Australas J Dermatol. 2023 Sep 19. doi: 10.1111/ajd.14162. Online ahead of print.

NO ABSTRACT

PMID:37724715 | DOI:10.1111/ajd.14162

Cancer Med. 2023 Sep 18. doi: 10.1002/cam4.6556. Online ahead of print.

ABSTRACT

OBJECTIVE: Drug-induced side effects, particularly serious adverse events (SAEs), often affect cancer patients enrolled in clinical trials. However, little is known about anxiety and depression in cancer patients who experienced SAEs. This study evaluated the prevalence of anxiety and depression in cancer patients enrolled in clinical trials who experienced SAEs and explored the risk factors.

METHODS: A multi-center, cross-sectional survey was conducted in hospitals affiliated with the University of Science and Technology of China from December 2021 to November 2022. A total of 112 cancer patients who experienced SAEs while enrolled in clinical trials, and who completed the informed consent process and study questionnaires, were included in the final analysis.

RESULTS: The rate of moderate-severe depression in cancer patients was 38.4% and that of moderate-severe anxiety was 13.4%. Among the patients who had moderate-severe anxiety, 93.3% had concurrent moderate-severe depression. Lower cognitive function and lower global quality of life were risk factors for depression in cancer patients who experienced SAEs. Pain, low emotional function, low global quality of life, and a high Impact of Events Scale score were risk factors for anxiety.

CONCLUSIONS: Cancer patients enrolled in a clinical trial who experienced SAEs tended to be anxious and depressed, particularly the latter. These results indicate the need to evaluate anxiety and depression, and mental health treatment among cancer patients with SAEs in clinical trials.

PMID:37723836 | DOI:10.1002/cam4.6556

BMC Complement Med Ther. 2023 Sep 18;23(1):328. doi: 10.1186/s12906-023-04154-x.

ABSTRACT

BACKGROUND: Migraine is a complex neurovascular disorder with considerable clinical, social and economic issues. Tai chi has the potential to be an alternative prophylactic treatment for migraine with high safety since the adverse effects and limited efficacy of available medications.

AIMS: The proposed study aims to compare the prophylaxis efficacy of 24-week Tai Chi training on migraine attacks with the standard prophylactic medication; and to explore the mechanism of Tai Chi in preventing migraine attacks by analyzing the associations between changes of migraine attacks and changes of neurovascular functions and inflammatory makers.

METHOD: This is a two-arm parallel non-inferiority randomized controlled trial. In total 220 Hong Kong Chinese women aged 18-65 years with diagnosis of episodic migraine will be recruited and randomized to either the Tai Chi training group or the standard prophylactic medication group with 1:1 ratio, and receive the 24 weeks of modified 33-short form Yang-style Tai Chi training and the standard prophylactic medications, respectively. A 24-week follow-up will be implemented for both groups. For efficacy examination, the primary outcome was the frequency of migraine attacks measured by the migraine diary; and for the mechanism exploration, the primary outcome was the volume and number of white matter hyperintensity (WMH) measured by magnetic resonance imaging (MRI). The measurements will be conducted at the baseline, 24th weeks, and 48th weeks. Linear mixed model will be adopted to comprehensively analyze the changes of variables within and between groups.

DISCUSSION: Given the importance of reducing disease burden and financial cost of migraine attacks, the findings of this study will provide new insights regarding the role of Tai Chi in alleviating migraine burden and further shed light on the mechanism action of Tai Chi on preventing headache attacks.

TRIAL REGISTRATION: ClinicalTrials.gov NCT05690737. Registered on January 28, 2023.

PMID:37723467 | PMC:PMC10507971 | DOI:10.1186/s12906-023-04154-x

BMC Infect Dis. 2023 Sep 18;23(1):612. doi: 10.1186/s12879-023-08558-5.

