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The proceedings contain 109 papers. The topics discussed include: dose intensity of palbociclib and initial body weight dosage: implications on progression free survival in 220 patients with ER+/HER2-negative metastatic breast cancer;characteristics of Nirmatrelvir/Ritonavir (Paxlovid) recipients and clinical interventions by oncology pharmacists at a tertiary outpatient cancer center;safe handling of non-carcinogenic drugs in the Ghent University Hospital: development, implementation and communication of hospital-specific guidelines;case series: use of olaparib in uncommon locations in patients with impaired homologous recombination;real-world data evaluation of medicines used in special situations in oncohematology: a retrospective study from a comprehensive cancer institution;Dostarlimab in the treatment of recurrent endometrial cancer: real life experience;medication-related osteonecrosis of the jaws and CDK4/6 inhibitors in breast cancer;and efficacy and safety outcomes of generic imatinib in adults with chronic myeloid leukemia (CML) following the switch from branded imatinib.
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Objectives: To evaluate how payers utilize Institute for Clinical and Economic Review (ICER) assessments to inform coverage or formulary decisions. Method(s): Double-blinded, web-based survey was fielded through Xcenda's research panel, the Managed Care Network, from June to July 2022. Result(s): A total of 51 payers from health plans (n=27), integrated delivery networks (n=12), and pharmacy benefit managers (n=12) participated in the survey. When assessing the usefulness of ICER's value assessment framework (VAF) to inform formulary decisions within their organizations, 57% of payers indicated it was extremely/very useful, 33% indicated somewhat useful, and 10% indicated not at all/not very useful. Most respondents (73%) agreed that ICER assessments are aligned with their organization's internal assessment. Utilization of ICER's VAF was most prevalent in high-cost drug or disease states (78%), rare/orphan disease states (71%), and oncology/hematology disease states (67%). Payers reported less use in primary care disease states (29%), COVID-19 (8%), and digital therapeutics (4%). In the last 24 months, 20% of payers reported ICER's recommendations often influenced coverage decisions, 59% indicated occasional influence, and 22% indicated no influence. In the last 24 months, payers indicated the top 5 ICER assessments that influenced their coverage decisions included high cholesterol (38%), Alzheimer's disease (36%), atopic dermatitis (33%), multiple myeloma (31%), and chemotherapy-induced neutropenia (28%). ICER assessments that were less impactful included beta thalassemia (3%), digital health technologies (3%), and supervised injection facilities (3%). Payers reported using ICER assessments to inform both expanded and restricted coverage decisions. Conclusion(s): Payers find ICER's VAF useful to inform their organization's formulary decisions. ICER's assessments often align with payers' internal assessments and are most frequently utilized for high-cost drugs or disease states. Payers indicate ICER assessments have affected both expansion and restriction in their coverage policies.Copyright © 2023
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In novel coronavirus disease 2019 (COVID-19), liver injury was found at a high rate, and reports from outside Japan revealed that such injury was related to severity. We examined the characteristics of liver injury in 15 cases of COVID-19. Thirteen of these patients received antiviral therapy, such as favipiravir, remdesivir, and hydroxychloroquine. Liver injury was observed in eight cases at admission for COVID-19. The hepatic CT attenuation values at admission were significantly lower in nine patients who developed liver damage or showed its exacerbation during the treatment than in the remaining patients. Drug-induced liver injury due to antiviral drug was suspected in six cases. Liver injury due to COVID-19 may be related to low hepatic CT attenuation values and be modified by antiviral drugs.Copyright © 2021 The Japan Society of Hepatology.
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Objectives: Cases of fulminant myocarditis after mRNA COVID-19 vaccination have been reported. The most severe may need venoarterial extracorporeal membrane oxygenation (V-A ECMO) support. Here we report two cases successfully rescued with V-A ECMO. Method(s): We included all the cases supported with V-A ECMO for refractory cardiogenic shock due to myocarditis secondary to a mRNA SARS-COV2 vaccine in the high-volume adult ECMO Program in Vall Hebron University Hospital since January 2020. Result(s): We identified two cases (table). One of them was admitted for out-of-hospital cardiac arrest. In both, a peripheral V-A ECMO was implanted in the cath lab. An intra-aortic balloon pump was needed in one case for left ventricle unloading. Support could be successfully withdrawn in a mean of five days. No major bleeding or thrombosis complications occurred. Definite microscopic diagnosis could be reached in one case (Image, 3). Treatment was the same, using 1000mg of methylprednisolone/day for 3 days. A cardiac magnetic resonance 10 days after admission showed a significant improvement in systolic function and diffuse oedema and subepicardial contrast intake in different segments (Image, 1-2). Both patients were discharged fully recovered. Conclusion(s): V-A ECMO should be established in cases of COVID-19 vaccine-associated myocarditis with refractory cardiogenic shock during the acute phase. (Table Presented).
