Hypofractionated stereotactic photon radiotherapy of choroidal melanoma: 20-year experience.

BACKGROUND: To evaluate the long-term results after hypofractionated stereotactic photon radiotherapy (SRT) in patients with choroidal melanoma treated between 1997 and 2016. MATERIAL AND METHODS: A total of 335 patients (183 male and 152 female) with choroidal melanoma unsuitable for ruthenium-106 brachytherapy or local resection were treated with linear accelerator-based SRT at the Medical University of Vienna. All patients received five fractions with either 10, 12 or 14 Gy per fraction. A complete ophthalmic examination including visual acuity and measurement of the tumor base and height using standardized A- and B-scan ultrasonography was performed every 3 months in the first 2 years, every 6 months until 5 years and yearly thereafter. Early and late adverse side effects were assessed at every follow-up visit. RESULTS: The median overall follow-up was 78.6 months (39.1 to 113.7 months). Local tumor control was 95.4% after 10 and 12 years, respectively. Fifty-four patients developed metastatic disease, and 31 died during the follow-up. Mean visual acuity decreased from 0.55 Snellen at baseline to 0.05 Snellen at the last individual follow-up. Ischemic retinopathy (192/335cases) and optic neuropathy (174/335cases) were the most common radiogenic side effects, followed by radiogenic cataract (n = 127), neovascular glaucoma (n = 71) and corneal epithelium defects (n = 49). Enucleation was performed in 54 patients mostly due to neovascular glaucoma (n = 41) or tumor recurrence (n = 10) during the study period. The eye retention rate was 79.7% after 10 and 12 years. CONCLUSION: Hypofractionated stereotactic photon radiotherapy showed a high rate of local tumor control for choroidal melanoma and an acceptable rate of radiogenic side effects.

Which practices co-deliver food security, climate change mitigation and adaptation, and combat land degradation and desertification?

There is a clear need for transformative change in the land management and food production sectors to address the global land challenges of climate change mitigation, climate change adaptation, combatting land degradation and desertification, and delivering food security (referred to hereafter as "land challenges"). We assess the potential for 40 practices to address these land challenges and find that: Nine options deliver medium to large benefits for all four land challenges. A further two options have no global estimates for adaptation, but have medium to large benefits for all other land challenges. Five options have large mitigation potential (>3 Gt CO2 eq/year) without adverse impacts on the other land challenges. Five options have moderate mitigation potential, with no adverse impacts on the other land challenges. Sixteen practices have large adaptation potential (>25 million people benefit), without adverse side effects on other land challenges. Most practices can be applied without competing for available land. However, seven options could result in competition for land. A large number of practices do not require dedicated land, including several land management options, all value chain options, and all risk management options. Four options could greatly increase competition for land if applied at a large scale, though the impact is scale and context specific, highlighting the need for safeguards to ensure that expansion of land for mitigation does not impact natural systems and food security. A number of practices, such as increased food productivity, dietary change and reduced food loss and waste, can reduce demand for land conversion, thereby potentially freeing-up land and creating opportunities for enhanced implementation of other practices, making them important components of portfolios of practices to address the combined land challenges.

Problems sleeping with prostate cancer: exploring possible risk factors for sleep disturbance in a population-based sample of survivors.