ABSTRACT

BACKGROUND: Public health depends largely on people's knowledge, beliefs, or behaviors regarding their health and medical treatments. Although works based on the health belief model have shown that public beliefs about medical treatments affect willingness to take the treatments, little is known about the effects of changes in beliefs on attitudes toward treatment. How one's past experiences relate to one's beliefs about a given medical treatment is worth considering.

METHODS: We implemented an online panel survey in February 2021 and March 2022 in Japan before and after COVID-19 vaccines were administered to the public within the country. We exploited delayed localized hypersensitivity reactions to COVID-19 vaccines, namely, "COVID arm", as an exogenous shock to investigate the relationship between past negative experiences and current beliefs about medical treatments or science. "COVID arm" was an unexpected side effect and thus likely caused updated beliefs about the vaccine. Out of the nonprobability sample of 15,000 respondents in the first wave in February 2021, 9,668 respondents also responded to the second wave conducted in March 2022. Outcome variables were whether experiencing "COVID arm" affected the respondents' 1) confidence in vaccine safety, 2) willingness to take the next dose of COVID-19 vaccines, 3) acknowledgment of the importance of vaccination, and 4) confidence in science. We measured the impact of experience with "COVID arm" on changes in the probability that survey respondents would respond affirmatively to questions posed about the issues listed above.

RESULTS: Experiencing "COVID arm" significantly lowered confidence in the safety of vaccination by 4.3 percentage points, which was approximately 6% of the sample mean for the first wave, and lowered the probability of taking a second dose of the COVID-19 vaccine by 1.5 percentage points. These adverse impacts were observed after conditioning background characteristics and prior confidence in vaccination. Experiencing "COVID arm" affected neither the acknowledged importance of vaccination nor confidence in science in a statistically significant way.

CONCLUSIONS: An unexpected and uncomfortable shock regarding beliefs about a treatment decreases willingness to take the treatment. An appropriate public health policy should account for this effect.

TRIAL REGISTRATION: The survey was preregistered with the American Economic Association's RCT Registry (Fukai et al., 2022).

PMID:37723413 | PMC:PMC10507958 | DOI:10.1186/s12879-023-08558-5

Nat Commun. 2023 Sep 18;14(1):5774. doi: 10.1038/s41467-023-41552-8.

ABSTRACT

The organic anion transporting polypeptides OATP1B1 and OATP1B3 are membrane proteins that mediate uptake of drugs into the liver for subsequent conjugation and biliary excretion, a key step in drug elimination from the human body. Polymorphic variants of these transporters can cause reduced drug clearance and adverse drug effects such as statin-induced rhabdomyolysis, and co-administration of OATP substrates can lead to damaging drug-drug interaction. Despite their clinical relevance in drug disposition and pharmacokinetics, the structure and mechanism of OATPs are unknown. Here we present cryo-EM structures of human OATP1B1 and OATP1B3 bound to synthetic Fab fragments and in functionally distinct states. A single estrone-3-sulfate molecule is bound in a pocket located in the C-terminal half of OATP1B1. The shape and chemical nature of the pocket rationalize the preference for diverse organic anions and allow in silico docking of statins. The structure of OATP1B3 is determined in a drug-free state but reveals a bicarbonate molecule bound to the conserved signature motif and a histidine residue that is prevalent in OATPs exhibiting pH-dependent activity.

PMID:37723174 | PMC:PMC10507018 | DOI:10.1038/s41467-023-41552-8

Appl Nurs Res. 2023 Oct;73:151717. doi: 10.1016/j.apnr.2023.151717. Epub 2023 Jul 30.