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Background: Coronavirus disease-2019 (COVID-19) poses expectant mothers to a higher risk of serious complications and mortality. Following a risk-benefit review, a number of governmental and professional bodies from across the globe recently approved the COVID-19 vaccination during pregnancy. Aim(s): This study aimed to investigate knowledge, actual acceptance, and concerns about the COVID-19 vaccine among the obstetric population. Material(s) and Method(s): Participants were selected from among the expecting women who came for antenatal checkup during the study period (October 1, 2021-November 30, 2021). About 150 pregnant women who met the inclusion criteria and consented were recruited into the study. Data related to socio-demographic and clinical characteristics as well as knowledge, actual acceptance, and concerns about COVID-19 vaccine were collected through in-person interviews using a prestructured questionnaire. The SPSS version 23 was used to analyze data. The association between the attitude (acceptance and hesitance) of participants toward the COVID-19 vaccine and their sociodemographic and clinical profile was found by Fisher's exact test. Result(s): The actual acceptance of the COVID-19 vaccine among expecting women was 52.0%. The primary motive for accepting COVID-19 immunization was to protect the fetus, followed by the protection of one's own health. A significant association was found between COVID-19 vaccine acceptance and the level of education, socio-economic status, and presence of comorbidities. The leading causes for vaccine reluctance were concerns about the efficacy and safety of the vaccines and lack of awareness about their usage during pregnancy. Conclusion(s): Multifaceted activities are required to promote the effectiveness and safety profile of the COVID-19 vaccine as well as disseminate knowledge about its usage during pregnancy. Clinical significance: Unlike numerous other studies that have investigated the accepting attitude only, the present one has investigated the actual COVID-19 vaccine uptake among the obstetric population.Copyright © The Author(s).
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Objective: COVID-19 caused a deleterious impact on the health care system globally.The roll out of vaccines seems to be the only effective way to curtail the spread of disease.The purpose of this study is to assess the dermatological adverse effect of post COVID-19vaccination on a gender basis. Methodology: This was an observational,cross-sectional,questionnaire-based survey conducted in Pakistan.The sample comprises 518 participants. The questionnaire was self-designed. The trial lasted six months, from August 1, 2022, until January 31, 2023. We used a non-probability sampling technique.Dermatological adverse effects like burning pain, redness, rashes, and lymphadenopathy at the injection site were recorded.Fever was also noted. All the participants have received booster shots or double doses of any one of CCOVID-19 vaccines, such as AstraZeneca, Pfizer, Sinovac, Sinopharm,Pakvac, etc. A p-value of less than 0.05 was considered statistically significant.Qualitative data was reported as frequency and percentage, and quantitativedata was reported as standard deviation and mean. Result(s): The study included 518 subjects, of whom 262 were males and 256 were females. The mean age of male is 42.70+/-14.05 years and female is 39.04+/-14.6years with a significant difference observed between them (p=0.004). The most common complaint among dermatological adverse effects after first was pain. 106(40.5%) male and 132(51.6%) female reported painwith a significant difference observed between them (p=0.011) followed by swelling which was reported by 92(35.1%) males and 120(46.9%) females with a significant difference observed between them (p=0.006).Burning was reported in 92(35.1%) male and 148(57.8%) female with a significant difference observed between them(p<0.001). Fever was also quite commonly reported in both male 116(44.3%) and female 178(69.5%) with significantdifference observed between them (p<0.001),Likewise post 2nd dose of vaccination, pain was most commonly noted in 90(34.4%) male and female 124(48.4%) female with significant difference observed between them (p=0.001). Moreover, burning was reported by 80(30.5%) malesand 132(51.6%) females with a significant difference observed between them (p<0.001). rashes were reported by76(29.0%) males and 100(39.1%) females with a significant difference observed between them (p=0.016), lymphadenopathy was also significantly associated with genders, (p<0.001). Conclusion(s): This study concluded that the burning pain,redness,rashes,and lymphadenopathywere the most prevalent side effects in male and female post 1st and 2ndCOVID-19 vaccination.Furthermore fever was also reported in majority of subjects.In addition to this higher percentage of side effects were recorded in females as comparedto males.Copyright © 2023 Lahore Medical And Dental College. All rights reserved.
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This study compares the serological antibody level post-COVID-19 vaccine among healthy subjects and psychiatric patients on antidepressant therapy. It also examines the difference in antidepressants' side effects experienced by psychiatric patients following the completion of two vaccine doses. A comparative posttest quasi-experimental study was conducted among healthy subjects and psychiatric patients on antidepressant medication in a teaching hospital in Malaysia. Elecsys Anti-SARS-CoV-2 assay was used to detect the antibody titre between weeks 4 and 12 post vaccination. The antidepressant side-effect checklist (ASEC) was used to monitor the occurrence of antidepressant-related side effects pre-and post-vaccination. 24 psychiatric patients and 26 healthy subjects were included. There was no significant difference in the antibody level between the patients (median = 1509 u/ml) and the healthy subjects (median = 995 u/ml). There was no significant worsening in the antidepressant-related side effects. The antibody level post-COVID-19 vaccine did not differ significantly between patients on antidepressant therapy and healthy subjects. Additionally, there was no change in the antidepressant side effects experienced by the patients following the completion of the vaccine.Copyright © 2022, Research Trends (P) LTD.. All rights reserved.