PURPOSE: This study aimed to investigate the prevalence of sleeping problems in prostate cancer survivors and to explore the role of predisposing, precipitating and perpetuating factors in this process. METHODS: Using a cross-sectional design, 3348 prostate cancer survivors between 2 and 18 years post diagnosis reported experiences of insomnia using the QLQC30, along with their sociodemographic characteristics, health status and treatment(s) received. The EQ5D-5L and QLQPR25 assessed survivors' overall and prostate cancer-specific health-related quality of life. A hierarchical multiple regression analysis was constructed with three blocks: (1) predisposing (e.g. demographics at diagnosis), (2) precipitating (e.g. disease extent, treatment) and (3) perpetuating factors (e.g. side effects). RESULTS: Nineteen percent of survivors reported significant problems sleeping. The final model accounted for 31% of the variance in insomnia scores (p < .001). In order of magnitude, associates of sleep disturbance were urinary symptoms (ß = 0.22; p < .001), experiencing symptoms of depression/anxiety (ß = 0.18; p < .001), hormone treatment-related symptoms (ß = 0.12; p = .001), pain (ß = 0.10; p < .001) and bowel symptoms (ß = 0.06; p = .005). Having a lower education and more comorbidities at diagnosis also predicted sleep problems. CONCLUSION: Results suggest that it is the ongoing adverse effects of prostate cancer and its treatment (e.g. urinary symptoms) that put survivors most at risk of sleep problems. Strong associations with symptoms of depression/anxiety were also observed. Findings highlight the need for health care practitioners to treat and manage adverse effects of prostate cancer treatment in order to mitigate sleep disturbance in survivors.

Ipilimumab-induced hypophysitis, a single academic center experience.

BACKGROUND: Immune checkpoint inhibitors, single or in combination, have recently become a cornerstone for the treatment of many malignancies. Ipilimumab, a CTLA-4 inhibitor, was initially FDA approved for treatment of unresectable or metastatic melanoma and subsequently in combination therapy for other cancers. Ipilimumab-induced hypophysitis (IH) risk of development varies in different studies between 0 and 17%. Furthermore, little is known on how to predict which patients will develop IH and its impact on efficacy of Ipilimumab and survival for these patients. Here we reviewed IH and its impact on progression-free survival (PFS) and overall survival (OS). METHODS: Retrospective, IRB- approved review of consecutive 117 melanoma patients who received ipilimumab between 2011 and 2016 was undertaken. Demographic and clinical characteristics, treatment timing and doses, time to progression after therapy, and survival data were reviewed. Patients were predefined in two groups: patients with and without IH. Descriptive statistics were used to summarize the demographic and clinical characteristics of the study sample. All values are shown as means and standard deviation [mean (SD)] unless indicated otherwise. P < 0.05 was considered to be statistically significant. RESULTS: Of the 117 patients, 15 (12.8%) with a median age of 62.1 years developed IH. In the IH cohort, 10 (66.7%) were male and were significantly older than females (median 67.7 vs. 50.8; P = 0.009). This difference was not seen in non-IH group. Male patients with IH were significantly older than males without IH (67.7 vs. 56.4 years, P = 0.020), however this difference was not observed in females. No patient who received prior cancer systemic therapy (0/30) developed IH vs. 17.2% (15/72) without prior therapy developed IH (OR 0.00; 95% CI 0.00 to 0.73, P = 0.011). Between IH and non-IH patients, there was no difference in gender, race, ethnicity, BMI, diabetes or autoimmune disease at baseline, number of administered ipilimumab cycles, presence of primary melanoma lesion, or BRAF status. IH and non-IH patients had a similar median PFS (8.1 vs. 6.8 months, HR = 0.51, 95% CI 0.24 to 1.05 P = 0.062) and OS (53.3 vs. 29.5 months; HR 0.66, 95% CI 0.30 to 1.46; P = 0.307). CONCLUSION: In this study of melanoma patients treated with Ipilimumab, risk of developing IH was high (almost 13%). Older age in men and no prior cancer therapy were associated with IH higher risk. Development of IH was not associated with PFS or OS. Increased use of immune checkpoint inhibitors in the future will impact IH overall risk, thus awareness is needed. Given the lack of reliable identifiable risk factors, close monitoring of signs and symptoms after each therapy cycle is critical for early detection and treatment of hypophysitis.

[Modern treatment of deep vein thrombosis and pulmonary embolism]. / Moderne Therapie tiefer Venenthrombosen und der Lungenarterienembolie.