ABSTRACT

There is ongoing concern about vaccine hesitancy amongst young adults in Turkey. In October 2021 just 53% of 18-25-year olds were fully vaccinated. This study aimed to assess the knowledge and attitudes of university students concerning adult immunization, COVID-19 vaccine, and COVID-19 vaccine literacy to better understand why it is difficult to encourage young adults to be vaccinated. This cross-sectional study was conducted with 307 university students that included socio-demographic characteristics, knowledge of adult immunization, attitudes toward COVID-19 vaccination, and vaccine literacy. The data were collected using a socio-demographic characteristics form, a knowledge form for adult immunization, the attitudes toward the COVID-19 vaccine scale, and the COVID-19 vaccine literacy scale. While more than half of the students (52.8%) had a low level of knowledge about adult immunization, half percent of the students (50.5%) stated that they did not know anything about adult vaccination. Twenty-six and half percent of the students stated that they weren't vaccinated because they were afraid of the side effects of the vaccines for adults. The difference between the student's level of knowledge about adult immunization and their mean scores on the attitudes toward the COVID-19 vaccine scale was not statistically significant (p > 0.05); whereas, the difference between their level of knowledge about adult immunization and their mean scores of the COVID-19 vaccine literacy scale was statistically significant (p < 0.05). There were low levels of vaccine literacy amongst Turkish university students and more than half of the students reported that they did not know and twenty-six percent of students (26 %) of the students were fearful of vaccine side effects. Students outside of the faculty of health had a low level of knowledge about vaccines. Examining and improving vaccine literacy amongst university students could lead to improved compliance with vaccination programs for both COVID-19 and other adult vaccines that are important for community health and well-being.

PMID:37722785 | DOI:10.1016/j.apnr.2023.151717

Appl Nurs Res. 2023 Oct;73:151734. doi: 10.1016/j.apnr.2023.151734. Epub 2023 Aug 18.

ABSTRACT

BACKGROUND: In the first 24 h after surgery, it is necessary to evaluate the patient responses to pain, analgesia and patient satisfaction to prevent complications related to the pain management process.

AIM: To evaluate patients' outcomes (pain qualities, side effects of the pain management, pain treatment satisfaction, non-pharmacological pain treatment methods, predictors of pain management satisfaction and percentage of pain relief) according to the Revised American Pain Society Patient Outcome Questionnaire (APS-POQ-R) in the first 24 h.

DESIGN: Cross-sectional study.

METHODS: The study sample was comprised of 700 patients, who were surgically treated at the surgical clinics of a university hospital and completed the first postoperative 24 h. The data was collected through the "Patient Information Form" and the "Turkish version of the revised American Pain Society Patient Outcome Questionnaire (APS-POQ-R)".

RESULTS: The medians of the lowest and the worst postoperative pain severity level were 3.0 and 7.0, respectively. Patients experienced severe pain in 60 % of the first postoperative 24 h and reported that 70 % of their pain eventually decreased. A positive and significant correlation was found between pain interference, pain-affected mood/emotions, the severity of pain-related side effects, the least and worst pain severity levels and severe pain, and the percentage of time experienced with severe pain.

CONCLUSIONS: Most of the patients experienced severe pain, which restricted their daily life activities and led to negative emotions. Acute postoperative pain may negatively affect patient outcomes and delay postoperative recovery during the early period. Therefore, pain should be managed in the early period to prevent physical and psychological side effects.

PMID:37722782 | DOI:10.1016/j.apnr.2023.151734

J Med Internet Res. 2023 Sep 18;25:e44656. doi: 10.2196/44656.

ABSTRACT

BACKGROUND: Mental health problems are recognized as a pressing public health issue, and an increasing number of individuals are turning to online communities for mental health to search for information and support. Although these virtual platforms have the potential to provide emotional support and access to anecdotal experiences, they can also present users with large amounts of potentially inaccurate information. Despite the importance of this issue, limited research has been conducted, especially on the differences that might emerge due to the type of content moderation of online communities: peer-led or expert-led.

OBJECTIVE: We aim to fill this gap by examining the prevalence, the communicative context, and the persistence of mental health misinformation on Facebook online communities for mental health, with a focus on understanding the mechanisms that enable effective correction of inaccurate information and differences between expert-led and peer-led groups.

