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Amantadine has begun to be used as a possible alternative in COVID-19 therapy to mitigate its effects. There is anecdotal evidence that patients with Parkinson's disease (PD) treated with amantadine and who test positive for COVID-19 often do not develop clinical manifestations of COVID-19. Objective(s): to compare the clinical course of COVID-19 in patients with PD who took or did not take amantadine sulfate. Patients and methods. A prospective continuous study included 142 patients with PD who were treated in Republican Clinical Diagnostic Center for Extrapyramidal Pathology and Botulinum Therapy in Kazan from October 2021 to January 2022. Patients filled out a proprietary internally developed questionnaire. Results and discussion. Out of 142 individuals with PD COVID-19 occurred in 77 (54.2%), of which 52.0% had a mild course, 39.0% had a moderate course, 2.6% had a severe course, and in 6.5% the severity of the disease has not been established. Deterioration after COVID-19 infection was noted by 36% of patients: the appearance or increase in motor fluctuations (41%), increased tremor, stiffness or slowness (31%), the appearance of "exhaustion" of the effect of a single dose of levodopa (13%), the appearance or increased dyskinesia (21%), hallucinations (3.5%). Patients taking amantadine sulfate had PD much longer (11.5+/-5.62 years versus 5.12+/-3.24 years) and had a more pronounced (III-IV) stage of the disease. These patients were more likely to experience mild COVID-19 (in 60.87% of cases), in contrast to patients not receiving amantadine sulfate (only in 48.15% of cases). There was no correlation between the severity of COVID-19 and levodopa intake. Conclusion. The results of the study showed that patients with PD taking amantadine sulfate are more likely to have a mild course of COVID-19.Copyright © 2022 Ima-Press Publishing House. All rights reserved.
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INTRODUCTION. The aetiology of Kawasaki disease (KD) remains unknown. Changes in infectious exposure during the COVID-19 pandemic owing to infection prevention measures may have affected the incidence of KD, supporting the pathogenic role of an infectious trigger. The purpose of this study was to evaluate the incidence, phenotype and outcome of KD before and during the COVID-19 pandemic in Denmark. METHODS. This was a retrospective cohort study based on patients diagnosed with KD at a Danish paediatric tertiary referral centre from 1 January 2008 to 1 September 2021. RESULTS. A total of 74 patients met the KD criteria of whom ten were observed during the COVID-19 pandemic in Denmark. Alof these patients were negative for SARS-CoV-2 DNA and antibodies. A high KD incidence was observed during the first six months of the pandemic, but no patients were diagnosed during the following 12 months. Clinical KD criteria were equally met in both groups. The fraction of intravenous immunoglobulin (IVIG) non-responders was higher in the pandemic group (60%) than in the in the pre-pandemic group (28.3%), although the rate of timely administered IVIG treatment was the same in both groups (>= 80%). Coronary artery dilation was observed in 21.9% in the pre-pandemic group compared with 0% in KD patients diagnosed during the pandemic. CONCLUSION. Changes in KD incidence and phenotype were seen during the COVID-19 pandemic. Patients diagnosed with KD during the pandemic had complete KD, higher liver transaminases and significant IVIG resistance but no coronary artery involvement.Copyright © 2023, Almindelige Danske Laegeforening. All rights reserved.
