Indian J Ophthalmol. 2023 Jan;71(1):235-240. doi: 10.4103/ijo.IJO_945_22.

ABSTRACT

PURPOSE: Our study aims to evaluate the effectiveness of intravenous erythropoietin (EPO) in patients with indirect traumatic optic neuropathy (TON), assess the side effects, and compare the visual function results among three groups of patients who had received different treatment options - EPO, steroids, and observation.

METHODS: : Patients with indirect TON presenting to the neuro-ophthalmology clinic from August 2019 to March 2020, were assigned to three groups, with six patients in each group. In group 1, patients were recruited prospectively and received recombinant human erythropoietin, whereas, in groups 2 and 3, patients were recruited retrospectively and received intravenous methylprednisolone followed by oral steroids and multivitamins, respectively. Groups 1 and 2 included patients presenting within 2 weeks of trauma, whereas group 3 included those presenting beyond that. Best-corrected visual acuity, pupillary reaction, color vision, and visual fields following treatment were measured.

RESULTS: Initial visual acuity in the EPO group ranged from 20/80 to no perception of light (No PL). The mean initial BCVA (1.82 logMAR, standard deviation [SD] = 0.847) improved to 1.32, SD = 0.93 logMAR after treatment recorded at the third month (P = 0.0375), with no significant adverse effects. The initial BCVA of group 2 ranged from 20/120 to No PL. The mean initial BCVA (1.95, SD = 0.77 logMAR) improved to 1.45 logMAR, SD = 0.97 after treatment (P = 0.0435) but three patients had side effects of steroids. Initial visual acuity in Group 3 ranged from 20/40 to no PL. The mean initial BCVA (1.09 logMAR, SD = 1.10) worsened to 1.19 logMAR, SD = 1.06 after treatment after treatment (P = 0.0193). The improvement in BCVA when compared between the three groups was not significant.

CONCLUSION: Both erythropoietin and steroids are effective in the management of traumatic optic neuropathy. However, erythropoietin shows lesser or no side effects when compared to steroids.

PMID:36588242 | DOI:10.4103/ijo.IJO_945_22

Front Vet Sci. 2022 Dec 14;9:1056408. doi: 10.3389/fvets.2022.1056408. eCollection 2022.

ABSTRACT

Activation of one or both the Ras/MAPK and PI3K/Akt/mTOR signal transduction pathways are known to mediate oncogenicity of several canine and human cancers, including mucosal melanomas. Reciprocal cross activation between the two pathways can be a source of drug resistance. Consequently, oral dosing for plasma pharmacokinetic (PK) analysis and tolerability to a combination of sapanisertib, a dual TORC1/2 inhibitor, and trametinib, a MEK inhibitor, was evaluated in nontumor-bearing laboratory dogs for its potential application in parallel pathway targeting. Twelve dogs, divided into three equal cohorts, received either the combination or single agents. Animals were monitored for PK following single dose and 17-day repeat dosing, and by clinical observations, hematology, serum biochemistry, coagulation studies and urinalyses. A single trametinib dose (0.025 mg/kg), sulfated as dimethyl sulfoxide which enhanced its absorption, reached mean maximum concentration (Cmax) 0.64 ng/mL [18% coefficient of variation (CV)] at a median time to maximum concentration (Tmax) of 1.5 h (hr), and mean area under the concentration-time curve (AUC) 16.8 hr*ng/mL (14%CV), which were similar when given alone or in combination with sapanisertib. A prolonged half-life afforded 3-4-fold plasma accumulation of trametinib with daily dosing, analogous to humans. Trametinib PK mirrored previous regulatory data in dogs, while exposure approximated some published human values but generally not all patients. Sapanisertib-alone in canine plasma following single 0.1 mg/kg dose [mean Cmax 26.3 ng/mL (21%CV), median Tmax 2.0 hr, and mean AUC 248 hr*ng/mL (41%CV)] resembled levels in human therapeutic trials; whereas canine sapanisertib exposure was reduced when combined with trametinib, a known cytochrome P450 CYP3A4 inducer. Sex differences were not observed for either drug. Side effects upon repeat dosing with either or both drugs may include body weight loss, maldigestion, and cutaneous discoloration. The combination was tolerated without dose limiting toxicity, although clinical laboratory analyses revealed drug-induced acute-phase inflammation, proteinuria, and decreased blood reticulocytes, mild changes not necessitating intervention. Short-term results in dogs with this combination would appear to hold translational promise for clinical trial evaluation to target canine and possibly human melanoma, as well as other cancers having one or both signal transduction pathway activations.