METHODS: We conducted a content analysis of 1534 statements (from 144 threads) in 2 Italian-speaking Facebook groups.

RESULTS: The study found that an alarming number of comments (26.1%) contained medically inaccurate information. Furthermore, nearly 60% of the threads presented at least one misinformation statement without any correction attempt. Moderators were more likely to correct misinformation than members; however, they were not immune to posting content containing misinformation, which was an unexpected finding. Discussions about aspects of treatment (including side effects or treatment interruption) significantly increased the probability of encountering misinformation. Additionally, the study found that misinformation produced in the comments of a thread, rather than as the first post, had a lower probability of being corrected, particularly in peer-led communities.

CONCLUSIONS: The high prevalence of misinformation in online communities, particularly when left uncorrected, underscores the importance of conducting additional research to identify effective mechanisms to prevent its spread. This is especially important given the study's finding that misinformation tends to be more prevalent around specific "loci" of discussion that, once identified, can serve as a starting point to develop strategies for preventing and correcting misinformation within them.

PMID:37721800 | DOI:10.2196/44656

Cochrane Database Syst Rev. 2023 Sep 18;9(9):CD013673. doi: 10.1002/14651858.CD013673.pub2.

ABSTRACT

BACKGROUND: A detailed summary and meta-analysis of the dose-related effect of pravastatin on lipids is not available.

OBJECTIVES: Primary objective To assess the pharmacology of pravastatin by characterizing the dose-related effect and variability of the effect of pravastatin on the surrogate marker: low-density lipoprotein (LDL cholesterol). The effect of pravastatin on morbidity and mortality is not the objective of this systematic review. Secondary objectives • To assess the dose-related effect and variability of effect of pravastatin on the following surrogate markers: total cholesterol; high-density lipoprotein (HDL cholesterol); and triglycerides. • To assess the effect of pravastatin on withdrawals due to adverse effects.

SEARCH METHODS: The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials (RCTs) up to September 2021: CENTRAL (2021, Issue 8), Ovid MEDLINE, Ovid Embase, Bireme LILACS, the WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions.

SELECTION CRITERIA: Randomized placebo-controlled trials evaluating the dose response of different fixed doses of pravastatin on blood lipids over a duration of three to 12 weeks in participants of any age with and without evidence of cardiovascular disease.

DATA COLLECTION AND ANALYSIS: Two review authors independently assessed eligibility criteria for studies to be included, and extracted data. We entered lipid data from placebo-controlled trials into Review Manager 5 as continuous data and withdrawal due to adverse effects (WDAEs) data as dichotomous data. We searched for WDAEs information from all trials. We assessed all trials using Cochrane's risk of bias tool under the categories of sequence generation, allocation concealment, blinding, incomplete outcome data, selective reporting, and other potential biases.

MAIN RESULTS: Sixty-four RCTs evaluated the dose-related efficacy of pravastatin in 9771 participants. The participants were of any age, with and without evidence of cardiovascular disease, and pravastatin effects were studied within a treatment period of three to 12 weeks. Log dose-response data over the doses of 5 mg to 160 mg revealed strong linear dose-related effects on blood total cholesterol and LDL cholesterol, and a weak linear dose-related effect on blood triglycerides. There was no dose-related effect of pravastatin on blood HDL cholesterol. Pravastatin 10 mg/day to 80 mg/day reduced LDL cholesterol by 21.7% to 31.9%, total cholesterol by 16.1% to 23.3%,and triglycerides by 5.8% to 20.0%. The certainty of evidence for these effects was judged to be moderate to high. For every two-fold dose increase there was a 3.4% (95% confidence interval (CI) 2.2 to 4.6) decrease in blood LDL cholesterol. This represented a dose-response slope that was less than the other studied statins: atorvastatin, rosuvastatin, fluvastatin, pitavastatin and cerivastatin. From other systematic reviews we conducted on statins for its effect to reduce LDL cholesterol, pravastatin is similar to fluvastatin, but has a decreased effect compared to atorvastatin, rosuvastatin, pitavastatin and cerivastatin. The effect of pravastatin compared to placebo on WADES has a risk ratio (RR) of 0.81 (95% CI 0.63 to 1.03). The certainty of evidence was judged to be very low.