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The use of machine learning and data-driven methods for predictive analysis of power systems offers the potential to accurately predict and manage the behavior of these systems by utilizing large volumes of data generated from various sources. These methods have gained significant attention in recent years due to their ability to handle large amounts of data and to make accurate predictions. The importance of these methods gained particular momentum with the recent transformation that the traditional power system underwent as they are morphing into the smart power grids of the future. The transition towards the smart grids that embed the high-renewables electricity systems is challenging, as the generation of electricity from renewable sources is intermittent and fluctuates with weather conditions. This transition is facilitated by the Internet of Energy (IoE) that refers to the integration of advanced digital technologies such as the Internet of Things (IoT), blockchain, and artificial intelligence (AI) into the electricity systems. It has been further enhanced by the digitalization caused by the COVID-19 pandemic that also affected the energy and power sector. Our review paper explores the prospects and challenges of using machine learning and data-driven methods in power systems and provides an overview of the ways in which the predictive analysis for constructing these systems can be applied in order to make them more efficient. The paper begins with the description of the power system and the role of the predictive analysis in power system operations. Next, the paper discusses the use of machine learning and data-driven methods for predictive analysis in power systems, including their benefits and limitations. In addition, the paper reviews the existing literature on this topic and highlights the various methods that have been used for predictive analysis of power systems. Furthermore, it identifies the challenges and opportunities associated with using these methods in power systems. The challenges of using these methods, such as data quality and availability, are also discussed. Finally, the review concludes with a discussion of recommendations for further research on the application of machine learning and data-driven methods for the predictive analysis in the future smart grid-driven power systems powered by the IoE.
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Objective: To assess the course of COVID-19 infections and the tolerability of the mRNA vaccines of Moderna and Pfizer/BioNTech and the viral vector vaccines from Astra Zeneca and Johnson & Johnson in adult patients with epilepsy (PWE). Method(s): From July 2020 to July 2021, we consecutively included adult outpatients with confirmed epilepsy. These PWE were interviewed about COVID-19 infections and vaccinations. Results of follow-up visits were added until the cut-off date (December 31, 2021). The data of COVID-19-infected without vaccinations or fully vaccinated PWE without COVID-19 infections were analyzed. Full vaccination was defined as a double vaccination with the Pfizer/BionTech, Moderna, or Astra Zeneca vaccines or a single Johnson & Johnson vaccination. Result(s): At cut-off, 612 of 1152 PWE fulfilled the inclusion criteria: 51 PWE had been infected without vaccination and 561 had full vaccination without infection. Among the infected PWE, 76.5% presented with symptoms;9.8% had a severe course (one death). The leading symptoms were influenza-like disorders (48.7% of infected PWE with symptoms), anosmia (28.2%), and ageusia (20.5%). Seizure increases or relapses after sustained seizure freedom occurred in 7.8%. Adverse events (AEs) were reported by 113 vaccinated PWE (20.1% of all vaccinated PWE). The leading AEs were fatigue, fever, and headache. The AE rate per vaccine was 14.0% for Pfizer/BionTech, 32.7% for Moderna, 25.8% for Astra Zeneca, and 46.2% for Johnson & Johnson. Of the AEs, 93.3% lasted <=1 week. Seizure increase or relapse occurred in 1.4% and was significantly less frequent than in the infected group (p= 0.0016). Conclusion(s): The course of COVID-19 infections and the tolerability of the vaccines were similar as in the general population, yet, seizure worsening occurred more often after the infection than after the vaccination.Copyright © 2023, The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, part of Springer Nature.
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Introduction: Macrophage activation syndrome (MAS) is a severe hyper inflammatory condition caused by the over-activation and proliferation of T cells, NK cells and macrophages. It is often associated with complications of rheumatic/immune diseases. We present a case of a 15-year-old female who experiences recurrent episodes of MAS without any known definitive underlying etiology. Case Presentation: A 15-year-old previously healthy female developed fatigue, fevers, myalgia, chest pain, splenomegaly and lymphadenopathy 10 days after receiving her first Pfizer COVID-19 vaccine. Her symptoms recurred 10 days after receiving the second dose. Her myocarditis, MIS-C, and infectious work up was negative except for positive EBV IgG. Laboratory studies revealed anemia, hypertriglyceridemia, hypofibrinogenemia, and hyperferritinemia. She initially responded to decadron;however, her symptoms recurred with steroid taper. Bone marrow biopsy revealed hemophagocytosis. Whole exome sequencing (WES) revealed a heterozygous variant of uncertain significance in UNC13D c.962C>A (p.Thr321Asn). She had multiple re-admissions with significantly elevated inflammatory markers, including extremely high IL2-R, IL-18 and CXCL9. Each episode was complicated by an acute viral infection. She responds to high dose steroids, anti-IL-1, and JAK inhibitors. Nonetheless, it has been difficult to wean decadron without triggering a flare. She continues to require increasing doses of baricitinib. Discussion(s): MAS may be seen as a complication of rheumatic diseases, as well as inborn errors of immunity. However, none of these conditions have been diagnosed in this patient despite extensive testing, including WES. The degree of her immune dysregulation has been very severe making her disease process unpredictable and extremely difficult to control. She has frequent flares precipitated by viral infections or attempts at adjusting her immunomodulators. Weaning her medications has been challenging as she continues to require increasing doses of baricitinib and corticosteroids. The UNC13D gene is associated with autosomal recessive familial hemophagocytic lymphohistiocytosis type 3 (FHL3). Our patient is heterozygous for an UNC13D variant of uncertain significance. Additional genetic inquiries with whole genome sequencing to help elucidate the underlying etiology of her severe condition is being conducted. We hypothesize she developed MAS due to a combination of genetic predisposition, prior EBV infection, and immune stress associated with the COVID-19 vaccine. [Formula presented] [Formula presented] [Formula presented]Copyright © 2023 Elsevier Inc.