PMID:36590793 | PMC:PMC9794608 | DOI:10.3389/fvets.2022.1056408

Front Pharmacol. 2022 Dec 15;13:1039867. doi: 10.3389/fphar.2022.1039867. eCollection 2022.

ABSTRACT

Triazole antifungal drugs (TAD) are widely used to treat invasive fungal infections due to their broad antifungal spectrum and low toxicity. Despite their preference in the clinic, multiple Adverse Events (AE) are still reported each year.

OBJECTIVE: We aimed to characterize the distribution of Adverse Events associated with Triazole antifungal drugs in different systems and to identify Important Medical Events (IME) signals for Triazole antifungal drugs.

METHODS: The U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) was queried for Adverse Events related to Triazole antifungal drugs from 2012 to 2022. The Adverse Events caused by all other drugs and non-TAD antifungal drugs were analyzed as references. Reporting odds ratio and Bayesian confidence propagation neural network of information components were used to evaluate the association between Triazole antifungal drugs and Important Medical Events. Visual signal spectrum is mapped to identify potential adverse reaction signals.

RESULTS: Overall, 10,262 Adverse Events were reported to be associated with Triazole antifungal drugs, of which 5,563 cases were defined as Important Medical Events. Common adverse drug reactions (ADR) mentioned in the instructions such as delirium and hypokalemia were detected, as well as unlabeled ADRs such as rhabdomyolysis and hepatitis fulminant. Cholestasis, drug-induced liver injury, QT interval prolongation and renal impairment have notable signals in all Triazole antifungal drugs, with 50 percent of patients developing a severe clinical outcome. Isavuconazole had the lowest signal intensity and demonstrated a superior safety profile.

CONCLUSION: Most results are generally consistent with previous studies and are documented in the prescribing instructions, but some IMEs are not included, such as hepatitis fulminant. Additional pharmaco-epidemiological or experimental studies are required to validate the small number of unlabeled ADRs. TAD-related Important Medical Eventshave a considerable potential to cause clinically serious outcomes. Clinical use of Triazole antifungal drugs requires more attention.

PMID:36588707 | PMC:PMC9798094 | DOI:10.3389/fphar.2022.1039867

Lipids Health Dis. 2022 Dec 31;21(1):150. doi: 10.1186/s12944-022-01766-z.

ABSTRACT

BACKGROUND: Cholesterol is crucial for tumor immune microenvironment (TIME) remodeling. Serum lipoprotein cholesterol is closely associated with gastric cancer (GC) progression, but whether it affects TIME remodeling is unknown.

METHODS: GC patients with differential serum high-density lipoprotein (HDL) or low-density lipoprotein (LDL) cholesterol levels were collected. After balancing the baseline, immunohistochemical staining was performed on serial whole-tissue sections to detect B-cell and T-cell subsets, macrophages, and PD-L1. Features of tertiary lymphoid structures (TLSs) and the extra-TLS zone, including TLS distribution and maturation, immune cell density, and PD-L1 expression, were measured by annotating TLSs or regions of interest (ROIs) in the extra-TLS zone.

RESULTS: A total of 9,192 TLSs and over 300 ROIs from 61 patients were measured. Compared to HDL-normal patients, HDL-low patients had a decreased secondary-TLS fraction or density but an elevated NK-cell density in the extra-TLS zone. Compared to LDL-normal patients, LDL-low patients had a higher ratio of PD-1 + T follicular helper cells to CD20 + B cells in TLSs, a higher ratio of PD-1 + T cells to CD8 + T cells and increased PD-1 + T-cell density in the extra-TLS zone. Different correlations were found in groups with differential HDL or LDL levels. Cell dynamics in the immune response were weaker in patients with low lipoprotein cholesterol. TLS parameters reached their peak earlier than those of the extra-TLS zone along with tumor progression.