AUTHORS' CONCLUSIONS: Pravastatin lowers blood total cholesterol, LDL cholesterol and triglyceride in a dose-dependent linear fashion. This review did not provide a good estimate of the incidence of harms associated with pravastatin because of the lack of reporting of adverse effects in 48.4% of the randomized placebo-controlled trials.

PMID:37721222 | PMC:PMC10506175 | DOI:10.1002/14651858.CD013673.pub2

Clin Ther. 2023 Sep 16:S0149-2918(23)00312-0. doi: 10.1016/j.clinthera.2023.08.010. Online ahead of print.

ABSTRACT

PURPOSE: The therapy and management of Gaucher disease (GD) have radically changed with the use of substrate reduction therapy, of which eliglustat is the most widely known drug, allowing it to overcome the limits of enzyme replacement therapy (ERT). The rarity of GD and the limited use of eliglustat outside clinical trials require further study of its strengths and weaknesses.

METHODS: In this study, we evaluated the effectiveness and safety of eliglustat in a cohort of 12 patients with GD followed up in our center, reporting a reduction in both chitotriosidase (394.3 vs 181.1 nmol/h/mL, P = 0.027) and glucosylsphingosine values (45.1 vs 18.9 ng/mL, P <0.001) after at least 12 months of therapy compared with baseline, regardless of patient demographic characteristics and GD characteristics.

FINDINGS: There were no drug-related serious adverse effects and no drug-related cardiac events. Most adverse events were mild and transient, mainly dyspepsia and abdominal pain. Of interest, we reported an absence of statistical difference in terms of response regarding glucosylsphingosine reduction in relation to naive or prior exposure to ERT (P = 0.296), which was confirmed also when patients were placed in naive and treated groups for <5 vs >5 years (P = 0.667).

IMPLICATIONS: The use of eliglustat immediately after diagnosis may guarantee the best treatment for patients with milder phenotypes or with aggressive disease after an initial stabilization with ERT compared with ERT, which cannot adequately remove the disease burden despite the apparent response, thus potentially reducing future complications caused by substrate deposits.

PMID:37722956 | DOI:10.1016/j.clinthera.2023.08.010

Ther Adv Med Oncol. 2023 Sep 13;15:17588359231198453. doi: 10.1177/17588359231198453. eCollection 2023.

ABSTRACT

BACKGROUND: Immune checkpoint inhibitors (ICIs) have shown remarkable therapeutic outcomes among cancer patients. Durvalumab plus tremelimumab (DT) is under investigation as a new ICI combination therapy, and its efficacy has been reported in various types of cancer. However, the safety profile of DT remains unclear, especially considering rare adverse events (AEs).

OBJECTIVE: We aimed to assess the frequency of AEs associated with DT.

DESIGN: This study type is a systematic review and meta-analysis.

DATA SOURCES AND METHODS: Four databases were searched for articles. Randomized trials, single-arm trials, and prospective and retrospective observational studies were included. The type of cancer, previous treatment, and performance status were not questioned. Major AE indicators such as any AE and the pooled frequency of each specific AE were used as outcomes. As a subgroup analysis, we also compared cases in which DT was performed as first-line treatment with those in which it was performed as second-line or later treatment. The protocol for this systematic review was registered on the University Hospital Medical Information Network (UMIN) Center website (ID: UMIN000046751).