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The patient presented with nausea, appetite loss, and fatigue. She had received two doses of Pfizer/BioN-Tech BNT162b2 mRNA vaccine (COMIRNATY) for coronavirus disease 2019 (COVID-19). Acute liver injury was noted 14 days after the first dose of the vaccine. Re-exposure through the second dose worsened the liver injury. After liver biopsy on the third day of admission, methylprednisolone (1000 mg) was administered. Liver histology showed acute hepatitis with diffuse lobular inflammation/necrosis and lymphocyte-dominant infiltra-tion in the portal areas. The patient was diagnosed with drug-induced liver injury due to the COVID-19 vaccine based on the Digestive Disease Week Japan 2004 (DDW-J) scale, which assesses the temporal relationship, liver biopsy, and laboratory findings. With improvements in the blood test parameters, prednisolone was gradually tapered and stopped. One month later, no biochemical signs of relapse were noted. To our knowledge, this is the first report describing liver injury after the administration of the Pfizer COVID-19 vaccine in Japan.Copyright © 2022 The Japan Society of Hepatology.
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BACKGROUND: Vaccines are one of the best interventions developed for eradicating COVID-19. In Albania, COVID-19 vaccination uses different types of vaccines: Pfizer, AstraZeneca, CoronaVac, and Sputnik V. Like any other vaccine, these have side effects too. AIM: This study was carried out to identify the perception of the side effects of vaccines. METHOD(S): A quantitative study using a cross-sectional survey was conducted between April and September 2021 to collect data on the effects of the COVID-19 vaccine among individuals in Shkodra region. Data were collected online through a self-administered survey created on Google Forms which had been randomly delivered to individuals (aged >=18 years) using social media sites (Email and WhatsApp). All data collected were analyzed with Microsoft Office Excel 2010, using the exact Fisher's test and x2 test. RESULT(S): This study included 292 citizens, out of which 200 were female and 92 were male;62% were from urban areas and 38% from rural areas of Shkodra region. The random sample of the citizens who took part in this study is 44.5% (18-30 years old). A massive percentage of the participants, 66.4%, had received the second dose of the vaccine. Our study shows that 55.8% of these citizens have had side effects after the first vaccination dose, and only 43.8% have had side effects after the second dose. About 80.6% of the participants were well informed about the type of vaccine they got. CONCLUSION(S): Side effects from vaccines were reported. Injection site pain and fatigue were the most common first dose side effects (55.8%). The same side effects were reported for the second dose. The side effects were presented during the first 12 h after the vaccination in most cases. Side effects were more prevalent in people >50 years old. Older people have a higher probability to have more side effects from the COVID vaccine. There is no statistically significant relationship between gender and the presence of the side effect from the COVID vaccine. People living in urban areas have a higher probability to have side effect from COVID vaccine comparing with people living in rural areas. People being vaccinated with Pfizer vaccine have a higher probability to admit the presence of side effects.Copyright: © 2022 Zamira Shabani, Arketa Guli, Julian Kraja, Arlinda Ramaj, Nertila Podgorica.