CONCLUSION: Low serum lipoprotein cholesterol caused adverse effects on antitumor immunity in GC. Lipid management or immunometabolic drugs deserve more attention.

PMID:36585674 | PMC:PMC9805280 | DOI:10.1186/s12944-022-01766-z

J Clin Psychopharmacol. 2023 Jan-Feb 01;43(1):81-83. doi: 10.1097/JCP.0000000000001647.

NO ABSTRACT

PMID:36584260 | DOI:10.1097/JCP.0000000000001647

J Cardiovasc Med (Hagerstown). 2023 Feb 1;24(2):154-158. doi: 10.2459/JCM.0000000000001419. Epub 2022 Dec 22.

NO ABSTRACT

PMID:36583987 | DOI:10.2459/JCM.0000000000001419

Eur J Hosp Pharm. 2022 Dec 30:ejhpharm-2022-003454. doi: 10.1136/ejhpharm-2022-003454. Online ahead of print.

ABSTRACT

BACKGROUND: There is a high prevalence of multimorbidity and polypharmacy among older people, especially in people living with HIV (PLWH) with an increased life expectancy due to effective antiretroviral therapy (ART). Consequently, there is a higher risk of potentially inappropriate medications (PIM), potential drug-drug interactions (DI), and problems of non-adherence to treatment (NAC) in older PLWH. PIMDINAC criteria (potentially inappropriate medications (PIM), drug-drug interactions (DI), and non-adherence to treatment (NAC)) purport to jointly analyse these problems. The purpose of the study was to compare the prevalence of PIMDINAC criteria among elderly PLWH and non-infected patients with chronic diseases, and to determine whether HIV infection constitutes a predictor of the presence of PIMDINAC criteria, totally or partially.

METHODS: A cross sectional study was conducted between February and June 2020. HIV positive patients aged ≥65 years were compared with a group of patients with chronic conditions attending the outpatient hospital pharmacy service.

RESULTS: The study involved 140 patients: 47 HIV positive and 93 HIV negative, and mean age was 69 versus 73 years, respectively (p=0.062). The prevalence of total PIMDINAC criteria was similar between the groups (12.5 vs 10.8%, p=0.505). In relation to inappropriate medication, no differences were observed between groups (48.9 vs 55.9%, p=0434). Drug-drug interactions were higher in patients with chronic conditions (52.7 vs 25.5%, p=0.002) compared with non-adherence, which was higher in people with HIV (22.6 vs 65.6%, p<0.001). No differences in polypharmacy (≥6 and 11 drugs) rates were observed.

CONCLUSIONS: PIMDINAC criteria were highly prevalent in older PLWH, similar to non-infected patients. HIV infection in older people was associated with a lower risk of drug-drug interactions. However, non-adherence was a risk factor compared with age matched controls. Deprescribing strategies, including a capability-motivation-opportunity pharmaceutical care model based intervention should be implemented in clinical routines.

PMID:36585218 | DOI:10.1136/ejhpharm-2022-003454

Infect Dis Ther. 2022 Dec 30. doi: 10.1007/s40121-022-00746-1. Online ahead of print.

ABSTRACT

Cytomegalovirus (CMV) infection can have both direct and indirect effects after solid-organ transplantation, with a significant impact on transplant outcomes. Prevention strategies decrease the risk of CMV disease, although CMV still occurs in up to 50% of high-risk patients. Ganciclovir (GCV) and valganciclovir (VGCV) are the main drugs currently used for preventing and treating CMV. Emerging data suggest that letermovir is as effective as VGCV with fewer hematological side effects. Refractory and resistant CMV also still occur in solid-organ-transplant patients. Maribavir has been shown to be effective and have less toxicity in the treatment of refractory and resistant CMV. In this review paper, we discuss prevention strategies, refractory and resistant CMV, and drug-related side effects and their impact, as well as optimal use of novel anti-CMV therapies.

