75) since discontinuation. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

ODP224 Metformin Associated Lactic Acidosis in a Nondiabetic Young Female

Abstract Background Metformin is the first line of treatment for patients with Diabetes Mellitus type 2. Despite multiple benefits, metformin is contraindicated in stage 4 renal disease due to an increased risk of metformin associated lactic acidosis (MALA). MALA is estimated to have a high mortality rate of 30-50%. The presentation of MALA can mimic sepsis and organ failure. Clinical Case We report a case of a 32 year old female who presented with generalized weakness and shortness of breath. She was found to have severe metabolic acidosis (PH 7. 04, PCO2 40 mmHg, Bicarb 15 mmol/L, anion gap 14 mmol/L, lactic acid 8.7 mmol/L), hypotension (82/46 mmHg), pancytopenia, moderate transaminitis, severe acute kidney injury (creatinine 3.2 mg/dL, GFR 17 mL/min/1.73 m2), and profound hypoglycemia (serum glucose 42 mg/dL). Endocrinology was consulted due to hypoglycemia and suspected adrenal insufficiency. During the encounter the patient was alert and oriented, but reported severe nausea and appeared in significant distress. On review of medications, she reported taking phentermine and metformin for weight loss, hydrochlorothiazide for hypertension, and fluoxetine for depression. She denied taking other supplements. She denied any history of diabetes mellitus or prediabetes. Computed tomography (CT) of the chest and abdomen were unremarkable. The patient's potassium was normal. Lactic acidosis continued to increase (16.1 mmol/L) despite intravenous fluids, empiric broad spectrum antibiotics, and stress dose steroids. Approximately 19 hours after the arrival, she underwent dialysis due to suspected MALA. Her lactic acid improved after dialysis transiently (6.1 mmol/L), but later worsened again (11.3 mmol/L). Urine and blood cultures returned positive for Klebsiella Pneumoniae (pan-sensitive). She was treated appropriately for sepsis since presentation to the emergency room, but her clinical condition (and lactic acid) continued to deteriorate. On the second day of admission, the patient developed respiratory failure requiring intubation and mechanical ventilation. Her hypotension persisted and she required multiple pressors. Sustained low-efficiency dialysis was restarted due to worsening of metabolic acidosis. Patient then became unresponsive on hospital day 4. Sedation was stopped and CT of the brain revealed significant edema and mild bilateral subarachnoid hemorrhage. Patient was confirmed brain dead by perfusion study. Conclusion This case illustrated a constellation of factors that led to a poor outcome. Off label use of metformin for weight loss, late diagnosis of acute severe renal failure, and delayed diagnosis of MALA all contributed to the poor outcome in this patient. Even though MALA has a relatively low estimated incidence rate, this case emphasizes the importance of medication reconciliation and the need for recognition that MALA can present as sepsis. Presentation: No date and time listed

Medical treatment of benign prostatic hyperplasia

Benign prostate hyperplasia (BPH) is a common disease, which affects male patients with incidence increasing with age. In recent years medical therapy for BPH has evolved, leading to postponement of surgical treatment. Alpha-blockers are considered first line treatment for patients with moderate to severe lower urinary tract symptoms (LUTS), while 5-alpha reductase inhibitors are prescribed in patients with moderate to severe LUTS and high risk of progression and acute urinary retention. Combination therapy is suitable for selected patients with LUTS and the choice of therapy depends on the main symptoms and risk of progression.

Timing of Intervention for Aortic Intramural Hematoma

Intramural hematoma (IMH) is one of the acute aortic syndromes along with acute aortic dissection and penetrating aortic ulcer. The three conditions can occur alone or in combination with overlapping presentation. Medical, open surgical, and endovascular treatment is tailored depending on clinical presentation, timing, and location within the aorta. Among patients who present with acute IMH affecting the ascending aorta (Type A), urgent open surgical repair is considered the primary line of treatment in patients who are suitable candidates and unstable. The management of IMH in the descending aorta and aortic arch (Type B) is similar to that applied to treat acute dissections in the same segment. Medical treatment with sequential imaging is recommended in patients with uncomplicated course, and endovascular repair is indicated in patients with rupture, persistent pain, end-organ ischemia, or rapid aortic enlargement. This review discusses the ideal timing for treatment of IMH.

A Systematic Review on the Safety and Efficacy of PCSK9 Inhibitors in Lowering Cardiovascular Risks in Patients With Chronic Kidney Disease.

Cardiovascular events caused by dyslipidemia are one of the leading causes of death in patients with Chronic Kidney Disease (CKD). Statins are the first line of treatment for patients with hyperlipidemia and in the treatment regimen for patients with CKD. Therefore, the introduction of Proprotein Convertase Subtilisin-Kexin type 9 inhibitors (PCSK9 inhibitors) is a viable and possibly effective treatment option for patients who, despite high doses of statins, struggle to lower their low-density lipoprotein cholesterol (LDL-C) levels. Our paper's objective is to explore the safety of these biological agents, particularly in patients with varying stages of impaired kidney function, and the correlating effectiveness in lowering their LDL-C levels, thereby reducing cardiovascular risks in these patients.We methodically retrieved relevant articles from PubMed, PubMed Central, Medline, and Google scholar in April 2022. We used the Medical Subject Heading (MeSH) Strategy and used the relevant keyword, then applied our inclusion and exclusion criteria; the initial search gave 10,542 results; with the removal of duplicates, irrelevant articles, and application of quality assessments done, we finally included 15 papers for our review with 37,188 patients.PCSK9 inhibitors are reliable, safe, and efficient therapy in lowering LDL-C levels in patients with CKD. However, its safety and efficacy in severe and end-stage kidney disease are grey, as other factors such as infections lead to morbidity and mortality. Future trials on chronic kidney disease and PCSK9 inhibitors should investigate the inhibitors' ability to improve kidney functions at all stages of kidney disease while lowering lipid levels and finally analyze the safety in patients with end-stage kidney disease.