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Aortic Stenosis (AS) is a common condition with an estimated pooled prevalence of all AS in the elderly population at around 12.4%, with that of severe AS estimated to be around 3.4%. In the past, surgical aortic valve replacement was the primary treatment option for severe AS for decades. However, with the compelling evidence on the safety and efficacy of transcatheter aortic valve replacement (TAVR), it has become the gold standard treatment option for many patients with symptomatic severe AS. Transfemoral access has been the preferred method for transcatheter heart valve delivery. However, the prevalent use of TAVR on a diverse patient profile with different risk factors, such as peripheral artery disease, precluded the possibility of a transfemoral approach despite the improvement of valves and delivery systems technology. Therefore, alternative TAVR approaches have gained increasing utility in cases where transfemoral access is unfavorable. We review the journey, evolution, and techniques for different approaches of percutaneous TAVR, including transfemoral, transcarotid, transsubclavian/transaxillary, and transcaval approaches, in addition to the traditional "surgical" transaortic and transapical accesses. Consolidating these data highlights each approach's practicality and limitations, providing additional grounding for case-by-case utilization and future clinical research.
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BACKGROUND AND OBJECTIVES: It is commonly taught that thyroid eye disease (TED) causes enlargement of the extraocular muscles (EOMs) in the following descending order: inferior rectus (IR), medial rectus (MR), superior rectus (SR), lateral rectus (LR), superior oblique (SO) and inferior oblique (IO). However, with recent literature challenging this notion, we aimed to compare EOM volumes in our cohort of TED patients. Methods: We conducted a retrospective, non-randomized case-control study. Twenty-eight orbits from 28 unique patients with TED who had high-resolution CT scans were compared to 31 normal orbits, all from a single academic institution. Orbital soft tissues were manually segmented using ITK-SNAP 3.8.0 (http://itksnap.org), and soft tissue volumes of the control and TED orbits were compared using independent-sample t-tests. RESULTS: Of the TED orbits, 54% of SR/levator palpebrae superioris complex volumes (SRC) and 50% of IR volumes were greater than two standard deviations above the normal orbit average. Compared to controls, the mean SRC volume in TED subjects was 2.3 times enlarged, followed by the IR (2.1 times), SO (1.8 times), MR (1.7 times), LR (1.6 times), IO (1.6 times), and orbital fat (1.4 times) (p < 0.01 for all). Conclusions: Our findings suggest that contrary to previous teaching, the SRC may be the most severely affected in TED.
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The serum levels of iron, zinc and copper in patients with leukoplakia, oral submucous fibrosis (OSMF) and oral squamous cell carcinoma (OSCC) and compare them with normal subjects is of interest to dentists. The effort was to determine a parameter that will aid the initial diagnosis, a more efficient therapy plan, and ultimately a better prognosis. Participants in the study comprised 40 healthy normal volunteers, 60 patients diagnosed with leukoplakia, 60 patients diagnosed with OSCC, and 60 patients diagnosed with OSMF. After fasting for the whole night, blood samples were taken from each participant. There was analysis by inductively coupled plasma-optical emission spectrometry (ICP-OES) for the determination of trace elements; iron, copper, and zinc. The serum levels of iron and zinc in normal subjects was greater as compared to patients with leukoplakia, OSMF and OSCC. There was increase in serum copper levels in patients with oral leukoplakia, OSMF and OSCC as compared with normal subjects.