PMID:36583845 | DOI:10.1007/s40121-022-00746-1

Cureus. 2022 Nov 27;14(11):e31949. doi: 10.7759/cureus.31949. eCollection 2022 Nov.

ABSTRACT

Anaphylaxis is a sudden onset of systemic hypersensitivity caused by mast cell and basophil degranulation. Food, Hymenoptera venom, and drug allergy are among the leading causes of anaphylaxis, particularly in adults. We can consider anaphylaxis caused by swallowing food or medication as a form of poisoning. Because in anaphylaxis, just like in poisoning, an allergen entering the body poses a life-threatening risk. Therefore, the allergen should be removed from the digestive system immediately. However, the decontamination of the gastrointestinal tract is not routinely used to prevent further absorption of allergens from the intestine into the systemic circulation. Among the gastrointestinal decontamination methods is the use of activated charcoal. In this article, we present four patients who developed anaphylaxis due to drug and food intake and were administered oral activated charcoal after their primary treatment (on average, 15-45 minutes after the first presentation) was completed. The youngest of the patients was 22 years old, and the oldest was 40. No side effects, prolonged anaphylactic state, and biphasic reactions were observed in the follow-up of the patients. All patients were discharged after 48-72 hours of hospitalization. The routine approach to poisoning treatment includes patient stabilization, toxidrome recognition, antidote administration, and supportive care, as well as measures to enhance toxin elimination. In anaphylaxis caused by oral allergens, the substance that initiates the reaction can be compared to a kind of toxin. Eliminating the allergen and reducing its absorption could be achieved by administering activated charcoal. Activated charcoal should be considered adjunctive therapy in treating food and oral drug-induced anaphylaxis. This treatment, when administered in a timely manner, might prevent the development of biphasic reactions and the prolongation of the allergic process in anaphylaxis.

PMID:36582570 | PMC:PMC9794912 | DOI:10.7759/cureus.31949

BMJ Open. 2022 Sep 1;12(9):e060967. doi: 10.1136/bmjopen-2022-060967.

ABSTRACT

INTRODUCTION: Esketamine is the S-enantiomer of racemic ketamine and has been approved by the Food and Drug Administration for the management of treatment resistant depression, demonstrating effective and long-lasting benefits. The objective of this observational study is to elucidate the association of intranasal (IN) esketamine with beneficial and negative outcomes in the management of treatment resistant major depressive disorder.

METHODS AND ANALYSIS: This is a multicentre prospective cohort observational study of naturalistic clinical practice. We expect to recruit 10 patients per research centre (6 centres, total 60 subjects). After approval to receive IN esketamine as part of their standard of care management of moderate to severe treatment resistant depression, patients will be invited to participate in this study. Association of esketamine treatment with outcomes in the management of depression will be assessed by measuring the severity of depression symptoms using the Montgomery-Åsberg Depression Rating Scale (MADRS), and tolerability by systematically tracking common side effects of ketamine treatment, dissociation using the simplified 6-Item Clinician Administered Dissociative Symptom Scale and potential for abuse using the Likeability and Craving Questionnaire (LCQ). Change in depressive symptoms (MADRS total scores) over time will be evaluated by within-subject repeated measures analysis of variance. We will calculate the relative risk associated with the beneficial (reduction in total scores for depression) outcomes, and the side effect and dropout rates (tolerability) of adding IN esketamine to patients' current pharmacological treatments. Covariate analysis will assess the impact of site and demographic variables on treatment outcomes.

ETHICS AND DISSEMINATION: Approval to perform this study was obtained through the Health Sciences Research Ethics Board at Queen's University. Findings will be shared among collaborators, through departmental meetings, presented on different academic venues and publishing our manuscript.

PMID:36581972 | PMC:PMC9438206 | DOI:10.1136/bmjopen-2022-060967

BMC Med. 2022 Dec 30;20(1):493. doi: 10.1186/s12916-022-02696-4.

ABSTRACT

BACKGROUND: This trial aimed to analyse the safety, effectiveness and transcriptomic characteristics of neoadjuvant toripalimab plus chemotherapy in II-III non-small-cell lung cancer (NSCLC).