RESULTS: Forty-one populations including 3099 patients were selected from 30 articles. Pooled frequencies of key AE indicators are shown below: any AEs, 77.8% [95% confidence interval (CI): 67.9-87.6]; grade ⩾ 3 AEs, 29.3% (95% CI: 24.2-34.4); serious AEs, 34.9% (95% CI: 28.1-41.7); AE leading to discontinuation, 13.3% (95% CI: 9.3-17.4); treatment-related deaths, 0.98% (95% CI: 0.5-1.5). AEs with a frequency exceeding 15% are shown below: fatigue, 30.1% (95% CI: 23.8-36.3); diarrhea, 21.7% (95% CI: 17.8-25.6); pruritus 17.9% (95% CI: 14.4-21.3); decreased appetite, 17.7% (95% CI: 13.7-22.0); nausea, 15.6% (95% CI: 12.1-19.6). There were no significant differences in these pooled frequencies between subgroups.

CONCLUSIONS: The incidence of any AE in DT therapy was approximately 78%, and the incidence of grade 3 or higher AEs was approximately 30%, which was independent of prior therapy.

PMID:37720498 | PMC:PMC10501063 | DOI:10.1177/17588359231198453

Cureus. 2023 Aug 15;15(8):e43540. doi: 10.7759/cureus.43540. eCollection 2023 Aug.

ABSTRACT

Terbutaline sulfate is a beta-adrenergic receptor agonist. More specific for B2 receptors, it is used as a bronchodilator in asthma. Its known side effects can include dizziness, tremors, and tachycardia. However, seizures are not among the commonly reported side effects. This is the case of a five-month-old girl who presented with focal seizures after the intake of terbutaline sulfate syrup. Other causes of the seizures were excluded through history and investigations, including an EEG and electrolyte panel. The seizures stopped on cessation of the terbutaline sulfate with no recurrence, leading us to believe that the focal seizures were an adverse effect of the terbutaline sulfate. A high index of suspicion for drug-related adverse effects should therefore be kept for a child with new onset focal seizures.

PMID:37719479 | PMC:PMC10503665 | DOI:10.7759/cureus.43540

Surg Oncol Clin N Am. 2023 Oct;32(4):631-646. doi: 10.1016/j.soc.2023.05.001. Epub 2023 Jun 15.

ABSTRACT

The primary prevention of breast cancer is a worthwhile goal for which the efficacy of antiestrogens is well established. However, implementation has been problematic related to low prioritization by providers and the reluctance of high-risk women to experience medication side effects. Emerging solutions include improved risk estimation through the use of polygenic risk scores and the application of radiomics to screening mammograms; and optimization of medication dose to limit toxicity. The identification of agents to prevent estrogen receptor negative or HER2-positive tumors is being pursued, but personalization of medical risk reduction requires the prediction of tumor subtypes.

PMID:37714633 | DOI:10.1016/j.soc.2023.05.001

Dent Clin North Am. 2023 Oct;67(4):649-651. doi: 10.1016/j.cden.2023.05.018. Epub 2023 Jun 18.

ABSTRACT

The dental provider should be aware of the oral manifestations of systemic lupus erythematosus (SLE). Patients with SLE may be on chronic oral corticosteroids, which can increase the risk for periodontitis and opportunistic oral infections in addition to inducing multiple systemic adverse effects. Disease complications such as lupus nephritis and comorbid antiphospholipid antibody syndrome can further impact dental decision-making including around medications to prescribe or hemostatic measures to employ during treatment. Patients with SLE on systemic corticosteroid therapy usually do not require steroid supplementation before or after non-surgical or surgical dental treatment.

PMID:37714616 | DOI:10.1016/j.cden.2023.05.018

Dent Clin North Am. 2023 Oct;67(4):593-596. doi: 10.1016/j.cden.2023.05.008. Epub 2023 Jul 3.

ABSTRACT

Oral health care providers should obtain comprehensive medical records from patients with hyperthyroidism before dental treatments. Graves disease is the most common cause of hyperthyroidism. Untreated hyperthyroidism can lead to dangerous adverse effects, such as coma or death. Recognizing early signs and symptoms of hyperthyroidism is crucial in reducing complications.