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BACKGROUND: The clinical benefit of coronavirus disease 2019 (COVID-19) treatments against new circulating variants remains unclear. We sought to describe characteristics and clinical outcomes of highest risk patients with COVID-19 receiving early COVID-19 treatments in Scotland. METHODS: Retrospective cohort study of non-hospitalized patients diagnosed with COVID-19 from December 1, 2021-October 25, 2022, using Scottish administrative health data. We included adult patients who met ≥ 1 of the National Health Service highest risk criteria for early COVID-19 treatment and received outpatient treatment with sotrovimab, nirmatrelvir/ritonavir or molnupiravir, or no early COVID-19 treatment. Index date was defined as the earliest of COVID-19 diagnosis or early COVID-19 treatment. Baseline characteristics and acute clinical outcomes in the 28 days following index were reported. Values of ≤ 5 were suppressed. RESULTS: In total, 2548 patients were included (492: sotrovimab, 276: nirmatrelvir/ritonavir, 71: molnupiravir, and 1709: eligible highest risk untreated). Patients aged ≥ 75 years accounted for 6.9% (n = 34/492), 21.0% (n = 58/276), 16.9% (n = 12/71) and 13.2% (n = 225/1709) of the cohorts, respectively. Advanced renal disease was reported in 6.7% (n = 33/492) of sotrovimab-treated and 4.7% (n = 81/1709) of untreated patients, and ≤ 5 nirmatrelvir/ritonavir-treated and molnupiravir-treated patients. All-cause hospitalizations were experienced by 5.3% (n = 25/476) of sotrovimab-treated patients, 6.9% (n = 12/175) of nirmatrelvir/ritonavir-treated patients, ≤ 5 (suppressed number) molnupiravir-treated patients and 13.3% (n = 216/1622) of untreated patients. There were no deaths in the treated cohorts; mortality was 4.3% (n = 70/1622) among untreated patients. CONCLUSIONS: Sotrovimab was often used by patients who were aged < 75 years. Among patients receiving early COVID-19 treatment, proportions of 28-day all-cause hospitalization and death were low.
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Antivirais , Tratamento Farmacológico da COVID-19 , COVID-19 , Progressão da Doença , SARS-CoV-2 , Humanos , Antivirais/uso terapêutico , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , SARS-CoV-2/efeitos dos fármacos , COVID-19/mortalidade , Adulto , Resultado do Tratamento , Escócia/epidemiologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Ritonavir/uso terapêutico , Idoso de 80 Anos ou mais , Citidina/análogos & derivados , HidroxilaminasRESUMO
Complement cascade is a defence mechanism useful for eliminating pathogenic microorganisms and damaged cells. However, activation of alternative complement system can also cause inflammation and promote kidney and retinal disease progression. Inflammation causes tissue hypoxia, which induces hypoxia-inducible factor (HIF) and HIF helps the body to adapt to inflammation. In this study, we investigated the effect of HIF stabilizer desidustat in complement-mediated diseases. Oral administration of desidustat (15 mg/kg) was effective to reduce the kidney injury in mice that was induced by either lipopolysaccharide (LPS), doxorubicin or bovine serum albumin (BSA)-overload. Complement activation-induced membrane attack complex (MAC) formation and factor B activity were also reduced by desidustat treatment. In addition, desidustat was effective against membranous nephropathy caused by cationic BSA and retinal degeneration induced by sodium iodate in mice. C3-deposition, proteinuria, malondialdehyde, and interleukin-1ß were decreased and superoxide dismutase was increased by desidustat treatment in cBSA-induced membranous nephropathy. Desidustat specifically inhibited alternative complement system, without affecting the lectin-, or classical complement pathway. This effect appears to be mediated by inhibition of factor B. These data demonstrate the potential therapeutic value of HIF stabilization by desidustat in treatment of complement-mediated diseases.
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Adiponectin plays key roles in energy metabolism and ameliorates inflammation, oxidative stress, and mitochondrial dysfunction via its primary receptors, adiponectin receptors -1 and 2 (AdipoR1 and AdipoR2). Systemic depletion of adiponectin causes various metabolic disorders, including MASLD; however adiponectin supplementation is not yet achievable owing to its large size and oligomerization-associated complexities. Small-molecule AdipoR agonists, thus, may provide viable therapeutic options against metabolic disorders. Using a novel luciferase reporter-based assay here, we have identified Apigenin-6-C-glucoside (ACG), but not apigenin, as a specific agonist for the liver-rich AdipoR isoform, AdipoR2 (EC50: 384 pM) with >10000X preference over AdipoR1. Immunoblot analysis in HEK-293 overexpressing AdipoR2 or HepG2 and PLC/PRF/5 liver cell lines revealed rapid AMPK, p38 activation and induction of typical AdipoR targets PGC-1α and PPARα by ACG at a pharmacologically relevant concentration of 100 nM (reported cMax in mouse; 297 nM). ACG-mediated AdipoR2 activation culminated in a favorable modulation of key metabolic events, including decreased inflammation, oxidative stress, mitochondrial dysfunction, de novo lipogenesis, and increased fatty acid ß-oxidation as determined by immunoblotting, QRT-PCR and extracellular flux analysis. AdipoR2 depletion or AMPK/p38 inhibition dampened these effects. The in vitro results were recapitulated in two different murine models of MASLD, where ACG at 10 mg/kg body weight robustly reduced hepatic steatosis, fibrosis, proinflammatory macrophage numbers, and increased hepatic glycogen content. Together, using in vitro experiments and rodent models, we demonstrate a proof-of-concept for AdipoR2 as a therapeutic target for MASLD and provide novel chemicobiological insights for the generation of translation-worthy pharmacological agents.