METHODS: Patient eligibility mainly involved treatment-naive, clinical stage II-III and wild-type EGFR/ALK NSCLC. The patients received 2-4 cycles of toripalimab (240 mg q3w) plus carboplatin-based chemotherapy. After the second treatment cycle, all patients were re-evaluated by a multidisciplinary team. Candidates eligible for surgery underwent surgery; otherwise, patients received the remaining treatment cycles. The primary endpoints were safety and major pathological response (MPR). Secondary endpoints were R0 resection rate, progression-free survival (PFS) and overall survival (OS). RNA sequencing of baseline and post-treatment samples was conducted to explore the transcriptomic characteristics of the therapeutic response.

RESULTS: In total, 50 eligible patients were enrolled, including 12 (24.0%) with resectable disease (RD) and 38 (76.0%) with potentially resectable disease (PRD). Treatment-related adverse events (TRAEs) were recorded in 48 cases (96.0%). Severe TRAEs occurred in 3 (6.0%) cases, including myelosuppression, drug-induced liver injury and death related to haemoptysis. The objective response rate (ORR) was 76.0%, with 8 (16.0%) patients having a complete response (CR), 30 (60.0%) partial response (PR), 10 (20.0%) stable disease (SD) and 2 (4.0%) progressive disease (PD). Surgery could be achieved in 12 (100%) patients with RD and 25 (65.8%) with PRD; 1 (2.0%) with PRD refused surgery. Therefore, R0 resection was performed for all 36 (100%) patients who underwent surgery; 20 (55.6%) achieved MPR, including 10 (27.8%) with a complete pathological response (pCR). The CHI3L1 (chitinase-3-like protein 1) immunohistochemistry (IHC) expression of baseline tumour samples could predict the therapeutic response (AUC=0.732), OS (P=0.017) and PFS (P=0.001). Increased PD-1 expression, T cell abundance and immune-related pathway enrichment were observed in post-treatment samples compared to baseline in the response group (CR+PR) but not in the non-response group (SD+PD).

CONCLUSIONS: Neoadjuvant toripalimab plus chemotherapy was safe and effective, with a high MPR and manageable TRAEs for II-III NSCLC, even converting initially PRD to RD. Disparate transcriptomic characteristics of therapeutic efficiency were observed, and CHI3L1 expression predicted therapeutic response and survival.

TRIAL REGISTRATION: ChiCTR1900024014, June 22, 2019.

PMID:36581917 | DOI:10.1186/s12916-022-02696-4

JAMA Netw Open. 2022 Dec 1;5(12):e2248803. doi: 10.1001/jamanetworkopen.2022.48803.

ABSTRACT

IMPORTANCE: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Hepatotoxic effects, including hyperbilirubinemia and elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, are common during all phases of therapy and are linked to several chemotherapeutic agents, including asparaginase, mercaptopurine, and methotrexate.

OBJECTIVE: To determine which genetic variants were associated with hyperbilirubinemia and elevated ALT and AST levels in children, adolescents, and young adults treated for ALL.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective analysis of a multiethnic genome-wide association study was conducted between January 1, 2019, and April 15, 2022, including patients treated as part of Children's Oncology Group (COG) trials with centers in the United States, Canada, and Australia, which accrued data from December 29, 2003, to January 21, 2011 (AALL0232), and from January 22, 2007, to July 24, 2014 (AALL0434). Germline genotypes were interrogated using genome-wide arrays and imputed using a National Institutes of Health TOPMed Imputation server. Mixed-effects logistic regressions were used to account for multiple episodes for an individual patient. Genotype × treatment phase interaction was tested to uncover phase-specific genetic risk factors.

EXPOSURES: Total duration of multiagent protocol chemotherapy ranging from 2.5 to 3.5 years.

MAIN OUTCOMES AND MEASURES: The primary outcomes were National Cancer Institute Common Terminology Criteria for Adverse Events (version 4) hyperbilirubinemia of grade 3 or higher and elevated liver ALT and AST levels.

