Arch Argent Pediatr. 2021 Jun;119(2):e234-e238. doi: 10.5546/aap.2021.e234.

ABSTRACT

Drug reaction with eosinophilia and systemic symptoms or DRESS syndrome is among severe cutaneous drug reactions. This constitutes a clinical triad that includes fever, skin rash and systemic compromise, accompanied by eosinophilia and/ or atypical lymphocytes. We present the case of an 18-month-old female patient with cystic fibrosis, who develops this pathology during a trimethoprim-sulfamethoxazole cycle as an eradicating treatment of methicillin-resistant Staphylococcus aureus in bronchial secretions. Cystic fibrosis patients receive multiple antibiotic regimens according to bacteriology in sputum, to avoid impairment in their lung function and colonization by resistant germs. Due to the increased risk of drug hypersensitivity in cystic fibrosis, an ominous prognosis and high morbidity and mortality, knowledge and a high index of suspicion of this syndrome are necessary.

PMID:34033428 | DOI:10.5546/aap.2021.e234

Thorac Cancer. 2021 May 25. doi: 10.1111/1759-7714.14040. Online ahead of print.

ABSTRACT

Air leakage is a common complication after pulmonary resection, and fibrin glue is used as a sealant to reduce postoperative air leakage. It is generally recognized that fibrin glue-induced adverse events are rare. Herein, we report a rare case of suspected fibrin glue-induced acute eosinophilic pneumonia (AEP). A 72-year-old man underwent right lower lobectomy and mediastinal lymph node dissection for right lower lung cancer. Fibrin glue was sprayed to cover the interlobar surface of the right upper and middle lobes. On postoperative day 10, computed tomography (CT) revealed ground-glass shadows around the interlobar surface of the remaining lobes of the right lung. Although antibacterial drugs were administered for suspected bacterial pneumonia, fever spike, shortness of breath, and exacerbation of ground-glass shadows were observed. Peripheral blood and bronchoalveolar lavage fluid showed increased eosinophil count, supporting the diagnosis of AEP. Pneumonia resolved after prednisolone administration. At one-year follow-up, CT showed no AEP recurrence. Drug-induced pneumonia usually develops in the bilateral lung and rarely in the hemilateral lung. In this case, pneumonia was localized around the site covered with fibrin glue, suggesting fibrin glue-induced AEP. Thus, the use of fibrin glue should be carefully considered during pulmonary resection.

PMID:34033235 | DOI:10.1111/1759-7714.14040

Diabetes Obes Metab. 2021 May 25. doi: 10.1111/dom.14448. Online ahead of print.

ABSTRACT

AIMS: To assess the efficacy, safety, and tolerability of ipragliflozin 50 mg once daily (q.d.) added to sitagliptin 50 mg q.d. monotherapy in Japanese patients with type 2 diabetes (T2D).

MATERIALS AND METHODS: The results of two clinical trials are reported. In both, patients had HbA1c 7.0-10.0% on sitagliptin 50 mg q.d. 2 weeks prior to addition of ipragliflozin or placebo. In one trial (843), patients were randomized 1:1 to addition of blinded ipragliflozin 50 mg q.d. (n=73) or placebo (n=70) for 24 weeks; the primary endpoint was efficacy (change in HbA1c at Week 24). In the other trial (849), open-label ipragliflozin 50 mg q.d. was added for 52 weeks (n=77); the primary objective was to assess safety/tolerability.

RESULTS: In trial 843, baseline characteristics were similar between groups (mean age 60.5 years, HbA1c 8.0%); after 24 weeks, adding ipragliflozin provided significantly greater reduction in HbA1c compared to placebo: least squares (LS) mean difference (95% confidence interval) -0.77% (-0.98, -0.57), p<0.001. In 843, the incidences of adverse events (AEs) overall and prespecified AEs of clinical interest (symptomatic hypoglycemia, urinary tract infection, genital infection, hypovolemia, and polyuria/pollakiuria) were similar between groups. In trial 849, specific AEs with incidence ≥5% were nasopharyngitis, pollakiuria, back pain, thirst, constipation, influenza, and arthralgia; drug-related AEs reported in ≥2 patients were pollakiuria, thirst, and constipation. In 849, no serious drug-related AE was reported.