PMID:37714602 | DOI:10.1016/j.cden.2023.05.008

Dent Clin North Am. 2023 Oct;67(4):561-564. doi: 10.1016/j.cden.2023.05.001. Epub 2023 Jun 18.

ABSTRACT

Patients with a history of stroke often present with numerous neurologic deficits and varying degrees of disability. Ambulation problems requiring the use of a wheelchair can make accessing and receiving dental care difficult for these patients. Side effects from medications can compromise their oral health and complicate care. Possible dexterity limitations decrease their ability to maintain their oral health. Innovative care plans and adaptations may be needed to accommodate the needs of these patients but care generally can be provided safely and effectively in the outpatient dental setting.

PMID:37714594 | DOI:10.1016/j.cden.2023.05.001

Medicine (Baltimore). 2023 Sep 15;102(37):e35187. doi: 10.1097/MD.0000000000035187.

ABSTRACT

Our previous study demonstrated that beneficial effect of β-blockers on clinical outcomes in patients with ST elevation myocardial infarction (STEMI). In clinical practice, β-blocker treatment is occasionally discontinued due to their side effect. The purpose of this study is to assess the impact of discontinuation of β-blockers on long-term clinical outcomes in patients with STEMI. We analyzed the data and clinical outcomes of 901 patients (716 males, 58 ± 13-year-old) STEMI patients who underwent successful primary percutaneous coronary intervention. At discharge of index STEMI, 598 patients were treated with β-blockers (491 males, 56 ± 12-year-old). After more than 1-month β-blocker treatment, β-blockers were stopped in 188 patients for any reason. We classified patients into continuation of β-blockers (410 patients, 56 ± 12-year-old) and discontinuation of β-blockers groups (188 patients, 57 ± 11-year-old) according to discontinuation of β-blockers. Occurrence of major adverse cardiovascular events (MACEs; death, recurrent MI and target vessel revascularization) during up to 10 years of follow-up was evaluated. Mean follow-up month was 56 ± 28 month. In 132 patients (22%), MACEs were occurred. The MACE-free survival rates in the 2 groups were not statistically different (log-rank P = .461). Adjusted hazard ratio (HR) of discontinuation of β-blockers for MACEs was 1.006 (95% confidence interval (CI) 0.701-1.445, P = .973; all cause of death, HR = 0.942, 95% CI = 0.547-1.622, P = .828; recurrent MI, HR = 0.476, 95% CI = 0.179-1.262, P = .136; target vessel revascularization, HR = 1.417, 95% CI = 0.865-2.321, P = .166). The MACE-free survival and survival rates of the non β-blockers treatment group was significantly worse than the discontinuation of β-blockers group (log-rank P = .003 and < 0.001, respectively). This study demonstrated that discontinuation of β-blockers was not associated with adverse cardiovascular outcomes after STEMI. The beneficial effect of β-blockers on clinical outcomes may persist in patients with initial β-blockers treatment at index STEMI.

PMID:37713877 | DOI:10.1097/MD.0000000000035187

J Clin Invest. 2023 Sep 15;133(18):e172058. doi: 10.1172/JCI172058.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a progressive scarring disease of the lung with poor survival. The incidence and mortality of IPF are rising, but treatment remains limited. Currently, two drugs can slow the scarring process but often at the expense of intolerable side effects, and without substantially changing overall survival. A better understanding of mechanisms underlying IPF is likely to lead to improved therapies. The current paradigm proposes that repetitive alveolar epithelial injury from noxious stimuli in a genetically primed individual is followed by abnormal wound healing, including aberrant activity of extracellular matrix-secreting cells, with resultant tissue fibrosis and parenchymal damage. However, this may underplay the importance of the vascular contribution to fibrogenesis. The lungs receive 100% of the cardiac output, and vascular abnormalities in IPF include (a) heterogeneous vessel formation throughout fibrotic lung, including the development of abnormal dilated vessels and anastomoses; (b) abnormal spatially distributed populations of endothelial cells (ECs); (c) dysregulation of endothelial protective pathways such as prostacyclin signaling; and (d) an increased frequency of common vascular and metabolic comorbidities. Here, we propose that vascular and EC abnormalities are both causal and consequential in the pathobiology of IPF and that fuller evaluation of dysregulated pathways may lead to effective therapies and a cure for this devastating disease.