Virchow's triad has been known for a 100 years. The development of therapeutic possibilities during this time was enormous. Today anticoagulant therapy is much more differentiated. Four new oral substances have replaced the traditional treatment with vitamin K antagonists in angiology. A standardized dosage is available. The monitoring of the coagulation parameters is no longer necessary, but it is important to monitor renal function. Direct oral anticoagulants are approved for the treatment of venous thrombosis and pulmonary embolism, but not during pregnancy or in children. Severe bleeding complications, especially intracerebral bleeding, are less common. The incidence of venous thromboembolism is still high. Obesity and cancer are of particular importance. The "therapeutic pact" with the patient requires that physicians master the art of "talking medicine".

Expecting the worst? The relationship between retrospective and prospective appraisals of illness on quality of life in prostate cancer survivors.

OBJECTIVE: Despite a generally good prognosis, many prostate cancer survivors have poor quality of life (QOL). A greater understanding of how psychological appraisals influence QOL is merited given their potentially modifiable nature. In this study, we considered how elements of survivors' retrospective and prospective appraisals relate to QOL. METHODS: A total of 1229 prostate cancer survivors between 2 and 5 years post-diagnosis, identified from a population-based National Cancer Registry, were asked questions on their socio-demographics, health, treatment received, and adverse-effects using a cross-sectional design. QOL was assessed using the EORTC QLQ-C30. Retrospective appraisals were assessed by asking survivors to reflect on their experience of treatment-related adverse-effects compared with their prior expectations. A fear of recurrence scale assessed prospective appraisals of future disease course. A multiple regression model explored the impact of psychological appraisals on QOL, after controlling for socio-demographic, treatment, and health-related factors. RESULTS: The model was significant explaining 37% of variance in QOL. The strongest associate with QOL was fear of recurrence (ß = -.29; P < .001). Survivors who experienced side effects that were worse than expected had significantly lower QOL (ß = -.10; P = .002). Other significant correlates of lower QOL were presence of comorbidities, having undergone a less invasive treatment, and having more advanced disease. Working at diagnosis and having a higher level of education were significantly associated with higher QOL. CONCLUSIONS: Results suggest both retrospective and prospective appraisals are independently related to QOL in prostate cancer. Providing survivors with more information about possible adverse effects of treatment, as well as providing appropriate information regarding future disease progression, may improve QOL.

NeuroCog FX study: A multicenter cohort study on cognitive dysfunction in patients with early breast cancer.

OBJECTIVE: Complaints about cognitive dysfunction (CD) reportedly persist in approximately one third of breast cancer patients, but the nature of CD and possible risk factors are unknown. METHODS: A cross-sectional, multicenter study was set up at 9 German oncological rehabilitation centers. Objective cognitive performance was assessed by the NeuroCog FX test, a short computerized screening (duration <30 minutes) which assesses working memory, alertness, verbal/figural memory, and language/executive. Patients' test performance was correlated with treatment factors (chemo-, radiotherapy), subjective performance (FEDA), depression (PHQ-9), quality of life (EORTC QLQ-30), and clinical characteristics. RESULTS: From February 2013 to December 2014, a clinically homogenous sample of 476 patients was recruited (early tumor stage [T0-T2]: 93%; node-negative: 67%; chemotherapy: 61%; radiotherapy: 84%). NeuroCog FX could be administered in 439 patients (92%; median age: 50 [24-62] years). Patients showed decreased performance in attentional-executive functions (but not verbal/figural memory) and a 3-fold rate of CD in terms of below average performance in at least 1 cognitive domain (42%). Approximately 40% of the patients also reported subjective cognitive impairment (FEDA). No therapy-specific effect on test performance was obtained in the NeuroCog FX test. CONCLUSIONS: Breast cancer survivors showed objective attentional-executive and subjective cognitive impairments. No therapy-specific adverse side effect on objective cognitive performance was found. Depression strongly contributed to objective and subjective cognitive complaints and reduced quality of life.

Hepatotoxicity by combination treatment of temozolomide, artesunate and Chinese herbs in a glioblastoma multiforme patient: case report review of the literature.