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Introduction: Combination of daratumumab (Dara) and lenalidomide (Len) may enhance the function of teclistamab (Tec), potentially resulting in improved antimyeloma activity in a broader population. We present initial safety and efficacy data of Tec-Dara- Len combination in patients with multiple myeloma (MM) in a phase 1b study (MajesTEC-2;NCT04722146). Method(s): Eligible patients who received 1-3 prior lines of therapy (LOT), including a proteasome inhibitor and immune-modulatory drug, were given weekly doses of Tec (0.72-or- 1.5 mg/kg with step-up dosing) + Dara 1800 mg + Len 25 mg. Responses per International Myeloma Working Group criteria, adverse events (Aes) per CTCAE v5.0, and for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) per ASTCT guidelines, were assessed. Result(s): 32 patients received Tec-Dara- Len (0.72 mg/kg, n = 13;1.5 mg/kg, n = 19). At data cut-off (11 July 2022), median follow-up (range) was 5.78 months (1.0-10.4) and median treatment duration was 4.98 months (0.10-10.35). Median age was 62 years (38-75);87.5% were male. Median prior LOT was 2 (1-3), 18.8% were refractory to Dara and 28.1% refractory to Len. CRS was most frequent AE (81.3% [n = 26], all grade 1/2), 95% occurred during cycle1. Median time to onset was 2 days (1-8), median duration was 2 days (1-22). No ICANS were reported. Frequent Aes (>=25.0% across both dose levels) were neutropenia (75.0% [n = 24];grade 3/4: 68.8% [n = 22]), fatigue (43.8% [n = 14];grade 3/4: 6.3% [n = 2]), diarrhoea (37.5% [n = 12];all grade 1/2), insomnia (31.3% [n = 10];grade 3/4: 3.1% [n = 1]), cough (28.1% [n = 9];all grade 1/2), hypophosphatemia (25.0% [n = 8];all grade 1/2), and pyrexia (25% [n = 8];grade 3/4: 6.3% [n = 2]). Febrile neutropenia frequency was 12.5% (n = 4). Infections occurred in 24 patients (75.0%;grade 3/4: 28.1% [n = 9]). Most common were upper respiratory infection (21.9% [n = 7]), COVID-19 (21.9% [n = 7]), and pneumonia (21.9% [n = 7]). Three (9.4%) had COVID-19 pneumonia. One (3.1%) discontinued due to COVID-19 infection and this patient subsequently died of this infection. Overall response rate (ORR, median follow-up) was 13/13 (8.61 months) at 0.72 mg/kg and 13/16 evaluable patients (less mature at 4.17 months) at 1.5 mg/kg. 12 patients attained very good/better partial response at 0.72 mg/kg dose, and response was not mature for 1.5 mg/kg group. Median time to first response was 1.0 month (0.7-2.0). Preliminary pharmacokinetic concentrations of Tec-Dara- Len were similar as seen with Tec monotherapy. Tec-Dara- Len- treatment led to proinflammatory cytokine production and T-cell activation. Conclusion(s): The combination of Tec-Dara- Len has no new safety signals beyond those seen with Tec or Dara-Len individually. Promising ORR supports the potential for this combination to have enhanced early disease control through the addition of Tec. These data warrant further investigation.
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Bruton tyrosine kinase inhibitors (BTKis) were approved for use at the end of 2013 and have since been used for indications including chronic lymphocytic leukaemia (CLL), Waldenstrom's macroglobulinaemia and mantle cell lymphoma. The use of BTKis has increased significantly in the UK since they achieved NICE (National Institute for Health and Care Excellence) approval for frontline treatment of CLL in 2021. However, they are associated with significant adverse cardiovascular events. In September 2021 the British Journal of Haematology published good practice guidelines for the management of cardiovascular complications of BTKis. Our aim was to see whether these guidelines had been adhered to for patients taking BTKis. Method(s): Data was collected for all patients being prescribed BTKis (ibrutinib and acalabrutinib) in the South Tees NHS Trust in July 2022. Patients' medical records were used to assess whether their management adhered to the good practice guidelines. Data was collated for 67 patients in total. Result(s): The data showed that although all patients were consented for the risk of atrial fibrillation only 6% were consented for hypertension and only 1.5% for ventricular arrhythmias and sudden cardiac death. The guidelines recommend a baseline ECG (electrocardiogram) on commencement of treatment;however, only 7% had this completed and 0% had the minimum monitoring recommendation of 6-monthly ECGs. Thirty patients (45%) had an indication for a baseline echocardiogram;however, only one had this completed. For patients reporting symptoms of syncope, dizziness or palpitations only 50% had an ECG completed. Three patients developed worsening heart failure. The recommendations suggest referral to a cardio-oncologist;however, due to lack of availability of this service the referrals were instead made to the usual cardiologist. Conclusion(s): Although there was a lack of compliance with guideline recommendations, it should be considered that most usual checks were affected by COVID-19 outbreaks and a drop in face-to- face clinics, which were replaced by phone clinics and home delivery of medications. However, the premade consent forms for BTKis need to be updated to include consent for ventricular arrhythmias and sudden cardiac death. There also needs to be routine procedures in place to ensure that regular blood pressure testing and ECG monitoring occurs and that there is prompt recognition of cardiovascular complications. Action and implementation: To ensure improved compliance with these guidelines we plan to update our consent forms and create a proforma for clinic use to ensure that clinicians are aware of the various monitoring criteria required.