RESULTS: A total of 3557 participants were included in the analysis (2179 [61.3%] male; median age, 11.1 [range, 1-30] years). Among 576 known variants associated with these liver function test results in the general population, UGT1A1 variant rs887829 and PNPLA3 variant rs738409 were associated with increased risk of hyperbilirubinemia (odds ratio [OR], 2.18 [95% CI, 1.89-2.53]; P = 6.7 × 10-27) and ALT and AST levels (OR, 1.27 [95% CI, 1.15-1.40]; P = 3.7 × 10-7), respectively, during treatment for ALL. Corresponding polygenic risk scores were associated with hepatotoxic effects across all therapy phases and were largely driven by UGT1A1 and PNPLA3 variants. Genome-wide association analysis revealed an age-specific variant near the CPT1A gene that was only associated with elevated ALT and AST levels among patients younger than 10 years (OR, 1.28 [95% CI, 1.18-1.39]; P = 8.7 × 10-10).

CONCLUSIONS AND RELEVANCE: These results suggest a strong genetic basis for interpatient variability in hyperbilirubinemia and aminotransferase level elevations during leukemia chemotherapy.

PMID:36580335 | DOI:10.1001/jamanetworkopen.2022.48803

Tzu Chi Med J. 2022 Oct 3;34(4):409-417. doi: 10.4103/tcmj.tcmj_74_22. eCollection 2022 Oct-Dec.

ABSTRACT

Phenytoin (PHT) was first synthesized as a barbiturate derivative and was approved in 1953 by the Food and Drug Administration. This work aimed to review the pathophysiology, epidemiology, clinical presentation, and treatment of PHT-associated movement disorders (MDs). Studies were searched in relevant databases (ScienceDirect, Google Scholar, Excerpta Medica, Latin American and Caribbean Health Sciences Literature, Medline, and Scientific Electronic Library Online) and were selected by two reviewers irrespective of language between 1963 and 2021. Papers of PHT-induced ataxia alone or tremor were excluded. In total, 127 reports with 219 individuals who developed MDs associated with PHT were encountered. MDs found: 126 dyskinesias, 49 myoclonus, 19 dystonia, 14 parkinsonism, 6 tics, 3 stuttering, and 2 restless legs syndrome. The mean age was 35 years (standard deviation [SD]: 23.5) and the predominant sex was male (53.4%). The mean PHT dose when the MD took place was 370.4 mg (SD: 117.5). A serum PHT concentration was reported in 103 cases, ranging from 4 to 110 μg/mL (median: 27.7 μg/mL). No significant relationship was found between PHT dose and age or PHT level. The mean onset time of PHT-associated MD was 23.4 months (SD: 4.4). The mean recovery time after MD management was 3.7 weeks (SD: 1.1). Regarding management, the most common form was PHT withdrawal in 90.4%. 86.3% of the individuals recovered fully. PHT-induced MD was extensively reported in the literature. Only general terms were used in the majority of the reports. The mechanisms underlying the adverse events caused by PHT probably depend on the presence of predisposing factors.

PMID:36578637 | PMC:PMC9791846 | DOI:10.4103/tcmj.tcmj_74_22

Sante Publique. 2022;34(4):461-469. doi: 10.3917/spub.224.0461.

ABSTRACT

Introduction&#160;: Traveling regularly to malaria endemic areas increasingly exposes travelers to various risks which could be mitigated by a pre-travel health consultation. The objective was to study the impact of advice provided during a pre-travel consultation on travelers&#8217; behaviors and practices to identify travelers&#8217; profiles and adapt the prevention recommendations before trave-ling to intertropical zones.Methods&#160;: Two self-assessment questionnaires (Q1-before and Q2-after travelling) were proposed to 271 individuals over 5 months of traveler consultations to assess behaviors (Q1) and practices (Q2). Questionnaires gathered travelers&#8217; profiles, source of information, travel diet and lifestyle, personal vector control, malaria chemoprophylaxis and other frequent risks.Results&#160;: Diet recommendations were the least followed (16&#160;%), especially for people&lt;55 (p&lt;0.03) as well as Visiting Friends and Relatives (VFR) (p&lt;0,001). A correlation between behaviors and practices for personal vector control and immunization and malaria chemoprophylaxis were found (resp.&#160;89% and 78%). Mosquito nets and long sleeve clothes were underused. Changes of opinion resulting from concerns of potential side effects and lack of efficiency (&lt;7%) explained the non-compliance to the pre-travel recommendations. During the stay, although 24% of travelers got sick, medical consultations (&lt;5%) and hospital admissions (&lt;1%) remained low. The General Practitioner remains the main point of contact (41%).Discussion&#160;: Better identifying travelers&#8217; characteristics would allow to improve travel consultation, to refer to their knowledge and focus on preventive measures. It is crucial to highlight the importance of diet measures and insist on the low likelihood of adverse effects in Malaria Chemoprophylaxis.