Glioblastoma multiforme (GBM) represents an aggressive tumor type with poor prognosis. The majority of GBM patients cannot be cured. There is high willingness among patients for the compassionate use of non-approved medications, which might occasionally lead to profound toxicity. A 65-year-old patient with glioblastoma multiforme (GBM) has been treated with radiochemotherapy including temozolomide (TMZ) after surgery. The treatment outcome was evaluated as stable disease with a tendency to slow tumor progression. In addition to standard medication (ondansetron, valproic acid, levetiracetam, lorazepam, clobazam), the patient took the antimalarial drug artesunate (ART) and a decoction of Chinese herbs (Coptis chinensis, Siegesbeckia orientalis, Artemisia scoparia, Dictamnus dasycarpus). In consequence, the clinical status deteriorated. Elevated liver enzymes were noted with peak values of 238 U/L (GPT/ALAT), 226 U/L (GOT/ASAT), and 347 U/L (γ-GT), respectively. After cessation of ART and Chinese herbs, the values returned back to normal and the patient felt well again. In the literature, hepatotoxicity is well documented for TMZ, but is very rare for ART. Among the Chinese herbs used, Dictamnus dasycarpus has been reported to induce liver injury. Additional medication included valproic acid and levetiracetam, which are also reported to exert hepatotoxicity. While all drugs alone may bear a minor risk for hepatotoxicity, the combination treatment might have caused increased liver enzyme activities. It can be speculated that the combination of these drugs caused liver injury. We conclude that the compassionate use of ART and Chinese herbs is not recommended during standard radiochemotherapy with TMZ for GBM.

Aqueous extract of Phragmitis rhizoma ameliorates myelotoxicity of docetaxel in vitro and in vivo.

BACKGROUND: A variety of anticancer chemotherapeutics induce adverse side effects including myelotoxicity. Dried roots of Phragmites communis Trinius, Phragmitis rhizoma, have been clinically used in traditional folk medicine to relieve various symptoms like fever. In this study, we evaluated the protective effect of the aqueous extract of Phragmitis rhizoma (EPR) against docetaxel-induced myelotoxicity in vitro and in vivo. METHODS: The in vitro myelo-protective effect of EPR was evaluated using the colony forming unit (CFU) assay with hematopoietic progenitor cells. The in vivo efficacy of EPR was evaluated in myelosuppressed C57BL/6 male mice which were induced by repeated intraperitoneal injections of 30 mg/kg docetaxel for 3 times. EPR was orally administered for 4 days to docetaxel-induced myelosuppressed C57BL/6 male mice which were induced by intraperitoneal injection of 30 mg/kg docetaxel for 3 times: Group 1 (vehicle control, n = 10), Group 2 (docetaxel plus vehicle, n = 10), Group 3 (docetaxel plus EPR 30 mg/kg, n = 10), Group 4 (docetaxel plus EPR 100 mg/kg, n = 10) and Group 5 (docetaxel plus EPR 300 mg/kg, n = 10). Whole blood counts were measured automatically, and immune organs were histologically examined. Expression of immunomodulatory cytokines was measured by quantitative real-time polymerase chain reaction or enzyme-linked immunosorbent assay. The toxicity of EPR itself was evaluated in normal human cell lines including IMR-90, foreskin fibroblast and human umbilical vein endothelial cells. The hepatotoxicity of EPR was predicted by multi-parametric assays involving cell viability, caspase 3/7 activity, GSH contents and LDH leakage using the HepaRG hepatic cell line. RESULTS: Co-treatment of EPR or its major component, p-hydroxycinnamic acid, increased the numbers of hematopoietic CFU counts in the docetaxel-induced in vitro myelotoxicity assay system. The in vitro protective effect of EPR against docetaxel toxicity was replicated in a myelosuppressed animal model: white blood cells, neutrophils, lymphocytes and red blood cells rebounded; bone marrow niche and structural integrity of the thymus were preserved; and the expression of immune-stimulating cytokines including IL3, IL6, SCF and GM-CSF was enhanced. Furthermore, EPR and p-hydroxycinnamic acid promoted the proliferation of primary splenocytes and thymocytes. In the toxicity assays, no remarkable signs related with toxicity were observed in all tested normal human cells and HepaRG. CONCLUSIONS: EPR has the potential to ameliorate docetaxel-mediated myelotoxicity in both in vitro and in vivo models. However, the identification of the responsible active components and the precise underlying myelo-protective mechanism of EPR need to be elucidated before novel drug development using EPR can precede.