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The TG6002.03 trial is a dose-escalation phase 1 clinical trial of TG6002 infusion via the hepatic artery in patients with liver-dominant colorectal cancer metastases. TG6002 is an engineered Copenhagen strain oncolytic Vaccinia virus, deleted of thymidine kinase and ribonucleotide reductase to enhance tumor selective viral replication and expressing FCU1, an enzyme converting the non-cytotoxic prodrug 5-fluorocytosine (5-FC) into the chemotherapeutic compound 5-fluorouracil (5-FU). In this trial, patients with advanced unresectable liver-dominant metastatic colorectal cancer who had failed previous oxaliplatin and irinotecan-based chemotherapy were treated with up to 2 cycles of TG6002 infusion 6 weeks apart via the hepatic artery on day 1 combined with oral 5-FC on days 5 to 14 (where day 1 = TG6002 infusion). TG6002 infusion was performed over 30 minutes via selective catheterization of the hepatic artery proper. 5-FC oral dosing was 50mg/kg x4 daily. Blood was sampled for TG6002 pharmacokinetics and 5-FC and 5-FU measurements. Sampling of liver metastases was performed at screening and on day 4 or day 8 for virus detection and 5-FC and 5-FU quantification. In total, 15 patients (median age 61 years, range 37-78) were treated in 1 UK centre and 2 centres in France and received a dose of TG6002 of 1 x 106 (n=3), 1 x 107 (n=3), 1 x 108 (n=3), or 1 x 109 pfu (n=6). Fourteen of the 15 patients received a single cycle of treatment, including one patient who did not received 5-FC, and one patient received two cycles. TG6002 was transiently detected in plasma following administration, suggesting a strong tissue selectivity for viral replication. In the highest dose cohort, a virus rebound was observed on day 8, concordant with replication time of the virus. In serum samples, 5-FU was present on day 8 in all patients with a high variability ranging from 0.8 to 1072 ng/mL and was measurable over several days after initiation of therapy. Seven of the 9 patients evaluable showed the biodistribution of the virus in liver lesions by PCR testing on day 4 or day 8. Translational blood samples showed evidence for T-cell activation and immune checkpoint receptor-ligand expression. At 1 x 109 pfu, there was evidence for T-cell proliferation and activation against tumour-associated antigens by ELISpot and for immunogenic cell death. In terms of safety, a total of 34 TG6002-related adverse events were reported, of which 32 were grade 1-2 and 2 were grade 3. The maximum tolerated dose was not reached, and a single dose-limiting toxicity was observed consisting of a myocardial infarction in a context of recent Covid-19 infection in a 78-year-old patient. These results indicate that TG6002 infused via the hepatic artery in combination with oral 5-FC was well tolerated, effectively localized and replicated in the tumor tissues, expressed its therapeutic payload and showed anti-tumoral immunological activity.
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Introduction: Abdominal wall surgery has been one of the major victims of the COVID-19 pandemic, with a large number of patients who have seen their surgery delayed and many are still waiting to be operated on today. On the other hand, botulinum toxin is one of the main protagonists in optimizing abdominal wall surgery, especially important in complex hernia, but we must not forget that it can have adverse effects. Case report: We present the case of a 54-year-old man with a history of obesity, diabetes, hypertension, chronic renal failure and kidney transplant in 2000, who presented a midline incisional hernia as a result of an epigastric hernia operated on in 2006 and subsequently two onlay permanent synthetic mesh in 2010 and 2015. In February 2020 he presented an incisional hernia M2-4W3R3 with a volume of 35%, botox was infiltrated as optimization for surgery and while awaiting placement of a pneumoperitoneum catheter, the surgery was suspended due to the COVID-19 situation. He returns to our clinics in 2022 with a growth of the hernia and a volume of 95%. Weight loss, botulinum toxin and preoperative pneumoperitoneum were indicated. We performed a reconstruction of the abdominal wall with bilateral transversus abdominal release and preperitoneal 45x60cm polyvinylidene fluoride mesh and abdominoplasty. Discussion(s): Botulinum toxin can facilitate abdominal surgery, especially in complex hernias, but we must not forget that blocking the abdominal muscles can have adverse effects. The COVID-19 pandemic has been especially hard on surgical waiting lists, delaying surgeries and aggravating pathologies.