PMID:36577674 | DOI:10.3917/spub.224.0461

Int J Hematol. 2022 Dec 28. doi: 10.1007/s12185-022-03514-6. Online ahead of print.

ABSTRACT

Tirabrutinib is a Bruton's tyrosine kinase inhibitor for treating B-cell malignancies. We report the final results of a Phase I study of tirabrutinib in 17 Japanese patients with B-cell malignancies. Patients were administered tirabrutinib at a dose of 160 mg, 320 mg, or 480 mg once daily, or 300 mg twice daily (N = 3, 3, 4, and 7, respectively). Three patients continued tirabrutinib until study completion (November 30, 2020). Adverse events (AEs) occurred in all 17 patients, with Grade 3-4 AEs in 8 (47.1%), serious AEs in 7 (41.2%), drug-related AEs in 16 (94.1%), and Grade 3-4 drug-related AEs in 6 (35.3%). Drug-related AEs reported in 3 or more patients were rash, vomiting, neutropenia, arthralgia, and malaise. One additional serious AE (benign neoplasm of the lung, unrelated to tirabrutinib) occurred after the previous data cutoff (January 4, 2018). Tirabrutinib administration and response assessment were continued for over 4 years in 4 patients. The overall response rate was 76.5% (13/17 patients). The median (range) time to response and duration of response were 0.9 (0.9-5.9) months and 2.59 (0.08-5.45) years, respectively. These findings demonstrate the long-term safety and efficacy of tirabrutinib in Japanese patients with B-cell malignancies.Clinical trial registration: JapicCTI-142682 ( http://www.clinicaltrials.jp/ ).

PMID:36576659 | DOI:10.1007/s12185-022-03514-6

Support Care Cancer. 2022 Dec 27;31(1):86. doi: 10.1007/s00520-022-07464-x.

ABSTRACT

PURPOSE: After breast cancer treatment, women with breast cancer may experience distress caused by treatment side effects, both in physical and psychological aspects. Technology use is increasing in favor among women. Therefore, it is essential to update the scientific evidence regarding mobile and web apps' effectiveness in managing the side effects of breast cancer treatments for breast cancer survivors. The purpose of this systematic review was to investigate the scientific evidence on the effectiveness of mobile and web apps in managing the side effects of breast cancer treatments among this group.

METHODS: A literature search was conducted using ScienceDirect, Scopus, PubMed, CINAHL, and Cochrane. Published papers in English focused on mobile and web apps and the side effects of breast cancer treatment in breast cancer survivors were selected. The search reviewed studies from January 2011 to December 2021. From a total of 925 retrieved manuscripts, 11 studies were included for analysis.

RESULTS: The findings showed that mobile apps were more frequently used and more likely to be an effective method for managing the side effects of breast cancer treatment among breast cancer survivors. The content in web or mobile apps for breast cancer survivors should include five categories: (1) information about cancer, (2) overview of cancer care, (3) opportunities for interaction with other people, (4) symptom management strategies, and (5) feedback about cancer treatment side effect management. However, a few studies examined the effects of a combination of mobile and web apps in managing breast cancer treatment side effects. Therefore, future research is needed to examine solo and combination use. In addition, more rigorous studies are warranted to examine these interventions.

CONCLUSIONS: Nurses may refer survivors to these resources to obtain more information and effectively manage the signs and symptoms of breast cancer and its treatment side effects.