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Apigenina , Glucosídeos , Receptores de Adiponectina , Receptores de Adiponectina/agonistas , Receptores de Adiponectina/metabolismo , Animais , Humanos , Camundongos , Apigenina/farmacologia , Apigenina/uso terapêutico , Glucosídeos/farmacologia , Glucosídeos/uso terapêutico , Masculino , Células Hep G2 , Células HEK293 , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Proteínas Quinases Ativadas por AMP/metabolismoRESUMO
OBJECTIVE: Sotrovimab, a dual-action, engineered human monoclonal antibody, has been demonstrated to significantly reduce the risk of hospitalisation and death in high-risk patients with COVID-19. Here, we describe the real-world use of, and outcomes from, sotrovimab treatment in Belgium during the Delta and Omicron waves among patients with COVID-19 at high risk of developing severe disease. METHODS: This was a multicentric, single-arm observational cohort study of non-hospitalised patients receiving outpatient sotrovimab treatment between 1 November 2021 and 2 August 2022 at nine hospitals in Belgium. The primary outcomes were all-cause and COVID-19-related hospitalisations and all-cause deaths during the 29-day acute follow-up period from first administration of sotrovimab. RESULTS: A total of 634 patients were included (63.4% aged < 65 years; 50.3% male). A high proportion (67.7%; n = 429/634) of patients were immunocompromised, with 36.9% (n = 234/634) actively treated for malignancy. During the 29-day acute period, 12.5% (n = 79/634) of sotrovimab-treated patients were hospitalised due to any cause (median duration 4 days; median time to hospitalisation 14 days) and 1.1% (n = 7/634) died due to any cause. The proportion of sotrovimab-treated patients experiencing COVID-19-related hospitalisation was highest during the Delta predominance and Delta/BA.1 codominance (both 6.3%) periods. During the BA.1 predominance, BA.1/BA.2 codominance and BA.2/BA.5 codominance periods, COVID-19-related hospitalisations were consistently low (all ≤2.7%). CONCLUSION: This study indicated low rates of COVID-19-related hospitalisations and all-cause deaths in sotrovimab-treated patients in Belgium, including during Omicron subvariant periods, despite over two-thirds of the study population being immunocompromised.