Development of a primary cutaneous CD30(+) anaplastic large-cell T-cell lymphoma during treatment of multiple sclerosis with fingolimod.

BACKGROUND: The appearance of solid tumors und lymphomas during treatment with fingolimod was observed in studies and has been described in case reports. OBJECTIVE: To report a case of primary cutaneous CD30(+) anaplastic large-cell T-cell lymphoma during treatment of multiple sclerosis (MS) with fingolimod. METHODS: Case study. RESULTS: Our patient developed a lymphoma a few weeks after initialization of therapy with fingolimod; 5 weeks after discontinuation of treatment the lesions resolved. CONCLUSION: Causality of fingolimod is indicated by the fact that the skin lesions appeared after commencement of treatment and resolved after discontinuation of therapy. This case serves as a reminder of the potential side effects of fingolimod.

Recent clinical trials for the etiological treatment of chronic chagas disease: advances, challenges and perspectives.

Chagas disease, a chronic systemic parasitosis caused by the Kinetoplastid protozoon Trypanosoma cruzi, is the first cause of cardiac morbidity and mortality in poor rural and suburban areas of Latin America and the largest parasitic disease burden in the continent, now spreading worldwide due to international migrations. A recent change in the scientific paradigm on the pathogenesis of chronic Chagas disease has led to a consensus that all T. cruzi-seropositive patients should receive etiological treatment. This important scientific advance has spurred the rigorous evaluation of the safety and efficacy of currently available drugs (benznidazole and nifurtimox) as well as novel anti-T. cruzi drug candidates in chronic patients, who were previously excluded from such treatment. The first results indicate that benznidazole is effective in inducing a marked and sustained reduction in the circulating parasites' level in the majority of these patients, but adverse effects can lead to treatment discontinuation in 10-20% of cases. Ergosterol biosynthesis inhibitors, such as posaconazole and ravuconazole, are better tolerated but their efficacy at the doses and treatment duration used in the initial studies was significantly lower; such results are probably related to suboptimal exposure and/or treatment duration. Combination therapies are a promising perspective but the lack of validated biomarkers of response to etiological treatment and eventual parasitological cures in chronic patients remains a serious challenge.

Outcomes of severely ill patients with AIDS treated with efavirenz or dolutegravir: a multicenter, observational study.

Background: Currently, integrase inhibitors (INIs)-based ART regimens are the preferred initial therapy for AIDS patients. There is scarce information on the use of dolutegravir (DTG) among late-presenter people living with HIV (PLHIV). Objectives: To compare the effect of DTG- or efavirenz (EFV)-based regimens on the outcomes of patients with advanced AIDS. Methods: We compared two cohorts of consecutive symptomatic AIDS patients (WHO stage 4, CD4 count<50 cells/mL) starting therapy with DTG-based (2018-2021, prospective cohort) or EFV-based regimens (2013-2016, retrospective cohort) from five Brazilian cities. The main endpoints were early (all-cause) mortality, viral suppression at 24 and 48 weeks, changes in CD4 count, and changes in initial therapy (for any reason). Results: We included all eligible patients in a consecutive way (in both groups) until we reached 92 individuals per arm. The median baseline CD4 count (20 vs. 21 cells/mL) and the median HIV plasma viral load (5.5 copies/mL log10) were identical across the groups. Viral suppression rates were higher in the DTG group than in the EFV group at 24 (67.4% vs. 42.4%,) and 48 weeks (65.2% vs. 45.7%, p < 0.001 for both comparisons). More patients in the DTG group presented with CD4 > 200 cells/mL compared to the EFV group at 48 weeks (45% vs. 29%, p = 0.03). Treatment changes (ITT, M = F) were significantly more frequent in the EFV group (1% vs. 17%, p < 0.0001). The relative mortality rate was 25% lower in the DTG group, but without statistical significance. Conclusion: We detected a higher rate of virological suppression and greater treatment durability in patients with advanced AIDS treated with DTG than in those treated with EFV.