CONCLUSIONS: Ipragliflozin 50 mg q.d. added on to sitagliptin 50 mg q.d. monotherapy provided significant improvement in glycemic control and was generally well tolerated in Japanese patients with T2D. CLINICAL TRIALS.GOV: NCT02577003/NCT02564211 This article is protected by copyright. All rights reserved.

PMID:34033212 | DOI:10.1111/dom.14448

J Clin Pharmacol. 2021 May 25. doi: 10.1002/jcph.1916. Online ahead of print.

ABSTRACT

Adverse drug reactions (ADRs) are common, yet are often underreported making them difficult to track and study. Prospective pharmacovigilance programs significantly increase detection and reporting of ADRs. The aim of this pilot study was to apply triggers used by a prospective pharmacovigilance program at a free-standing children's hospital to retrospectively detect ADRs at our institution, therefore determining if these methods could be replicated and provide the basis for implementation of a prospective pharmacovigilance program. In 2019, our institution had 22,000 inpatient admissions and 51,000 emergency room visits and had 21 ADRs voluntarily reported in an electronic medication safety tracking system. Additional ADRs were identified by methods including new or modifications to the patient's allergy profile in the electronic medical record (EMR) and International Classification of Disease (ICD) codes. We identified 754 unique patients with changes to allergy profile and 5,719 ICD codes in 3,966 unique patients to evaluate. These triggers prompted screening of the EMR to validate the ADR, and we identified 280 ADRs occurring in 2019. Eight (2.8%) were identified solely by the electronic medication safety tracking system, 64 (23%) were identified by the allergy list, 110 (39%) were identified only by ICD coding, and the remaining 98 (35%) were identified by multiple methods. The use of triggers followed by review of the EMR identified thirteen-fold more ADRs than were voluntarily reported, illustrating the need for an active pharmacovigilance service and the successful use of multi-modal methods to detect and track ADRs. This article is protected by copyright. All rights reserved.

PMID:34031886 | DOI:10.1002/jcph.1916

Eur J Hosp Pharm. 2021 May 24:ejhpharm-2021-002794. doi: 10.1136/ejhpharm-2021-002794. Online ahead of print.

NO ABSTRACT

PMID:34031153 | DOI:10.1136/ejhpharm-2021-002794

Yakugaku Zasshi. 2021 May 24. doi: 10.1248/yakushi.21-00001. Online ahead of print.

ABSTRACT

Previous studies have reported the inappropriate administration of medication at nursery schools by the staff and a lack of drug-related information from caregivers at the time of request. However, the situation concerning medication administration at nursery schools from the mothers' perspective is unknown and it is not clear what information the mothers provided to nursery staff at the request. We conducted an online survey between April and May 2019 regarding the administration of medication at the nursery school with input from 600 mothers. Overall, 510 (85%) individuals replied that the requests to administer medication were acceptable for all or some of the medications. Application forms for medications were used by 91% of the 301 mothers who had previously made such requests. Although information including the child's name, medication times, illness of the child, parent's name, and dosage form was specified by over 70% of mothers, drug-related information such as effectiveness, side effects, and drug interactions was insufficient. In total, 41 instances of inappropriate medication administration by staff were reported by 35 mothers. It is suggested that the drug information sheets provided by community pharmacies should make up for inadequate drug-related information on application forms for medications to avoid the risk of adverse events and reduce staff burden. Toward this end, it is necessary to provide easily understandable information sheets for nursery staff, as the medication is usually administered by nursery staff, not a nurse. Community pharmacists should support these measures as pharmaceutical professionals.

PMID:34024877 | DOI:10.1248/yakushi.21-00001

Expert Opin Drug Saf. 2021 May 21. doi: 10.1080/14740338.2021.1931115. Online ahead of print.

ABSTRACT

INTRODUCTION: Different single-tablet regimens (STRs), containing one or two nucleoside reverse transcriptase inhibitors (NRTIs) plus an anchor drug, are available for the use in naïve, HIV-infected patients. Despite some restrictions in the use of particular regimens in certain situations (e.g. HBV coinfection), International guidelines do not provide indications to prefer any regimen over others concerning the tolerability profile. We aimed to assess advantages and disadvantages of the most prescribed STRs.