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Anticorpos Monoclonais Humanizados , Tratamento Farmacológico da COVID-19 , COVID-19 , Hospitalização , Humanos , Masculino , Bélgica/epidemiologia , Feminino , Pessoa de Meia-Idade , Anticorpos Monoclonais Humanizados/uso terapêutico , Idoso , COVID-19/mortalidade , COVID-19/epidemiologia , Hospitalização/estatística & dados numéricos , SARS-CoV-2 , Progressão da Doença , Adulto , Estudos de Coortes , Resultado do Tratamento , Índice de Gravidade de Doença , Anticorpos NeutralizantesRESUMO
OBJECTIVE: To describe characteristics and acute clinical outcomes for patients with COVID-19 treated with sotrovimab, nirmatrelvir/ritonavir or molnupiravir, or untreated patients at highest risk per National Health Service (NHS) criteria. METHODS: Retrospective study of non-hospitalized patients between 1 December 2021 and 31 May 2022, using data from the Discover-NOW dataset (North-West London). Included patients were aged ≥12 years and treated with sotrovimab, nirmatrelvir/ritonavir or molnupiravir, or untreated but expected to be eligible for early treatment per NHS highest-risk criteria. COVID-19-related and all-cause hospitalizations were reported for 28 days from COVID-19 diagnosis (index). Subgroup analyses were conducted in patients with advanced renal disease, those aged 18-64 and ≥65 years, and by period of Omicron BA.1, BA.2 and BA.5 (post-hoc exploratory) predominance. RESULTS: Overall, 1503 treated and 4044 eligible high-risk untreated patients were included. A high proportion of patients on sotrovimab had advanced renal disease (29.3%), ≥3 high-risk comorbidities (47.6%) and were aged ≥65 years (36.9%). Five of 696 (0.7%) patients on sotrovimab, <5/337 (0.3-1.2%) on nirmatrelvir/ritonavir, 10/470 (2.1%) on molnupiravir and 114/4044 (2.8%) untreated patients were hospitalized with COVID-19. Similar results were observed across all subgroups. The proportion of patients dying within 28 days of the index period was similarly low across all cohorts (<2%). CONCLUSION: Patients receiving sotrovimab appeared to show evidence of multiple high-risk comorbidities. Low hospitalization rates were observed for all treated cohorts across subgroups and periods of predominant variants of concern. These results require confirmation with comparative effectiveness analyses adjusting for differences in underlying patient characteristics.
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Antivirais , Tratamento Farmacológico da COVID-19 , COVID-19 , Progressão da Doença , SARS-CoV-2 , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Masculino , Antivirais/uso terapêutico , Antivirais/administração & dosagem , Feminino , Adulto , Idoso , COVID-19/epidemiologia , SARS-CoV-2/isolamento & purificação , Adolescente , Adulto Jovem , Inglaterra/epidemiologia , Hospitalização/estatística & dados numéricos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Resultado do Tratamento , Ritonavir/uso terapêutico , Ritonavir/administração & dosagem , Betacoronavirus , Administração Oral , Citidina/análogos & derivados , HidroxilaminasRESUMO
BACKGROUND: To describe outcomes of high-risk patients with coronavirus disease 2019 (COVID-19) treated with sotrovimab, other monoclonal antibodies (mAbs), or antivirals, and patients who did not receive early COVID-19 treatment. We also evaluate the comparative effectiveness of sotrovimab versus no treatment in preventing severe clinical outcomes. METHODS: This observational retrospective cohort study analyzed Mayo Clinic electronic health records. Non-hospitalized adult patients diagnosed with COVID-19 from May 26, 2021 and April 23, 2022 and at high risk of COVID-19 progression were eligible. The primary outcome was 29-day all-cause hospitalization and/or death. Outcomes were described for patients treated with sotrovimab, other mAbs, or antivirals, and eligible but untreated patients, and compared between sotrovimab-treated and propensity score (PS)-matched untreated cohorts. RESULTS: We included 35,485 patients (sotrovimab, 1369; other mAbs, 6488; antivirals, 133; high-risk untreated, 27,495). A low proportion of patients treated with sotrovimab (n = 33/1369, 2.4%), other mAbs (n = 147/6488, 2.3%), or antivirals (n = 2/133, 1.5%) experienced all-cause hospitalization or death. Among high-risk untreated patients, the percentage of all-cause hospitalization or death was 3.3% (n = 910/27,495). In the PS-matched analysis, 2.5% (n = 21/854) of sotrovimab-treated patients experienced all-cause hospitalization and/or death versus 2.8% (n = 48/1708) of untreated patients (difference, -0.4%; p = 0.66). Significantly fewer sotrovimab-treated patients required intensive care unit admission (0.5% vs 1.8%; difference, -1.3%; p = 0.002) or respiratory support (3.5% vs 8.7%; difference, -5.2%; p < 0.001). CONCLUSIONS: There was no significant difference in the proportion of sotrovimab-treated and PS-matched untreated patients experiencing 29-day all-cause hospitalization or mortality, although significantly fewer sotrovimab-treated patients required intensive care unit admission or respiratory support.