Pharmacovigilance of esketamine nasal spray: an analysis of the FDA adverse event reporting system database.

Esketamine nasal spray (ESK-NS) is a new drug for treatment-resistant depression, and we aimed to detect and characterize the adverse events (AEs) of ESK-NS using the Food and Drug Administration (FDA) adverse event reporting system (FAERS) database between 2019 Q1 and 2023 Q4. Reporting odds ratio (ROR), proportional reporting ratio (PRR), and multi-item gamma Poisson shrinker (MGPS) were performed to detect risk signals from the FAERS data to identify potential ESK-NS-AEs associations. A total of 14,606 reports on AEs with ESK-NS as the primary suspected drug were analyzed. A total of 518 preferred terms signals and 25 system organ classes mainly concentrated in psychiatric disorders (33.20%), nervous system disorders (16.67%), general disorders and administration site conditions (14.21%), and others were obtained. Notably, dissociation (n = 1,093, ROR 2,257.80, PRR 899.64, EBGM 876.86) exhibited highest occurrence rates and signal intensity. Moreover, uncommon but significantly strong AEs signals, such as hand-eye coordination impaired, feeling guilty, and feelings of worthlessness, were observed. Additionally, dissociative disorder (n = 57, ROR 510.92, PRR 506.70, EBGM 386.60) and sedation (n = 688, ROR 172.68, PRR 155.53, and EBGM 142.05) both presented strong AE signals, and the former is not recorded in the Summary of Product Characteristics (SmPC). In clinical applications, close attention should be paid to the psychiatric disorders and nervous system disorders, especially dissociation. Meanwhile, clinical professionals should be alert for the occurrence of AEs signals not mentioned in the SmPC and take preventive measures to ensure the safety of clinical use.

Active monitoring of antifungal adverse events in hospitalized patients based on Global Trigger Tool method.

Background: The increasing prevalence of fungal infections necessitates broader use of antifungal medications. However, the prevalence of adverse drug events (ADEs) restricts their clinical application. This study aimed to develop a reliable ADEs trigger for antifungals to enable proactive ADEs monitoring, serving as a reference for ADEs prevention and control. Methods: This investigation comprises two phases. Initially, the trigger was established via a literature review, extraction of relevant items, and refinement through Delphi expert consultation. Subsequently, the validity of the trigger was assessed by analyzing hospital records of antifungal drug users from 1 January 2019 to 31 December 2020. The correlation between each trigger signal and ADEs occurrence was examined, and the sensitivity and specificity of the trigger were evaluated through the spontaneous reporting system (SRS) and Global Trigger Tool (GTT). Additionally, risk factors contributing to adverse drug events (ADEs) resulting from antifungal use were analyzed. Results: Twenty-one preliminary triggers were refined into 21 final triggers after one expert round. In the retrospective analysis, the positive trigger rate was 65.83%, with a positive predictive value (PPV) of 28.75%. The incidence of ADEs in inpatients was 28.75%, equating to 44.58 ADEs per 100 admissions and 33.04 ADEs per 1,000 patient days. Predominant ADEs categories included metabolic disturbances, gastrointestinal damage, and skin rashes. ADEs severity was classified into 36 cases at grade 1, 160 at grade 2, and 18 at grade 3. The likelihood of ADEs increased with longer stays, more positive triggers, and greater comorbidity counts. Conclusion: This study underscores the effectiveness of the GTT in enhancing ADEs detection during antifungal medication use, thereby confirming its value as a monitoring tool.