AREAS COVERED: An extensive review of articles published in English language was conducted on PubMed, looking for evidence about single-tablet regimens in naïve, HIV-infected population. Safety outcomes of registrational trials were assessed, giving priority to studies directly comparing STRs included in our research (abacavir/lamivudine/dolutegravir, tenofovir alafenamide/emtricitabine/bictegravir, lamivudine/dolutegravir, tenofovir alafenamide/emtricitabine/darunavir/cobicistat, tenovofir disoproxil fumarate/lamivudine/doravirine). Data from cohort studies and meta-analyses were also assessed, extrapolating the main evidence about the combinations of interest.

EXPERT OPINION: Integrase inhibitors (InsTIs)-based regimens have few interruptions for adverse events and few drug-related adverse events, with tenofovir alafenamide/emtricitabine/dolutegravir and lamivudine/dolutegravir being the most tolerable ones. However, neuropsychiatric adverse events and metabolic issues could prompt the alternative use of darunavir or doravirine-based combinations, even if a superior safety profile of these combinations over InSTIs has yet to be demonstrated.

PMID:34018892 | DOI:10.1080/14740338.2021.1931115

Drug Ther Bull. 2021 May 20:dtb-2021-000024. doi: 10.1136/dtb.2021.000024. Online ahead of print.

NO ABSTRACT

PMID:34016639 | DOI:10.1136/dtb.2021.000024

Neuroimage Clin. 2021 Apr 15;30:102672. doi: 10.1016/j.nicl.2021.102672. Online ahead of print.

ABSTRACT

Ibudilast (MN-166) is an inhibitor of macrophage migration inhibitory factor (MIF) and phosphodiesterases 3,4,10 and 11 (Gibson et al., 2006; Cho et al., 2010). Ibudilast attenuates CNS microglial activation and secretion of pro-inflammatory cytokines (Fujimoto et al., 1999; Cho et al., 2010). In vitro evidence suggests that ibudilast is neuroprotective by suppressing neuronal cell death induced by microglial activation. People with ALS have increased microglial activation measured by [11C]PBR28-PET in the motor cortices. The primary objective is to determine the impact of ibudilast on reducing glial activation and neuroaxonal loss in ALS, measured by PBR28-PET and serum Neurofilament light (NfL). The secondary objectives included determining safety and tolerability of ibudilast high dosage (up to 100 mg/day) over 36 weeks. In this open label trial, 35 eligible ALS participants underwent ibudilast treatment up to 100 mg/day for 36 weeks. Of these, 30 participants were enrolled in the main study cohort and were included in biomarker, safety and tolerability analyses. Five additional participants were enrolled in the expanded access arm, who did not meet imaging eligibility criteria and were included in the safety and tolerability analyses. The primary endpoints were median change from baseline in (a) PBR28-PET uptake in primary motor cortices, measured by standard uptake value ratio (SUVR) over 12-24 weeks and (b) serum NfL over 36-40 weeks. The secondary safety and tolerability endpoints were collected through Week 40. The baseline median (range) of PBR28-PET SUVR was 1.033 (0.847, 1.170) and NfL was 60.3 (33.1, 219.3) pg/ml. Participants who completed both pre and post-treatment scans had PBR28-PET SUVR median(range) change from baseline of 0.002 (-0.184, 0.156) , P = 0.5 (n = 22). The median(range) NfL change from baseline was 0.4 pg/ml (-1.8, 17.5), P = 0.2 (n = 10 participants). 30(86%) participants experienced at least one, possibly study drug related adverse event. 13(37%) participants could not tolerate 100 mg/day and underwent dose reduction to 60-80 mg/day and 11(31%) participants discontinued study drug early due to drug related adverse events. The study concludes that following treatment with ibudilast up to 100 mg/day in ALS participants, there were no significant reductions in (a) motor cortical glial activation measured by PBR28-PET SUVR over 12-24 weeks or (b) CNS neuroaxonal loss, measured by serum NfL over 36-40 weeks. Dose reductions and discontinuations due to treatment emergent adverse events were common at this dosage in ALS participants. Future pharmacokinetic and dose-finding studies of ibudilast would help better understand tolerability and target engagement in ALS.