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Introduction: Automatic drug dispensers are now widely used in critical care.1-2 They can provide information about dispensed drugs. Good practice in sedation restricts the use of sedatives and titrates doses to defined responses.3-4 Objectives: To extract drug dispenser issuing records for sedatives and link these to patient records to evaluate sedative use. Method(s): in October 2019, we introduced two Omnicell XT automated dispensing cabinets (Omnicell inc. CA, USA) into a 42 bedded general/neurological unit. ICNARC (Intensive care national audit and research centre) and CCMDS (Critical care minimum data set) data was collected using the Ward Watcher program. Dispenser issuing records for alfentanil, propofol and midazolam were obtained as Excel files for 13 months from January 2020. Output time stamps were converted to dates and times. Outputs were linked to outputs of the ICNARC and CCMDS records for the patients that the drugs were issued to. All the outputs had patients identified by their unique hospital numbers. These were used in Excel "power queries" to produce a spread sheet with a single row per patient. Multiple admissions used the first diagnosis, the final outcome and the total length of stay. The total dose of sedatives was calculated from ampoule dose and number. The duration of treatment was calculated from the first and last issues of the drug. ICNARC codes were used to identify the primary system in the admission diagnostic code and those patients admitted for COVID-19. Variables were compared using Chi Squared, Mann-Whitney U and Kruskal Wallis Tests. The significance of associations was established using Spearman's Rho. Linear regression was used to define relationships more clearly. Result(s): Table one summarises the patient characteristics with respect to all admissions during the study period and for patients who had had the studied drugs issued to them. Midazolam was used in fewer patients, they were more likely to be male, heavier (p>0001) and to die than patients receiving Propofol or Alfentanil (p>0.001). With respect to diagnostic groups, all the sedatives, particularly Midazolam (p<0.001), were more likely to be used in patients with COVID-19. The relationship between the dose of sedative drugs and patient age and weight was explored using the dose per advanced respiratory day. All three drugs had a significant but weak negative relationship with age, lower doses being given to older people (Propofol r2 = 0.02, p=0.01. Alfentanil r2 = 0.04, p=0.00. Midazolam r2 = 0.07, p=0.00.). There was also a weak but significant relationship between increasing dose of Propofol with patient weight (r2 = 0.02, p=0.01), but there was no relation between weight and doses of the other drugs. Conclusion(s): Information from automatic drug dispensers can be interpreted and combined with other datasets to produce clinically relevant information. The limited weak relationships between drug dose and age and weight suggests that sedative drugs could have been better titrated to response.
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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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Lung cancer is the leading cause of cancer related deaths worldwide, with a relatively low 5-year survival rate. Although there are some therapies against lung cancer, new effective treatment options are urgently required. Recently during the COVID-19 pandemic, we have seen that SARSCoV-2 binds to its receptor angiotensin-converting enzyme 2 (ACE2) via spike S1 to enter the cells. This study underlines the importance of SARS-CoV-2 spike S1 in inducing death in human lung cancer cells. Interestingly, we have seen that recombinant spike S1 treatment at very low doses led to death of human A549 lung cancer cells. On the other hand, boiled recombinant SARS-CoV-2 spike S1 remained unable to induce death, suggesting that the induction of cell death in A549 cells was due to native SARS-CoV-2 spike S1 protein. SARS-CoV-2 spike S1-induced A549 cell death was also inhibited by neutralizing antibodies against spike S1 and ACE2. Moreover, our newly designed wild type ACE2-interacting domain of SARS-CoV-2 (wtAIDS), but not mAIDS, peptide also attenuated SARS-CoV-2 spike S1-induced cell death, suggesting that SARS-CoV-2 spike S1- induced death in lung cancer cells depends on its interaction with ACE2 receptor. Similarly, recombinant spike S1 treatment also led to death of H1299 and H358 human lung cancer cells. Finally, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) intoxication led to the formation tumors in lungs of A/J mice and alternate day intranasal treatment with low dose of recombinant SARS-CoV-2 spike S1 from 22-weeks of NNK insult (late stage) led to induced apoptosis and tumor regression in the lungs. These studies indicate that recombinant SARS-CoV-2 Spike S1 protein may have implications in the treatment of lung cancer.