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Anticorpos Monoclonais Humanizados , Antivirais , Tratamento Farmacológico da COVID-19 , COVID-19 , Registros Eletrônicos de Saúde , Hospitalização , Humanos , Hospitalização/estatística & dados numéricos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , COVID-19/mortalidade , COVID-19/epidemiologia , COVID-19/prevenção & controle , Estudos Retrospectivos , Antivirais/uso terapêutico , Estados Unidos/epidemiologia , SARS-CoV-2/isolamento & purificação , Adulto , Idoso de 80 Anos ou mais , Resultado do Tratamento , Estudos de Coortes , Anticorpos NeutralizantesRESUMO
Sexual and gender minority (SGM) adults experience poor health outcomes, in part due to frequent avoidance of necessary health care. Little is known, however, about factors contributing to patterns of health care utilization in this population. Using national data from the All of Us Research Program, this study evaluated the prevalence of care avoidance due to patient-clinician identity discordance (PCID) and its association with health care discrimination among SGM adults. Sexual minority (20.0% vs 9.4%; adjusted rate ratio [aRR] = 1.58; 95% CI, 1.49-1.67, P <0.001) and gender minority adults (34.4% vs 10.3%; aRR = 2.00; 95% CI, 1.79-2.21, P <0.001) were significantly more likely than their non-SGM counterparts to report care avoidance due to PCID. Exposure to health care discrimination was also more prevalent in this population and was dose-dependently associated with significantly higher rates of PCID-based care avoidance. Study findings highlight the importance of diversifying the health care workforce, expanding SGM-related clinical training, and preventing health care discrimination against SGM patients.
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Minorias Sexuais e de Gênero , Humanos , Minorias Sexuais e de Gênero/estatística & dados numéricos , Minorias Sexuais e de Gênero/psicologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Estados Unidos , Relações Médico-Paciente , Adulto Jovem , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Adolescente , IdosoRESUMO
Background: Current assessments on topical treatment attributes in actinic keratosis (AK) do not evaluate safety, effectiveness, and satisfaction from both clinician and patient perspectives, creating an unmet need for more comprehensive AK-specific measures that fully capture the patient experience. Objective: To develop an actinic keratosis-specific expert panel questionnaire (AK-EPQ) of patient-reported outcomes and clinician-reported outcomes for use in research studies. Methods: Using interviews of patients with AK and targeted literature reviews, a 9-person consensus panel of dermatologists with expertise in AK treatment was convened to develop the AK-EPQ to assess AK-specific patient-reported outcomes and clinician-reported outcomes. Results: Nine expert advisers achieved consensus on 11 AK-EPQ items that encompass patient and clinician perspectives of treatment-related local skin reactions, clinical and cosmetic outcomes associated with AK, and satisfaction with treatment; the AK-EPQ will be first implemented in the Patient-Reported Outcomes for Actinic Keratosis study (NCT05260073). Limitations: The AK-EPQ does not directly measure quality of life, although it can be used with validated quality of life instruments. Conclusion: The newly developed AK-EPQ elicits insights into the patient and clinician experience with AK treatments. Comparative probing of these perspectives may help optimize precision medicine in AK treatment.
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Importance: Cutaneous squamous cell carcinoma (CSCC) is the second most common malignant disease in the US. Although it typically carries a good prognosis, a subset of CSCCs are highly aggressive, carrying regional and distant metastatic potential. Due to its high incidence, this aggressive subset is responsible for considerable mortality, with an overall annual mortality estimated to equal or even surpass melanoma. Despite this morbidity, CSCC is excluded from national cancer registries, making it difficult to study its epidemiology and outcomes. Therefore, the bulk of the CSCC literature is composed of single-center and multi-institutional retrospective cohort analyses. Given variations in reporting measures and analyses in these studies, interpretability between studies and the ability to pool results are limited. Objective: To define standardized reporting measures for retrospective CSCC studies. Findings: An expert panel was convened to determine standardized guidelines for recording and analyzing retrospective CSCC data. A total of 13 dermatologists and dermatologic surgeons with more than 5 years of posttraining experience and considerable experience with performing CSCC outcomes research were recruited to the panel. Consensus recommendations were achieved for CSCC retrospective study reporting measures, definitions, and analyses. Conclusions and Relevance: The recommendations in this report present the potential to standardize future CSCC retrospective studies. With such standardization, future work may have greater interstudy interpretability and allow for pooled analyses.