PMID:36574048 | DOI:10.1007/s00520-022-07464-x

Int J Immunopathol Pharmacol. 2022 Jan-Dec;36:3946320221148999. doi: 10.1177/03946320221148999.

ABSTRACT

Background: An adverse effect of COVID-19 vaccine is possible and it is necessary to monitor it. Methods and results: This is a correspondence on the published article on multiple sites of thrombosis without thrombocytopenia and COVID-19 vaccine. Conclusion: Confounding factors regarding thrombosis without thrombocytopenia and COVID-19 vaccine are discussed.

PMID:36572989 | DOI:10.1177/03946320221148999

Animal Model Exp Med. 2022 Dec 27. doi: 10.1002/ame2.12301. Online ahead of print.

ABSTRACT

BACKGROUND: Knowing the variability of blood coagulation responses to liver damage of different origins can provide a key to curing liver tissues or to mitigating treatment side effects. The aim of the present work was to compare the changes in the main components of hemostasis under experimental drug-induced hepatosis and hepatitis in rats.

METHODS: We modeled diclofenac-induced hepatitis and tetracycline-induced hepatosis. Hemostasis response was gauged by measuring fibrinogen, factor X, protein C (PC), and prothrombin in plasma. The decarboxylated form of prothrombin was detected by measuring prothrombin index and ecamulin index. Platelet reactivity was studied using aggregometry.

RESULTS: Both hepatitis and hepatosis decreased the synthesis of fibrinogen, factor X, and prothrombin. However, protein carboxylation was not disrupted in hepatosis but was much impaired in hepatitis. PC decreased in both models as a consequence of its consumption possibly during inflammatory response. Platelet aggregation rate was lower in hepatosis but higher in hepatitis.

CONCLUSIONS: Our findings imply the need for a thorough monitoring of the hemostasis system in liver diseases to avoid possible thrombotic complications. Its state indicates the disorder's rate and character.

PMID:36574273 | DOI:10.1002/ame2.12301

Gac Med Mex. 2022;158(5):257-258. doi: 10.24875/GMM.M22000692.

NO ABSTRACT

PMID:36572037 | DOI:10.24875/GMM.M22000692

Int Urol Nephrol. 2022 Dec 26. doi: 10.1007/s11255-022-03432-w. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the effect of finerenone on cardiovascular events in Kidney Disease and/or Diabetes.

METHODS: The ClinicalTrials.gov, Medline, EMBASE, Web of Science, Cochrane Library databases were systematically searched from the inception dates to December 20, 2021 in order to identify randomized controlled trials that evaluated the effect of finerenone on cardiovascular events in Kidney Disease and/or Diabetes, without language restriction. This meta-analysis collected data from 7 randomized clinical trials that evaluated the effect of finrrenone in 15,618 patients with kidney disease and/or diabetes. Risk of bias was assessed by Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed by I2 statistic. The main endpoints included death from cardiovascular causes, death from any cause, incidence of myocardial infarction, rate of heart failure, hospitalization for any cause, rate of total advent events and study-drug-related adverse events.

RESULTS: A total of 7 randomized controlled trials involving 15,618 fulfilled the inclusion criteria. The outcomes of this meta-analysis presented that finerenone significantly reduced the death from any cause (95% CI 0.82-0.99; P = 0.031), risk of heart failure (95% CI 0.67-0.92; P = 0.002) among patients with kidney disease and/or diabetes when compared to control group. Besides, finerenone could not reduce the incidence of death from cardiovascular, myocardial infarction and hospitalization for any cause among patients with kidney disease and/or diabetes (p > 0.05). In terms of safety, finerenone shared the same risk of total advent events with placebo among patients with kidney disease and/or diabetes (p > 0.05). However, finerenone had higher risk of study-drug-related advent events than placebo among patients with kidney disease and/or diabetes (95% CI 1.27-1.48; P < 0.001).

CONCLUSIONS: In patients with kidney disease and/or diabetes, treatment with finerenone resulted in lower risk of death from any cause and heart failure than placebo. However, the study-drug-related advent events also increased significantly at the same time.

PMID:36571667 | DOI:10.1007/s11255-022-03432-w