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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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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: Lung cancer is the leading cause of cancer-related death in the US with an estimated 236,740 new cases and 130,180 deaths expected in 2022. While early detection with low-dose computed tomography reduces lung cancer mortality by at least 20%, there has been a low uptake of lung cancer screening (LCS) use in the US. The COVID-19 pandemic caused significant disruption in cancer screening. Yet, little is known about how COVID-19 impacted already low use of LCS. This study aims to estimate LCS use before (2019) and during (2020 and 2021) the COVID-19 pandemic among LCS-eligible population in the US. Method(s): We used population-based, nationally representative, cross-section data from the 2019 (n=4,484), 2020 (n=1,239) and 2021 (n=1,673) Behavioral Risk Factor Surveillance System, Lung Cancer Screening module. The outcome was self-reported LCS use among eligible adults in the past 12 months. For 2019 and 2020, the eligibility was defined based on US Preventive Services Task Force (USPSTF) initial criteria-adults aged 55 to 80 years old, who were current and former smokers (had quit within the past 15 years) with at least 30 pack years of smoking history. For 2021, we used the USPSTF updated criteria- adults aged 50 to 80 years, current and former smokers (who had quit within the past 15 years) with at least 20 pack years of smoking history. We applied sampling weights to account for the complex survey design to generate population estimates and conducted weighted descriptive statistics and logistic regression models. Result(s): Overall, there were an estimated 1,559,137 LCS-eligible respondents from 16 US states in 2019 (AZ, ID, KY, ME, MN, MS, MT, NC, ND, PA, RI, SC, UT, VT, WV, WI), 200,301 LCS-eligible respondents from five states in 2020 (DE, ME, NJ, ND, SD), and 668,359 LCS-eligible respondents from four states in 2021 (ME, MI, NJ, RI). Among 2,427,797 LCS-eligible adults, 254,890;38,875;and 122,240 individuals reported receiving LCS in 2019, 2020 and 2021, respectively. Overall, 16.4% (95% CI 14.4-18.5), 19.4% (95% CI 15.3-24.3), and 18.3% (95% CI 15.6-21.3) received LCS during 2019, 2020, and 2021, respectively. In all years, the proportion of LCS use was higher among adults aged 65-74, insured, those with fair and poor health, lung disease and history of cancer (other than lung cancer). In 2020, a higher proportion of adults living in urban areas reported receiving LCS compared to those living in rural areas (20.36% vs. 12.7%, p=0.01). Compared to non-Hispanic White adults, the odds of receiving LCS was lower among Hispanic adults and higher among Non-Hispanic American Indian/Alaskan Native adults in 2020 and 2021, respectively. Conclusion(s): LCS uptake remains low in the US. An estimated 2,011,792 adults at high-risk for developing lung cancer did not receive LCS during 2019, 2020 and 2021. Efforts should be focused to increase LCS awareness and uptake across the US to reduce lung cancer burden.
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The most common causes of acute hepatitis in children are hepatitis A and autoimmune hepatitis. Hepatitis in the course of Wilson's disease is sporadically registered in adolescents. An increase of activity of aminotransferases both in the course of multisystem inflammatory syndrome in children (MIS-C) and in the course of COVID-19 has been observed. Hepatitis is common in children with MIS-C and is associated with a more severe presentation and persistent elevation of liver function tests. To date, no cases of acute hepatitis in children due to COVID-19 have been reported. We present 2 cases of acute hepatitis in children where the only cause seems to be a previous asymptomatic SARS-CoV-2 infection.Copyright © 2023 Termedia Publishing House Ltd.. All rights reserved.
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Organ transplant recipients receive immunosuppressive drugs and hence are at high risk for COVID-19 due to their compromised immunity. This study assessed 1,370 liver transplant recipients who were followed at our hospital. A total of 12 patients got COVID-19: 5 recipients <50-years-old had mild disease, 7 recipients >60-years-old had moderate to severe disease, and 2 patients died. In addition, not all patients received 2 vaccinations, suggesting that the immunization is important for COVID-19 prophylaxis even in this patient population. One recipient was successfully treated with a combination of a reduced dose of immunosuppressive drugs, dexamethasone, remdesivir, and antibiotics, which is being established as an effective therapy for COVID-19.Copyright © 2022 The Japan Society of Hepatology.
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Among the longstanding problems made vivid by the COVID-19 pandemic are challenges in gathering data to inform the use of vaccines in pregnancy. Although it was known early on that pregnant persons and their offspring faced greater risks of morbidity and mortality from COVID-19 infection, they were excluded from all trials that led to authorization of vaccines. And while reassuring evidence has since been gathered, delays, as well as mixed public health messaging, have led to low uptake of vaccines among pregnant populations, as well as disproportionate burdens for pregnant persons. Dr. Lyerly will consider key ethical issues foregrounded by the COVID-19 response in pregnancy, including the distortions of risk, misaligned incentives, and regulatory challenges. Drawing on results of the NIH-funded PHASES Project, she will describe key conceptual shifts and ethical frameworks that have recently been advanced to better serve the interests of pregnant persons and their offspring facing illness in pandemic and other contexts, as well as specific recommendations for responsible and timely research with this population.