PMID:37712420 | PMC:PMC10503802 | DOI:10.1172/JCI172058

Front Immunol. 2023 Aug 25;14:1225025. doi: 10.3389/fimmu.2023.1225025. eCollection 2023.

ABSTRACT

INTRODUCTION: Natural killer (NK) cells can both amplify and regulate immune responses to vaccination. Studies in humans and animals have observed NK cell activation within days after mRNA vaccination. In this study, we sought to determine if baseline NK cell frequencies, phenotype, or function correlate with antibody responses or inflammatory side effects induced by the Pfizer-BioNTech COVID-19 vaccine (BNT162b2).

METHODS: We analyzed serum and peripheral blood mononuclear cells (PBMCs) from 188 participants in the Prospective Assessment of SARS-CoV-2 Seroconversion study, an observational study evaluating immune responses in healthcare workers. Baseline serum samples and PBMCs were collected from all participants prior to any SARS-CoV-2 infection or vaccination. Spike-specific IgG antibodies were quantified at one and six months post-vaccination by microsphere-based multiplex immunoassay. NK cell frequencies and phenotypes were assessed on pre-vaccination PBMCs from all participants by multi-color flow cytometry, and on a subset of participants at time points after the 1st and 2nd doses of BNT162b2. Inflammatory side effects were assessed by structured symptom questionnaires, and baseline NK cell functionality was quantified by an in vitro killing assay on participants that reported high or low post-vaccination symptom scores.

RESULTS: Key observations include: 1) circulating NK cells exhibit evidence of activation in the week following vaccination, 2) individuals with high symptom scores after 1st vaccination had higher pre-vaccination NK cytotoxicity indices, 3) high pre-vaccination NK cell numbers were associated with lower spike-specific IgG levels six months after two BNT162b2 doses, and 4) expression of the inhibitory marker NKG2A on immature NK cells was associated with higher antibody responses 1 and 6 months post-vaccination.

DISCUSSION: These results suggest that NK cell activation by BNT162b2 vaccination may contribute to vaccine-induced inflammatory symptoms and reduce durability of vaccine-induced antibody responses.

PMID:37711632 | PMC:PMC10497936 | DOI:10.3389/fimmu.2023.1225025

J Coll Physicians Surg Pak. 2023 Jan;33(1):80-82. doi: 10.29271/jcpspcr.2023.80.

ABSTRACT

From the perspective of forensic medicine, substance abuse is an important topic due to its nature and consequences. The usage of methamphetamine is a significant public health problem with deleterious side effects, one of the most serious of which is mimicking central nervous system infection. A 40-year man was brought to the emergency department with complaints of headache, vomiting, fever, and loss of consciousness. According to his relative, he had abstained from methamphetamine abuse for two weeks. The initial diagnosis was made of methamphetamine withdrawal symptoms. However, computed tomography of the head revealed sinusitis and a hypodense lesion with dimensions of 35 x 35 mm. Moreover, Streptococcus agalactiae (group B streptococcus) was grown in the blood culture. A diagnosis of brain abscess and ventriculitis was made. The aim of this report is to draw physicians attention to substance abstinence symptoms that may mask more serious diseases. Key Words: Brain abscess, Methamphetamine withdrawal, Sinusitis.

PMID:37710949 | DOI:10.29271/jcpspcr.2023.80