Advances in local drug delivery technologies for improved rheumatoid arthritis therapy.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by an inflammatory microenvironment and cartilage erosion within the joint cavity. Currently, antirheumatic agents yield significant outcomes in RA treatment. However, their systemic administration is limited by inadequate drug retention in lesion areas and non-specific tissue distribution, reducing efficacy and increasing risks such as infection due to systemic immunosuppression. Development in local drug delivery technologies, such as nanostructure-based and scaffold-assisted delivery platforms, facilitate enhanced drug accumulation at the target site, controlled drug release, extended duration of the drug action, reduced both dosage and administration frequency, and ultimately improve therapeutic outcomes with minimized damage to healthy tissues. In this review, we introduced pathogenesis and clinically used therapeutic agents for RA, comprehensively summarized locally administered nanostructure-based and scaffold-assisted drug delivery systems, aiming at improving the therapeutic efficiency of RA by alleviating the inflammatory response, preventing bone erosion and promoting cartilage regeneration. In addition, the challenges and future prospects of local delivery for clinical translation in RA are discussed.

Interferon therapy and its association with depressive disorders - A review.

Interferons (IFNs) are important in controlling the innate immune response to viral infections. Besides that, studies have found that IFNs also have antimicrobial, antiproliferative/antitumor and immunomodulatory effects. IFNs are divided into Type I, II and III. Type I IFNs, in particular IFN-α, is an approved treatment for hepatitis C. However, patients developed neuropsychological disorders during treatment. IFN-α induces proinflammatory cytokines, indoleamine 2,3-dioxygenase (IDO), oxidative and nitrative stress that intensifies the body's inflammatory response in the treatment of chronic inflammatory disease. The severity of the immune response is related to behavioral changes in both animal models and humans. Reactive oxygen species (ROS) is important for synaptic plasticity and long-term potentiation (LTP) in the hippocampus. However, excess ROS will generate highly reactive free radicals which may lead to neuronal damage and neurodegeneration. The limbic system regulates memory and emotional response, damage of neurons in this region is correlated with mood disorders. Due to the drawbacks of the treatment, often patients will not complete the treatment sessions, and this affects their recovery process. However, with proper management, this could be avoided. This review briefly describes the different types of IFNs and its pharmacological and clinical usages and a focus on IFN-α and its implications on depression.

Atrial fibrillation induced by gabapentin: a case report.

BACKGROUND: Gabapentin is commonly prescribed for the treatment of neuropathic pain, restless leg syndrome, and partial-onset seizures. Although the most frequent side effects of gabapentin are associated with the central nervous system, gabapentin can also affect the cardiovascular system. Case reports and observational studies have showed that gabapentin can be associated with increased risk of atrial fibrillation. However, all the evidence is concentrated in patients older than 65 years old with comorbidities that predispose them to the development of arrhythmias. CASE PRESENTATION: We describe a case of an African American male in his 20s that presented to our chronic pain clinic with lumbar radiculitis and developed atrial fibrillation 4 days after being started on gabapentin. Laboratory workup did not show significant abnormalities, including normal complete blood count, comprehensive metabolic panel, toxicology screen, and thyroid-stimulating hormone. Transthoracic and transesophageal echocardiography showed a patent foramen ovale with right-to-left shunt. The patient was initially treated with diltiazem for heart rate control and apixaban. Direct current cardioversion with successful conversion to sinus rhythm was performed 24 hours after admission. The patient was then discharged on apixaban and diltiazem. Apixaban was changed to low-dose aspirin 1 month after discharge. CONCLUSION: With rapidly increasing usage of gabapentin for approved and off-label indications, it is important to identify unintended adverse effects of this drug as they are considered safe alternatives to opioids. New-onset atrial fibrillation could be induced by gabapentin in young individuals.

Characterization of immunomodulatory factors and cells in bronchoalveolar lavage fluid for immune checkpoint inhibitor-related pneumonitis.