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Background: Only recently studies have been able to demonstrate the safety and efficacy of purification therapies in inflammatory diseases. Here we present the management of a young (21y) male patient in severe cardiogenic shock due to COVID-19 perymyocarditis admitted to the ICU at Bolzano Central Hospital. November 30th 2020 the patient developed high fever (>40 C) and diarrhea. After unsuccessfully being treated orally with a macrolide he was admitted to a peripheral hospital the 4th of December. The day after he deteriorated, required transfer to the ICU, endotracheal intubation and pharmacological cardiovascular support (Norepinephrine, Levosimendan). Antimicrobial treatment was started with piperacillin/tazobactam, linezolid and metronidazole. Despite multiple radiological and microbiological diagnostic attempts the origin of this severe septic shock remained unclear. December 6th the patient was transferred to Bolzano Central Hospital for VA-ECMO evaluation. Method(s): The transesophageal echocardiography revealed 15-20% of EF, lactate (5,2 mmol/l), cardiac enzymes (TropT 1400 mcg/l) and inflammatory parameters (PCT 35 ng/ml, IL-6 685 pg/ml) were elevated. We performed cardiac monitoring via Swan-Ganz catheter. The cardiac index was 1,6 l/min/m2. The peak dosage for Norepinephrine reached 7,5mg/h (1,47 mcg/kg/min). At Bolzano ICU we facilitate the pharmacological therapy with milrinone, vasopressin and low dose epinephrine. Furthermore, we impost continuous hemodiafiltration with CytoSorb filter. Result(s): Only hours after the start of filtration therapy the patient improved and we were able to gradually reduce catecholamine therapy, lactate values decreased. A VA-ECMO implantation was no more necessary. December 10th, we saw a stable patient without ventilatory or cardiovascular support, at echocardiography we revealed a normal EF. Conclusion(s): Clinically we saw a young patient in severe septic/cardiogenic shock due to perimyocarditis. Yet diagnostic attempts (CT-scan, multiple blood/urinary/liquor cultures) remained negative. Despite multiple negative PCR tests for SARS-CoV2 infection we performed specific immunoglobulin analysis and received a positive result for IgM. We therefore conclude on a COVID-19 associated perymyocarditis. Furthermore, this case illustrates the potential benefit of cytokine filtration and elimination in COVID-19 patients with altered IL6 levels.
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This paper examines the relevance of the use of a single irradiation of lungs in treatment of pneumonia caused by a new coronavirus infection. Clinical observations are presented that demonstrate perspectives in the treatment of this disease. Patients with severe pneumonia who were prescribed LD-RT (low-dose radiation therapy) at a dose of 0.5-1.5 Gy showed shorter recovery times and no complications. This method of treatment has shown its effectiveness in a number of studies from different countries, predicting success and economic benefits in its further use and study. A literature search containing information on relevant studies was carried out in PubMed, EMBASE, Web of Science and Google Scholar systems. Attention was focused on full-text articles given their general availability in a pandemic.Copyright © 2021 VIDAR Publishing House. All right reserved.
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Like the challenges and skepticism that faced the antibody therapeutics field over a decade ago, RNA therapeutics is facing the same. And, like the antibody therapeutics field, we are beginning to realize the clinical impact of RNA therapeutics amiss these challenges. This is most clearly highlighted with the recent approval of mRNA vaccines to prevent against SARS-CoV-2 and the first FDA approved RNAi drugs targeted to the liver. Unfortunately, RNA-based drugs targeted to cancer cells is lagging behind, even with countless years of work that has revealed the power of using RNAi for treating oncological diseases. Lack of success in this space is attributed to inability to deliver RNAi safely and effectively. A successful delivery agent requires multiple features. First, the agent must deliver the RNA specifically to the intended cells. Second, the agent must have a large therapeutic window, meaning that toxicity, if observed, should occur at doses that are orders of magnitude higher than the therapeutic dose. Third, if delivery of the RNA is by way of a specific ligand and receptor pair, as is the case herein, the RNA must successfully escape the endosome. Simply swelling the endosome is not enough if noncovalent interactions between the ligand and the receptor cannot be disrupted. Fourth, the RNA should include appropriate stabilizing modifications to increase intracellular half-life that will reduce dosing and cost. Through hard work and dedication in this space, we have come up with an inclusive, easily synthesized, intramolecular molecule that achieves all of these essential features. Moreover, the ligand used to achieve successful delivery is also being evaluated for imaging tumors localized in the central nervous system. Here, the challenges we face, the hurdles we have overcome, and the barriers that still remain to achieve success in revealing the clinical potential of miRNA as anti-cancer therapeutics will be presented.