PMID:34016561 | DOI:10.1016/j.nicl.2021.102672

Brief Bioinform. 2021 May 19:bbab161. doi: 10.1093/bib/bbab161. Online ahead of print.

ABSTRACT

The basis of several recent methods for drug repurposing is the key principle that an efficacious drug will reverse the disease molecular 'signature' with minimal side effects. This principle was defined and popularized by the influential 'connectivity map' study in 2006 regarding reversal relationships between disease- and drug-induced gene expression profiles, quantified by a disease-drug 'connectivity score.' Over the past 15 years, several studies have proposed variations in calculating connectivity scores toward improving accuracy and robustness in light of massive growth in reference drug profiles. However, these variations have been formulated inconsistently using various notations and terminologies even though they are based on a common set of conceptual and statistical ideas. Therefore, we present a systematic reconciliation of multiple disease-drug similarity metrics ($ES$, $css$, $Sum$, $Cosine$, $XSum$, $XCor$, $XSpe$, $XCos$, $EWCos$) and connectivity scores ($CS$, $RGES$, $NCS$, $WCS$, $Tau$, $CSS$, $EMUDRA$) by defining them using consistent notation and terminology. In addition to providing clarity and deeper insights, this coherent definition of connectivity scores and their relationships provides a unified scheme that newer methods can adopt, enabling the computational drug-development community to compare and investigate different approaches easily. To facilitate the continuous and transparent integration of newer methods, this article will be available as a live document (https://jravilab.github.io/connectivity_scores) coupled with a GitHub repository (https://github.com/jravilab/connectivity_scores) that any researcher can build on and push changes to.

PMID:34013329 | DOI:10.1093/bib/bbab161

Eur J Hosp Pharm. 2021 May 19:ejhpharm-2021-002805. doi: 10.1136/ejhpharm-2021-002805. Online ahead of print.

ABSTRACT

We report the case of a man in his early 70s with idiopathic acquired haemophilia A and persistent high-titre type II inhibitors on immunosuppressive treatment to eradicate the inhibitor. As complications, he had a nosocomial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which caused severe pneumonia and an explosive inflammatory reaction that required tocilizumab and remdesivir treatment, and a high-risk retroperitoneal haematoma. Recombinant porcine factor VIII, susoctocog alfa, was requested from the Pharmacy Service in view of the extreme risk of thromboembolism resulting from the concomitant inflammatory storm caused by SARS-CoV-2. Improvement in the SARS-CoV-2 infection made it possible to complete the immunosuppressive treatment with rituximab. The patient was discharged with mycophenolate mofetil as immunosuppressive treatment after 89 days in hospital and 22 days of treatment with susoctocog alfa. His SARS-CoV-2 infection resolved and the haematoma evolved favourably.

PMID:34011555 | DOI:10.1136/ejhpharm-2021-002805

Future Oncol. 2021 May 20. doi: 10.2217/fon-2021-0266. Online ahead of print.

ABSTRACT

Aim: We report real-world evidence with regorafenib in previously treated metastatic colorectal cancer from the French cohort of the international, prospective, observational CORRELATE study. Patients & methods: Patients receiving regorafenib according to French health authority approval were included. The primary end point was treatment-emergent adverse events. Overall survival and progression-free survival were secondary end points. Results: Two hundred and forty-two patients (61% male, median age: 66 years) were enrolled. The most common grade ≥3 drug-related treatment-emergent adverse events were hand-foot skin reaction (10.3%), asthenia/fatigue (9.9/1.2%) and hypertension (6.2%). Median overall survival and progression-free survival were 6.8 (95% CI: 6.3-7.6) and 2.8 months (95% CI: 2.6-3.0), respectively. Conclusion: The real-world safety and effectiveness data of regorafenib in metastatic colorectal cancer in France align with findings from Phase III clinical trials and the global CORRELATE population.

PMID:34011165 | DOI:10.2217/fon-2021-0266

Am J Health Syst Pharm. 2021 May 19:zxab211. doi: 10.1093/ajhp/zxab211. Online ahead of print.