As immune checkpoint inhibitors (ICIs) are widely used, a series of immune-related adverse events (irAEs) have been reported, including immune checkpoint inhibitor-related pneumonitis (ICI-pneumonitis). The incidence of ICI-pneumonitis is higher in reality than in clinical trials. The diagnosis is challenging, mainly based on clinical and imaging features, and requires the exclusion of other causes. The data on the biological mechanisms of ICI-pneumonitis are scarce, resulting in little knowledge of the best treatment for ICI-pneumonitis. Bronchoalveolar lavage (BAL) may be helpful to identify the biological differences or find predictive biomarkers, and may in turn help to develop phenotype-specific targeted drugs to treat ICI-pneumonitis. Herein, we outline the characterization of immunomodulatory factors and cells in bronchoalveolar lavage fluid for ICI-pneumonitis. Through careful sorting and literature review, we find crosstalk between pathogenic Th17/Th1 cells (i.e., Th17.1) and pro-inflammatory monocytes, and activation of Th17(/Th1)/IL-17A (/IFN-γ) pathways may play a key role in the pathogenesis of ICI-pneumonitis. Disruption of the interaction between pathogenic Th17/Th1 cells and pro-inflammatory monocytes (such as, anti-IL-23) may be a potential treatment for ICI-pneumonitis. We first describe the possible pathophysiological mechanisms of ICI-pneumonitis, hoping to contribute to the optimization of diagnosis and treatment, as well as provide readers with research inspiration.

Symptomatic dermographism induced by oral minocycline: A report of four cases.

Symptomatic dermographism (SD) is the most common form of chronic inducible urticarias. The etiology of this disease has rarely been reported in the literature. Minocycline is widely used in the treatment of acne, rosacea, and other inflammatory skin diseases. Herein we report four cases of SD onset during minocycline administration. These were young women in their 20s to 30s who were taking minocycline orally for acne vulgaris or rosacea. They all experienced the onset of SD 2-3 weeks after taking the drug, and then the complete disappearance of SD 1 month after stopping the drug. Minocycline was thought to be the culprit drug in these cases as other drugs were ruled out on clinical grounds. Our small series suggests that oral minocycline may induce SD, thus raising the awareness of this association in clinical practice. More research is needed to further confirm this association and reveal the underlying mechanism(s).

How Should Doctors Frame the Risk of a Vaccine's Adverse Side Effects? It Depends on How Trustworthy They Are.

BACKGROUND: How health workers frame their communication about vaccines' probability of adverse side effects could play an important role in people's intentions to be vaccinated (e.g., positive frame: side effects are unlikely v. negative frame: there is a chance of side effects). Based on the pragmatic account of framing as implicit advice, we expected that participants would report greater vaccination intentions when a trustworthy physician framed the risks positively (v. negatively), but we expected this effect would be reduced or reversed when the physician was untrustworthy. DESIGN: In 4 online experiments (n = 191, snowball sampling and n = 453, 451, and 464 UK residents via Prolific; Mage≈ 34 y, 70% women, 84% White British), we manipulated the trustworthiness of a physician and how they framed the risk of adverse side effects in a scenario (i.e., a chance v. unlikely adverse side effects). Participants reported their vaccination intention, their level of distrust in health care systems, and COVID-19 conspiracy beliefs. RESULTS: Physicians who were trustworthy (v. untrustworthy) consistently led to an increase in vaccination intention, but the way they described adverse side effects mattered too. A positive framing of the risks given by a trustworthy physician consistently led to increased vaccination intention relative to a negative framing, but framing had no effect or the opposite effect when given by an untrustworthy physician. The exception to this trend occurred in unvaccinated individuals in experiment 3, following serious concerns about one of the COVID vaccines. In that study, unvaccinated participants responded more favorably to the negative framing of the trustworthy physician. CONCLUSIONS: Trusted sources should use positive framing to foster vaccination acceptance. However, in a situation of heightened fears, a negative framing-attracting more attention to the risks-might be more effective. HIGHLIGHTS: How health workers frame their communication about a vaccine's probability of adverse side effects plays an important role in people's intentions to be vaccinated.In 4 experiments, we manipulated the trustworthiness of a physician and how the physician framed the risk of adverse side effects of a COVID vaccine.Positive framing given by a trustworthy physician promoted vaccination intention but had null effect or did backfire when given by an untrustworthy physician.The effect occurred over and above participants' attitude toward the health care system, risk perceptions, and beliefs in COVID misinformation.