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BackgroundThe Covid19 pandemic started in late 2019 and went through different phases by spreading from China around the whole globe. During the pandemic different mutation types got predominant from original Wuhan type through Alpha, Delta and Omicron variate BA 1/2 to BA 4/5 with different infectiousity and different potential to harm people´s health status. Immunization/ vaccination program started late 2020, first booster phase started midst of 2021, second booster phase in late 2021/ beginning of 2022 and Omicron specific booster phase midst of 2022.ObjectivesIs there a need of further iatrogenic (booster) immunization/ vaccination after 2 years of immunization/ vaccination program from efficacy driven analysis and safety issues standpoint?MethodsAnalysis of Covid-19 antibody development every three months since August 2021 with comparison of infection rates and assessment of safety parameters by assessing D-Dimers as potential endothelium damage marker in 725 patients (600 female, 125 male, age mean: 62,2 years) of a German rheumatological practice to improve the medical care.ResultsIn 99 % of the patients longstanding immune memory could be shown by analyzing the antibody curves in different exemplary shown biologic and iatrogenic immunization pathways after 2 years of immunization/ vaccination program and biologic immunization, mainly by Delta variate since late 2021 and Omicron variate since beginning of 2022. In 38.5 % of the patients the safety concerns of potential endothelium damage by analysing D-Dimers every 3 months showed a side effect potential of at least 8 months after every MRNA/ Vector immunization, but not after protein based vaccination and even not after infections in that amount.ConclusionOut of the obligation "nil nocere” no further iatrogenic Covid-19 immunization/ vaccination is of need in nearly all (99 %) already immunized people. At present only adult people with very low antibody levels (at least below 64 BAU/ml) (considering the infection or iatrogenic immunization/ vaccination status and time since last spike protein contact) and not yet immunized adult people should be forseen for iatrogenic immunization/ vaccination with protein based or attenuated viral vaccines or in rare cases one Omicron specific MRNA immunization drug. In that case D-Dimer controls for up to 8 months should be obligatory to detect endothelial damage side effect of MRNA (or Vector) technique. Intense cardiovascular monitoring (small vessels) of MRNA/ Vector immunized people in the next 10 – 20 years is necessary.Figure 1.References[1] Pohl C;SAFETY AND EFFICACY ASSESSMENT OF COVID-19 IMMUNIZATIONS/ VACCINATIONS IN PATIENTS OF A GERMAN GENERAL RHEUMATOLOGICAL PRACTICE;EULAR 2022 Poster POS1213;https://doi.org/10.1136/annrheumdis-2022-eular.1389[2] McConeghy KW et al. Effectiveness of a Second COVID-19 Vaccine Booster Dose Against Infection, Hospitalization, or Death Among Nursing Home Residents - 19 States, March 29-July 25, 2022. MMWR Morb Mortal Wkly Rep. 2022 Sep 30;71(39):1235-1238. doi: 10.15585/mmwr.mm7139a2. PMID: 36173757;PMCID: PMC9533729.[3] Bowe, B. Et al. Acute and postacute sequelae associated with SARS-CoV-2 reinfection. Nat Med 28, 2398–2405 (2022). https://doi.org/10.1038/s41591-022-02051-3[4] Hui-Lee Wong et al. Surveillance of COVID-19 vaccine safety among elderly persons aged 65 years and older, Vaccine, Volume 41, Issue 2, 2023, Pages 532-539, ISSN 0264-410X, https://doi.org/10.1016/j.vaccine.2022.11.069.[5] Maher AK et al. Transcriptional reprogramming from innate immune functions to a pro-thrombotic signature by monocytes in COVID-19. Nat Commun. 2022 Dec 26;13(1):7947. doi: 10.1038/s41467-022-35638-y. PMID: 36572683;PMCID: PMC9791976.[6] Erich Freisleben;Sie wollten alles richtig machen – Dokumentation eines verschwiegenen Leidens – Bericht eines Hausarztes über die Nebenwirkungen der Corona Impfungen;Nov 11, 2022;Cajus Verlag[7] Positive Testrate Germany – https://www.rki.de/DE/Content/InfAZ/N/Neuartiges_Coronavirus/Testzahl.htmlAcknowledgementsThanks to my fami y, all my patients and my collegues for supporting me in my research to improve my personal patient care.Disclosure of InterestsNone Declared.
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Timely, effective, and safe antiviral therapy in COVID-19 patients reduces complications, disability and mortality rates. The greatest concern with remdesivir is the risk of drug-induced liver injury, including in patients whose liver function is compromised by COVID-19. The aim of the study was to investigate the efficacy and safety of remdesivir in patients with confirmed SARSCoV-2 infection who had been admitted to an infectious diseases hospital in the Volgograd region in March 2022. Material(s) and Method(s): the authors carried out an open, non-randomised, single-arm study using medical records of 234 patients who had been diagnosed with "U07.1 COVID-19, virus identified" and prescribed remdesivir upon admission. The effectiveness of therapy was evaluated using two criteria: the need for oxygen supplementation or ventilatory support, or mortality. The authors conducted the evaluation on days 7, 14, and 28 using the six-point ordinal severity scale by Y. Wang et al. The safety of therapy was assessed on the basis of complaints and changes in laboratory findings. Result(s): for the patients prescribed remdesivir at admission, the 7-day mortality rate was 3.0%, the 14-day mortality rate was 5.6%, and the 28-day mortality rate was 7.3%. With the exception of a patient with myocardial infarction, all the patients who had been hospitalised with mild COVID-19 and prescribed remdesivir did not require oxygen therapy and/or transfer to intensive care and were discharged following recovery. The patients with moderate to severe COVID-19 had the 14-day mortality rate of 6.4% and the 28-day mortality rate of 8.6%. 17 patients (7.2%) discontinued remdesivir prematurely for various reasons, including adverse drug reactions. Remdesivir therapy of 5-10 days was associated with an increase in ALT activity by 2.7 +/- 0.8 times in 15.9% of patients with mild COVID-19, by 3.8 +/- 1.8 times in 20.4% of patients with moderately severe COVID-19, and by 4.8 +/- 2.7 times in 24% (12/50) of patients with severe COVID-19. In two patients (0.9%), the increase exceeded 10-fold the upper limit of normal. Conclusion(s): the obtained results support recommending remdesivir to patients with mild, moderate and severe COVID-19, including those with moderately elevated baseline activity of hepatic transaminases.Copyright © NEICON ISP LLC. All rights reserved.