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Aims and objectives: The aim of this study was to compare the immediate adverse effects of the coronavirus disease 2019 (COVID-19) vaccine (COVAXIN) in a pregnant woman with that of a nonpregnant woman. Material(s) and Method(s): It is a prospective observational study done at Vanivilas Hospital, Bangalore Medical College & Research Institute (BMCRI) for 2 months. The sample size was 100 pregnant and 100 nonpregnant women. Telephonically, patients were followed-up, and details of the side/adverse effects were collected in a proforma after 2 and 14 days. Data collected from both groups were analyzed using the Chi-square test or Fisher's exact test. Result(s): The majority of women were in the age group of <=25 years (64.0% and 36.0%, respectively) with a mean age of 25.01 +/- 3.71 years among the pregnant and 28.52 +/- 6.00 years among nonpregnant women. About 25.0% of pregnant women and 38.0% of nonpregnant women reported side effects. About 15.0% and 22.0% had taken treatment for side effects among pregnant women and nonpregnant women, respectively. Among the pregnant women, the common side effects reported were injection site pain (17) followed by fever (5), fatigue (4), and myalgia (03). Whereas among the nonpregnant women, the common side effects reported were injection site pain (28) followed by fever (6), myalgia (3), headache (2), and fatigue (1). Conclusion(s): Side effects reported following the administration of Covaxin in pregnant and nonpregnant women are fever, fatigue, injection site pain, myalgia, and headache. The proportion of side effects was not significantly different in the pregnant and nonpregnant women following Covaxin administration. Clinical significance: Covaxin is an inactivated killed vaccine against COVID-19 by Bharat Biotech. The vaccine has been recommended for pregnant women by the Government of India during corona pandemic. Studies are lacking regarding the difference in adverse events in pregnant versus nonpregnant women, after vaccine administration.Copyright © The Author(s).
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Background & Aim: Liposomes are spherical-shaped vesicles composed of one or more lipid bilayers. The ability of liposomes to encapsulate hydro- or lipophilic drugs allowed these vesicles to become a useful drug delivery system. Natural cell membranes, such as Bioxome, have newly emerged as new source of materials for molecular delivery systems. Bioxome are biocompatible and GMP-compliant liposome-like membrane that can be produced from more than 200 cell types. Bioxome self-assemble, with in-process self-loading capacity and can be loaded with a variety of therapeutic compounds. Once close to the target tissue, Bioxome naturally fuse with the cell membrane and release the inner compound. Orgenesis is interested in evaluating the potential of Bioxome as new drug delivery system for treatment of several diseases, including skin repair, local tumour or COVID19. Methods, Results & Conclusion(s): Bioxome were obtained from adipose- derived Mesenchymal Stem Cells, with a process of organic- solvent lipid extraction, followed by lyophilization and sonication assemblage. During the sonication process, Bioxome were charged or not with several cargos. Size distribution of empty Bioxome was detected by Particle Size Analyzer (NanoSight). Electron Microscopy (EM) was performed to assess Bioxome morphology. Lipid content was evaluated by electrospray ionization system. Dose response in vitro test on human lung fibroblasts treated or not with Bioxome encapsulating a specific cargo (API) against COVID19 were performed. NanoSight analysis showed that nanoparticle size in Bioxome samples ranged between 170+/-50 nm, with a concentration ranging between 109-1010+/-106 particles/mL. EM clearly showed the double phospholipid layers that composes the Bioxome. Stability study demonstrated that Bioxome are stable in size and concentration up to 90 days at +4Cdegree or even at RT. No change in size between encapsulated Bioxome with small size (~340 Da) cargo vs empty Bioxome was observed up to 30 days storage. Lipidomic analysis approach revealed that the yield of lipids and their composition are satisfactory for a therapeutic product using Bioxome. Lastly, in the in vitro model of COVID19, Bioxome encapsulating API effectively saved cells from death (20x vs untreated cells) and at lower doses of API than these of non-encapsulated cargo (0.005 microM vs 0.1 microM). Bioxome seems to be an excellent candidate for liposome mimetic tool as drug delivery system for targeting specific organs and diseases treatment.Copyright © 2023 International Society for Cell & Gene Therapy