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PURPOSE OF REVIEW: In this review, we discuss the status of novel radiation shielding and other methods to reduce radiation exposure and its associated health risks within the CCL. RECENT FINDINGS: There are many devices on the market each with its unique advantages and inherent flaws. Several are available for widespread use with promising data, while others still in development. The field of percutaneous transcatheter interventions includes complex procedures often involving significant radiation exposure. Increased radiation exposes the proceduralist and CCL staff to potential harm from both direct effects of radiation but also from the ergonomic consequences of daily use of heavy personal protective equipment. Here we discuss several innovative efforts to reduce both radiation exposure and orthopedic injury within the CCL that are available, leading to a safer daily routine in a "lead [apron]-free" environment.
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Introduction Sepsis poses a significant threat in Indian hospitals, with high mortality rates and complications. This study explores the correlation between serum albumin levels and sepsis outcomes in an intensive care unit (ICU) setting. The challenges of diagnosing tropical infections further complicate sepsis management in India. Methodology A longitudinal study was conducted at Vinayaka Mission's Kirupananda Variyar Medical College and Hospital, Salem, India. Adult patients admitted between July 2020 and March 2021 with sepsis were included. Serum albumin levels, demographic data, and clinical outcomes were analyzed. The study used a convenient sampling technique with a sample size of 102 patients. Results Among the 102 patients in the ICU, 22 have expired and the mortality rate in the study was 21.6%. Hypoalbuminemia was present in 56.9% (n = 58) of the patients. The mortality rate is higher among the sepsis patients with the occurrence of hypoalbuminemia (29.3%) compared to patients without hypoalbuminemia (11.4%) and the difference in proportion between the two groups was statistically significant (p-value = 0.029). The requirement of vasopressor support is higher among sepsis patients with the occurrence of hypoalbuminemia (56.9%) compared to patients without hypoalbuminemia (27.3%). The chi-square test reveals that the difference in proportion between the two groups was statistically significant (p-value = 0.005). No substantial impact on systemic inflammatory response scores, readmission to ICU, or progression to chronic illness was observed based on albumin levels. Conclusion This study underscores the predictive value of hypoalbuminemia in sepsis outcomes. Patients with decreased albumin levels showed higher mortality rates and increased vasopressor usage. While albumin levels did not significantly influence certain parameters, hypoalbuminemia may serve as an indicator of severity and adverse prognosis in sepsis, emphasizing the need for further research and tailored interventions.
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Acute liver failure (ALF) exemplifies a rapid decline in liver function among individuals with previously healthy livers, often manifesting through symptoms such as jaundice, confusion, and potentially life-threatening complications. Timely medical intervention, and, in severe instances, liver transplantation, are essential for enhancing outcomes and averting further deterioration. While the causes of ALF are multifaceted, in developed nations, it predominantly arises from drug-induced liver injury. Treatment primarily revolves around supportive measures, with severe cases necessitating liver transplantation. In instances where acute overdose with acetaminophen serves as the instigating factor, N-acetylcysteine (NAC) emerges as a pivotal component of management, as indicated by the Rumack-Matthew nomogram. The Rumack-Matthew nomogram guides treatment for acetaminophen overdose by correlating serum levels with the risk of liver damage. If levels exceed a set threshold, NAC is administered to prevent toxicity by replenishing glutathione. The decision to administer NAC is typically guided by this clinical tool, which aids healthcare providers in determining the appropriate course of action. NAC assumes a critical role in ameliorating the detrimental effects of acetaminophen overdose, particularly in averting liver damage, thus holding significant importance in patient care and recovery. While chronic acetaminophen overdose cases leading to ALF may also benefit from NAC, the supporting evidence remains weak. In this context, we present a case of ALF stemming from chronic acetaminophen ingestion, managed with NAC when liver transplantation was not a viable option.
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This cross-sectional study examines self-reported poor or fair health status, frequent mental distress, and depression among transgender and gender-diverse respondents compared with cisgender respondents to the 2014 to 2022 Behavioral Risk Factor Surveillance System.