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Introduction: Croatian National Cancer Registry of Croatian Institute for Public Health reported that in year 2020 lung cancer was the second most common cancer site diagnosed in men with 16% and the third most common in women with 10% incidence among all cancer sites. Unfortunatelly lung cancer has the highest mortality in both men and women. Haematological malignancies had 7% share in all malignancies in both male and female cances cases. In 2020 190 newly diagnosed cases of lymphatic leukemia in men and 128 cases in women were reporeted, meaning 1.5 and 1.2% of all malignancies, respectively. Chronic lymphatic leukemia (CLL) is an advanced age disease and incidence increases with age. Impaired immunity, T and B cell dysfunction in CLL, chromosomal aberations, long-term immunosuppressive therapy and genetic factors can all cause secondary malignancies. Co- occurence of solid tumors and CLL is very rare. Although patiens with CLL have an increased risk of developing second primary malignancies including lung carcinoma, the data about their clinical outcomes are lacking. Parekh et al. retrospectively analyzed patients with simultaneous CLL and lung carcinoma over a 20-year period, and they found that ~2% of patients with CLL actually developed lung carcinoma. The authors claimed that up to 38% of patients will also develop a third neoplasm more likely of the skin (melanoma and basal cell carcinoma), larynx (laryngeal carcinoma) or colon. Currently there are no specific guidelines for concurrent CLL and non-small cell lung carcinoma (NSCLC) treatment. Usually, when the tumors are diagnosed simultaneously, treatment is based to target the most aggressive malignancy, as the clinical outcomes depend on the response of the tumor with the poorest prognosis. For this reason, a multidisciplinary approach is mandatory. Case report: A patient with history of coronary heart disease, myocardial infarction and paroxysmal atrial fibrillation was diagnosed in 2019 (at the age of 71) with B chronic lymphocytic leukemia with bulky tumor (inguinal lymph nodes 8x5 cm), stage B according to Binet, intermediate risk. He was treated with 6 cycles of chemoimmunotherapy (rituximab/cyclofosfamid/fludarabine). In 10/2019 remission was confirmed, but MSCT described tumor in the posterior segment of upper right lung lobe measuring 20x17 mm and bilateral metastases up to 11 mm. Bronchoscopy and biopsy were performed, and EGFR neg, ALK neg, ROS 1 neg, PD-L1>50% adenocarcinoma was confirmed. He was referred to Clinical Hospital Center Osijek where monotherapy with pembrolizumab in a standard dose of 200 mg intravenously was started in 01/2020. Partial remission was confirmed in October 2020. Immunotherapy was discontinued due to development of pneumonitis, dysphagia and severe weight loss (20kg), but without radiologically confirmed disease progression. At that time he was referred to our hospital for further treatment. Gastroscopy has shown erosive gastritis with active duodenal ulcus, Forrest III. Supportive therapy and proton pump inhibitor were introduced. After complete regression of pneumonitis, improvement of general condition and resolution of dysphagia, no signs of lung cancer progression were found and pembrolizumab was reintroduced in 12/2021. Hypothyroidism was diagnosed in 01/2021 and levothyroxine replacement ther apy was started. In 03/2021 he underwent surgical removal of basal cell carcinoma of skin on the right temporal region with lobe reconstruction. From 02/2021, when pembrolizumab was reintroduced, regression in tumor size was continously confirmed with complete recovery of general condition. He was hospitalized for COVID 19 infection in 09/2021, and due to complications pembrolizumab was discontinued till 11/2021. Lung cancer immunotherapy proceeded till 11/2022, when Multidisciplinary team decided to finish pembrolizumab because of CLL relapse. CLL was in remission till August 2022 when due to B symptoms, lymphcytosis, anemia and generalized lymphadenopathy, hematological workup including biopsy of cervical lymph node was performed and CLL/SLL relapse was confirmed. Initially chlorambucil was introduced, but disease was refractory. Based on cytogenetic test results (IGHV unmutated, negative TP53) and due to cardiovascular comorbidity (contraindication for BTK inhibitors) venetoclax and rituximab were started in 01/2023. After just 1 cycle of treatment normal blood count as well as regression of B symptoms and peripheral lymphadenopathy occured, indicating the probability of complete disease remission. In our patient with metastatic lung adenocarcinoma excellent disease control is achieved during 41 month of treatment in first line setting. Furthermore, relapsed/refractory CLL/SLL is currently in confirmed remission. Conclusion(s): Successful treatment of patients with multiple primary malignancies is based on multidisciplinarity, early recognition and management of side effects, treatment of comorbidities with the aim of prolonging life, controlling symptoms of disease and preserving quality of life.