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Objectives: According to the CDC, as of December 2022, almost one in three Americans had confirmed COVID-19 infection;yet only a small portion generated healthcare claims related to COVID-19. Higher burden of COVID-19 cases in Northeastern states compared to other US regions has been documented. This study examined the regional variation in demographic characteristics and treatment patterns among patients with a claim for COVID-19 in a nationwide US claims database. Method(s): Analysis of data from over 277 million patients in IQVIA's longitudinal medical and pharmacy claims databases resulted in a cohort of 17,682,111 patients with COVID-19 diagnosis between 4/1/2020 and 4/30/2022. Demographic characteristics and treatment rates for key approved and un-approved COVID-19 therapies were assessed and stratified by region. Result(s): Among patients in the database, 6.4% had a COVID-19 diagnosis. The proportion was higher in the Northeast (7.1%) and South (6.9%) compared with the West (4.8%). The highest proportion of patients were aged 18-44 years (32.7% in South to 35.2% in West). Over a fifth of the patients were >= 65 years old (US overall= 23.7%;22.5% in Northeast to 25.8% in Midwest). Approximately 57% of the patients nationally and within each region were women. For approved medications, utilization ranged from 1.7% in Northeast to 2.7% in Midwest (overall:2.2%) for remdesivir;0.7% in Northeast to 2.2% in South (overall: 1.5%) for casirivimab/imdevimab. For unapproved medications, utilization ranged from 0.9% in Northeast to 1.6% in South (overall:1.3%) for hydroxychloroquine and 0.4% in Northeast to 1.8% in South (overall:1.1%) for ivermectin. Conclusion(s): Less than one in five US cases of COVID-19 had a claim with diagnosis of COVID-19. Use of COVID-19 specific medications remained low throughout the pandemic. Despite the higher disease burden, proportion of patients with claims and receiving COVID-19 treatment were low nationally, particularly in the northeast US region.Copyright © 2023
ABSTRACT
Background: B-cell lymphoma-2 (Bcl-2) proteins play an important role in multiple myeloma (MM) cell survival and represent an attractive therapeutic target. In prior trials, a subgroup analysis of patients with t(11;14)-positive relapsed/refractory (R/R) MM showed the combination of a Bcl-2 inhibitor, a proteasome inhibitor, and dexamethasone improved progression-free survival with no increased mortality. BGB-11417, a Bcl-2 inhibitor, is more potent and selective than venetoclax. BGB-11417- 105 (NCT04973605) is a phase 1b/2 study assessing the safety and efficacy of BGB-11417 monotherapy, in combination with dexamethasone, or with dexamethasone+carfilzomib in patients with t(11;14)-positive R/R MM. Preliminary safety results for the combination of BGB-11417 + dexamethasone are presented. Method(s): Eligible patients had t(11;14)-positive R/R MM and had been exposed to a proteasome inhibitor, immunomodulatory agent, and anti-CD38 therapy. Patients received 80-, 160-, 320-, or 640-mg BGB-11417 daily with 40-mg dexamethasone weekly until death, intolerability, or disease progression. Dose escalation was guided by a mTPI-2 design and overall review by a safety monitoring committee. Pharmacokinetics (PK) were also assessed. Result(s): As of 1 July 2022, 10 patients were enrolled in the 80-, 160-, and 320-mg (3 patients each) and 640-mg (1 patient) dose-escalation cohorts of BGB-11417 + dexamethasone. The median age was 69 years (range, 52-81) and median prior lines of therapy was 3 (range, 1-5). The median treatment duration was 3.2 months (range, 0.5-6.5). No patients experienced dose-limiting toxicity at any dose level. Three patients died whilst on study: 1 due to COVID-19 complications 157 days after treatment discontinuation (day 208), 1 due to progressive disease 50 days