ABSTRACT

DISCLAIMER: In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

PURPOSE: Cost-avoidance studies of pharmacist interventions are common and often the first type of study conducted by investigators to quantify the economic impact of clinical pharmacy services. The purpose of this primer is to provide guidance for conducting cost-avoidance studies pertaining to clinical pharmacy practice.

SUMMARY: Cost-avoidance studies represent a paradigm conceptually different from traditional pharmacoeconomic analysis. A cost-avoidance study reports on cost savings from a given intervention, where the savings is estimated based on a counterfactual scenario. Investigators need to determine what specifically would have happened to the patient if the intervention did not occur. This assessment can be fundamentally flawed, depending on underlying assumptions regarding the pharmacists' action and the patient trajectory. It requires careful identification of the potential consequence of nonaction, as well as probability and cost assessment. Given the uncertainty of assumptions, sensitivity analyses should be performed. A step-by-step methodology, formula for calculations, and best practice guidance is provided.

CONCLUSIONS: Cost-avoidance studies focused on pharmacist interventions should be considered low-level evidence. These studies are acceptable to provide pilot data for the planning of future clinical trials. The guidance provided in this article should be followed to improve the quality and validity of such investigations.

PMID:34007979 | DOI:10.1093/ajhp/zxab211

Innov Pharm. 2020 Jul 31;11(3). doi: 10.24926/iip.v11i3.3315. eCollection 2020.

ABSTRACT

Introduction: Product switching followed by suspected adverse events are common and unsettling for antiepileptic drugs. The objective of this case study was to describe the investigation performed after report of suspected therapeutic failure in pediatric patients following a switch to a different valproate manufacturer and identify strategies concerning medication management for improving therapeutic outcomes. Case description: It was reported that different pediatric patients' condition changed (agitation/ seizures) after refilling the same drug prescription (sodium valproate syrup) from a different manufacturer. Medical staff reported a suspected therapeutic failure and some units of the product batch associated with the problem were seized by the local Post-marketing Surveillance Service for investigation of potential quality deviations. The seized units were evaluated by the State's Surveillance Laboratory, nevertheless, drug potency was found to be 98.7%. Conclusion: We consider that the reported event could be associated with aspects of medication use, i.e. potential dose measurement deviations resulting from remaining of residual liquid in the cup or eventual delay at prescription refilling process and consequential - even though brief - pharmacotherapy discontinuity. Patient education and counseling by pharmacists are essential for preventing drug-related problems and enhancing positive outcomes of pharmacotherapy.

PMID:34007631 | PMC:PMC8075144 | DOI:10.24926/iip.v11i3.3315

Am J Health Syst Pharm. 2021 May 18:zxab214. doi: 10.1093/ajhp/zxab214. Online ahead of print.

ABSTRACT

PURPOSE: Cost-avoidance studies are common in pharmacy practice literature. This scoping review summarizes, critiques, and identifies current limitations of the methods that have been used to determine cost avoidance associated with pharmacists' interventions in acute care settings.

METHODS: An Embase and MEDLINE search was conducted to identify studies that estimated cost avoidance from pharmacist interventions in acute care settings. We included studies with human participants and articles published in English from July 2010 to January 2021, with the intent of summarizing the evidence most relevant to contemporary practice.

RESULTS: The database search retrieved 129 articles, of which 39 were included. Among these publications, less than half (18 of 39) mentioned whether the researchers assigned a probability for the occurrence of a harmful consequence in the absence of an intervention; thus, a 100% probability of a harmful consequence was assumed. Eleven of the 39 articles identified the specific harm that would occur in the absence of intervention. No clear methods of estimating cost avoidance could be identified for 7 studies. Among all 39 included articles, only 1 attributed both a probability to the potential harm and identified the cost specific to that harm.

CONCLUSION: Cost-avoidance studies of pharmacists' interventions in acute care settings over the last decade have common flaws and provide estimates that are likely to be inflated. There is a need for guidance on consistent methodology for such investigations for reporting of results and to confirm the validity of their economic implications.

PMID:34003209 | DOI:10.1093/ajhp/zxab214

Rev Med Suisse. 2021 May 12;17(738):948-949.