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Nível de Saúde , Saúde Mental , Pessoas Transgênero , Humanos , Pessoas Transgênero/psicologia , Pessoas Transgênero/estatística & dados numéricos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Adulto JovemRESUMO
Immunotherapies have revolutionized the management of advanced cutaneous malignancies. However, some patients fail to respond to these therapies, others are ineligible because of comorbidities, and a minority of patients experience treatment-limiting systemic immune-related adverse events. To address these issues and expand treatment options for patients with early-stage disease, a variety of immunotherapies are being developed for direct intratumoral administration. Agents including oncolytic viruses, monoclonal antibodies, cytokines, peptides, and pattern-recognition receptor agonists have been engineered to evoke a local immune response while minimizing systemic toxicity and have shown favorable results in preclinical and early clinical testing. This review covers the current landscape of intratumoral immunotherapies for the treatment of cutaneous melanoma, squamous cell carcinoma, and basal cell carcinoma, highlighting the diverse array of agents being explored and their potential benefits and challenges.
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BACKGROUND: The Patient-Reported Outcomes in Actinic Keratosis (PROAK) study evaluated patient- and clinician-reported outcomes (PRO; ClinRO) during 24 weeks of follow-up among adult patients with actinic keratosis (AK) on the face or scalp who were administered tirbanibulin 1% ointment in real-world community practices in the United States. Methods: Quality of life (QoL) was assessed by Skindex-16 at week (W) 8. Additionally, effectiveness (Investigator Global Assessment [IGA]), PRO and ClinRO (Treatment Satisfaction Questionnaire for Medication and Expert Panel Questionnaire), safety, and tolerability were assessed at W8 and W24. RESULTS: The safety population included 300 patients; the full analysis set included 290 patients (278 patients at W24). At W8, a statistically significant difference (P<0.03) was observed for Skindex-16 domains in all assessed subgroups. Clinicians and patients reported high global satisfaction (mean [SD] scores of 74.9 [23.9] and 72.0 [24.6], respectively) at W24. Overall skin appearance improved from baseline to W24 (83.6% clinicians; 78.5% patients). IGA success (IGA score of 0-1) was achieved by 71.9% of patients at W24 with a similar % at W8 (73.8%) suggesting a stable effectiveness over time. About 5% of patients reported at least one adverse event, 4% reported at least one serious adverse event and no patients reported serious adverse drug reactions. At W8, the most frequently reported local skin reactions were mild/moderate erythema (47.6%) and flaking/scaling (49.6%). CONCLUSIONS: Treatment with tirbanibulin demonstrated effectiveness in the management of AK lesions and a favorable safety and tolerability profile. Furthermore, QoL was improved as early as W8, and both patients and clinicians reported high levels of treatment satisfaction, independently of patients' characteristics. J Drugs Dermatol. 2024;23(5):338-346. doi:10.36849/JDD.8264.
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Ceratose Actínica , Medidas de Resultados Relatados pelo Paciente , Satisfação do Paciente , Qualidade de Vida , Humanos , Ceratose Actínica/tratamento farmacológico , Ceratose Actínica/diagnóstico , Masculino , Feminino , Estados Unidos , Idoso , Pessoa de Meia-Idade , Resultado do Tratamento , Idoso de 80 Anos ou mais , Administração Cutânea , Pomadas , Seguimentos , Adulto , Inquéritos e Questionários/estatística & dados numéricosRESUMO
Pancreatitis is a condition much more commonly found in adults, but when diagnosed in the pediatric population, is often due to medications, congenital pathology, and critical illness. This patient had previously undergone treatment with 6-mercaptopurine and presented with pancreatitis that eventually worsened to a walled-off necrotic collection with paracolic extensions reaching the pelvis. Given clinical worsening with development of shock, procedural options for source control were weighed with gastroenterology, pediatric surgery, and interventional radiology, before pancreatic necrosectomy was determined to be the treatment of choice, given the adjacency of the collection to the stomach. A total of three separate endoscopic pancreatic necrosectomy procedures were performed and the patient s clinical status improved greatly, with vast improvement later seen on outpatient imaging. This successful treatment course argues for the efficacy of pancreatic necrosectomy even in very large walled off collections, and most importantly, lead to a positive outcome in this young patient.