after treatment discontinuation (day 89), and 1 due to COVID-19 whilst on study treatment (day 78). No deaths were associated with study treatment. Two patients experienced Grade >= 3 treatment-emergent adverse events (TEAEs). One patient in the 160-mg cohort experienced Grade 3 increase in liver enzymes and lymphopenia. One patient in the 320-mg cohort experienced Grade 3 lymphopenia. The most common TEAEs were insomnia (50%), fatigue (30%), arthralgia (20%), back pain (20%), lymphopenia (20%), and nausea (20%). BGB-11417 exposure increased dose-dependently from 80 mg to 320 mg with high interpatient PK variability. BGB-11417 exposures after single and multiple doses appeared similar, indicating limited accumulation. Conclusion(s): BGB-11417 plus dexamethasone was generally well-tolerated in patients with R/R MM harbouring t(11;14) at doses <=640 mg. Efficacy data are forthcoming. Recruitment is ongoing in the US, Australia, and New Zealand;the BGB-11417, dexamethasone, and carfilzomib combination arm will open in the future.
ABSTRACT
Radiotherapy-induced secondary malignancy is a well-known occurrence. During the COVID-19 pandemic, many people have undergone serial computed tomography (CT) imaging, and concerns have been raised regarding radiation-induced malignancies due to frequent scanning. Accordingly, various low and ultra-low-dose CT (LDCT) thorax protocols have been developed to reduce the dose of radiation. Major governing bodies worldwide have established guidelines regarding the indications for CT scans and chest X-rays during the pandemic. We, therefore, aimed to provide facts about the effects of radiation (both diagnostic and therapeutic). Through this article, we intend to break the myths and 'mithya' (misbeliefs) regarding diagnostic radiation and its association with cancer in this COVID-19 era. For this review, we performed a search in Google using specific keywords pertaining to imaging during COVID-19 and radiation risk. We also included the names of various global governing bodies in the Google search. We included only full text articles and guidelines from authentic websites. From this review, we conclude that if we follow the recommendations of various global governing bodies and use CT scan only in cases of moderate to severe COVID-related symptoms, adhere to the principle of 'as low as reasonably achievable' for radiation protection, and use LDCT scan protocols, we can significantly reduce the mean effective radiation dose delivered and the estimated cancer risk.Copyright © 2023 Cancer Research, Statistics, and Treatment. All rights reserved.
ABSTRACT
BACKGROUND: The increased number of computed tomography scans during the COVID-19 pandemic has emphasized the task of decreasing radiation exposure of patients, since it is known to be associated with an elevated risk of cancer development. The ALARA (as low as reasonably achievable) principle, proposed by the International Commission on Radiation Protection, should be adhered to in the operation of radiation diagnostics departments, even during the pandemic. AIM: To systematize data on the appropriateness and effectiveness of low-dose computed tomography in the diagnosis of lung lesions in COVID-19. MATERIALS AND METHODS: Relevant national and foreign literature in scientific libraries PubMed and eLIBRARY, using English and Russian queries "low-dose computed tomography” and "COVID-19,” published between 2020 and 2022 were analyzed. Publications were evaluated after assessing the relevance to the review topic by title and analysis. The references were further analyzed to identify articles omitted during the search that may meet the inclusion criteria. RESULTS: Published studies summarized the current data on the imaging of COVID-19 lung lesions and the use of computed tomography scans and identified possible options for reducing the effective dose. CONCLUSION: We present techniques to reduce radiation exposure during chest computed tomography and preserve high-quality diagnostic images potentially sufficient for reliable detection of COVID-19 signs. Reducing radiation dose is a valid approach to obtain relevant diagnostic information, preserving opportunities for the introduction of advanced computational analysis technologies in clinical practice. © Eco-Vector, 2023.