NO ABSTRACT

PMID:33998195

Cannabis Cannabinoid Res. 2020 Oct 21. doi: 10.1089/can.2020.0059. Online ahead of print.

ABSTRACT

Introduction: Overdose fatalities associated with the opioid epidemic are predictably attributable to drug-induced respiratory depression. In terms of illicit opioid abuse, fentanyl is the synthetic opioid responsible for the largest number of overdose deaths. There is, therefore, an urgent need to identify safe and effective therapeutics that can attenuate fentanyl-induced respiratory depression. Identification of effective alternate analgesic strategies that lessen the respiratory depression associated with narcotics would also help improve current strategies for pain management. Our laboratory recently reported that the G protein-biased CB2 cannabinoid receptor agonist LY2828360 suppressed chemotherapy-induced neuropathic nociception and attenuated both morphine tolerance and physical dependence in paclitaxel-treated mice. However, the impact of LY2828360 on other undesirable side effects of opioids, such as opioid-induced respiratory depression, remains unknown. Materials and Methods: We used whole-body plethysmography to assess the impact of the CB2 cannabinoid agonist LY2828360 on fentanyl-induced respiratory depression using wild-type (WT) and CB2 knockout (CB2KO) mice. Results: Fentanyl reduced minute ventilation and respiratory frequency without altering tidal volume in both WT and CB2KO mice. In WT mice, the high dose of fentanyl (0.2 mg/kg intraperitoneal [i.p.]) produced a greater suppression of respiratory parameters compared with the low dose of fentanyl (0.1 mg/kg i.p.). Coadministration of a behaviorally active dose of LY2828360 (3 mg/kg i.p.) with fentanyl (0.2 mg/kg i.p.) attenuated fentanyl-induced respiratory depression in WT mice. Notably, LY2828360 (3 mg/kg i.p.) did not attenuate fentanyl-induced respiratory depression in CB2KO mice, consistent with mediation by CB2 receptors. Moreover, LY2828360 (3 mg/kg i.p.) alone lacked intrinsic effects on respiratory parameters in either WT or CB2KO mice. Conclusion: The combination of a CB2 agonist with fentanyl may represent a safer adjunctive therapeutic strategy compared with a narcotic analgesic alone by attenuating the development of opioid-induced respiratory depression. Moreover, the CB2 agonist, administered alone, did not alter respiration. Our findings suggest that the CB2 cannabinoid agonist LY2828360 may provide CB2-mediated protection against fentanyl-induced respiratory depression, a detrimental and unwanted side effect of opioid use and abuse.

PMID:33998863 | DOI:10.1089/can.2020.0059

Front Oncol. 2021 Apr 30;11:681997. doi: 10.3389/fonc.2021.681997. eCollection 2021.

ABSTRACT

Currently, only a few reports exist on the cytokine release syndrome (CRS) as one of the severe immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs). Notably, it is very rare that grade 4 CRS related to ICI therapy overlaps with the drug-induced hypersensitivity syndrome (DiHS). A 46-year old woman with metastatic kidney cancer had grade 3 interstitial pneumonitis induced by four cycles of combination therapy of anti-programmed death-1 and anti-cytotoxic T lymphocyte-4 antibodies after right cytoreductive nephrectomy. Prophylactic administration of trimethoprim/sulfamethoxazole (TMP/SMX) was started concomitantly with prednisolone therapy to treat the interstitial pneumonitis. She developed hypotensive shock when reducing the dosage of prednisolone, and required intubation and ventilation using vasopressors at the intensive care unit. She subsequently exhibited prominent leukocytosis and an increased level of C-reactive protein, suggesting markedly increased cytokine levels. Interestingly, facial edema and erythema increased in association with pyrexia, leukocytosis, liver dysfunction, and renal failure, suggesting that she developed DiHS. She received hemodialysis three times, a plasma exchange, and anti-interleukin-6 therapy to treat severe renal dysfunction, a thrombotic thrombocytopenic purpura-suspected condition, and possible grade 4 CRS, respectively. Although these therapies did not elicit sufficient effects, high-dose administration of intravenous immunoglobulin was successful. With steroid mini-pulse therapy and the subsequent administration of prednisolone, she recovered successfully. To the best of our knowledge, this is the first report that ICIs and TMP/SMX can induce hypotensive shock accompanied with CRS and DiHS during immunosuppressive therapy for an irAE. Importantly, the prophylactic administration of TMP/SMX should be performed cautiously to avoid severe drug reactions such as CRS or DiHS.

PMID:33996612 | PMC:PMC8121494 | DOI:10.3389/fonc.2021.681997

World Allergy Organ J. 2021 Apr 22;14(4):100535. doi: 10.1016/j.waojou.2021.100535. eCollection 2021 Apr.

ABSTRACT

BACKGROUND: Hereditary angioedema (HAE) due to C1 esterase inhibitor deficiency (C1-INH-HAE) is characterized by recurrent swelling attacks. A European treatment registry was established to review the adverse event profile and efficacy of recombinant human C1 esterase inhibitor (rhC1-INH) for HAE attacks.

METHODS: Individuals with C1-INH-HAE were enrolled following a decision to treat with rhC1-INH and provision of written informed consent. Medical history and baseline HAE information were collected at screening. Healthcare providers entered data on HAE attacks, response to treatment, and adverse events using a web-based questionnaire.

RESULTS: From July 1, 2011, through December 1, 2019, 71 patients with C1-INH-HAE (30 male/41 female; mean age, 47.3 years; age range, 19-78 years) in 9 countries reported 2356 attacks and were treated with rhC1-INH. Before registry entry, patients, including 20 (28.2%) who were on maintenance therapy/prophylaxis at registry enrollment, experienced a mean of 25 HAE attacks per year (median, 16 [range, 0-185]). Most treated HAE attacks were abdominal (46.1%), followed by peripheral (38.3%), oro-facial-pharyngeal (14.8%), urogenital (3.2%), and laryngeal (2.6%). The mean rhC1-INH dose was 3307 U (43.3 U/kg). Patients reported symptom improvement within 4 h for 97.8% of attacks (2305/2356) with rhC1-INH; most attacks (99.8%; 2351/2356) required only 1 dose. Five attacks were treated with a second dose (total rhC1-INH dose administered for attack, 4200 U). No hypersensitivity, thrombotic/thromboembolic events, or drug-related serious adverse events were reported.

CONCLUSION: The rhC1-INH treatment registry provided real-world data on the treatment of 2356 HAE attacks that were consistent with clinical trial data of rhC1-INH in patients with C1-INH-HAE.

PMID:33995818 | PMC:PMC8093463 | DOI:10.1016/j.waojou.2021.100535

Front Pharmacol. 2021 Apr 29;12:654986. doi: 10.3389/fphar.2021.654986. eCollection 2021.

ABSTRACT

Liver cancer is the sixth most commonly diagnosed cancer and the fourth leading cause of cancer death. Most (75-85%) primary liver cancers occurring worldwide are hepatocellular carcinoma (HCC). The development of resistance and other drug related side effects are the prime reasons for the failure of treatment. Therefore, developing high-efficacy and low-toxicity natural anticancer agents is greatly needed in the treatment of HCC. Dihydrotanshinone (DHTS) is widely used for promoting blood circulation and antitumor. The aim of the present study was to investigate the effect and mechanism of DHTS-induced apoptosis of HCC, both in vitro and in vivo. We found that DHTS inhibited the growth of several HCC cells (HCCLM3, SMMC7721, Hep3B and HepG2). DHTS induced the apoptosis of SMMC7721 cells. Immunofluorescence results have showed that DHTS decreased STAT3 nuclear translocation. Moreover, Western blot results have demonstrated that DHTS suppressed the activation of JAK2/STAT3 signaling pathway. In addition, xenograft results have showed that DHTS suppressed tumor growth of SMMC7721 cells in vivo by inhibiting the p-STAT3. Thus, we demonstrated that DHTS could inhibit HCC by suppressing the JAK2/STAT3 pathway. DHTS has potential to be a chemotherapeutic agent in HCC and merits further clinical investigation.

PMID:33995073 | PMC:PMC8117156 | DOI:10.3389/fphar.2021.654986