Tonsillar Metastasis of Hepatocellular Carcinoma: A Case Report and Review of the Literature.

A 63-year-old male with stage IV hepatocellular carcinoma (HCC), accompanied by lung and adrenal metastases, presented with oral bleeding. Physical examination disclosed bleeding from the tonsillar mass. A head and neck computed tomography identified a 2.4 cm enhancing lesion in the right anterior ethmoidal sinus, extending to the nasal region and medial orbit. Tonsillar mass biopsy confirmed HCC metastasis, immunopositive for Hepatocyte Paraffin 1 (HepPar1) and Arginase. He was treated with local radiotherapy (30 fractions). The unique presentation of severe bleeding from a tonsillar biopsy-proven HCC metastatic lesion underscores the rarity of head and neck involvement. Extrahepatic metastasis, particularly to the head and neck area likely due to hematogenous spread, may be a major independent predictor of poor outcomes in HCC patients. Local radiotherapy to achieve local hemostasis and reduce tumor bulk should be considered. In patients with known HCC having new oropharyngeal symptoms, HCC metastasis should be considered for a timely diagnosis. Despite its rarity, this manifestation signifies an unfavorable prognosis, reinforcing the imperative for a multidisciplinary approach to enhance therapeutic outcomes in these complex scenarios.

Blastoid Mantle Cell Lymphoma Presenting as an Oropharyngeal Mass.

Blastoid mantle cell lymphoma (MCL) is an extremely rare neoplasm with a dismal prognosis. MCL with an initial presentation in the oral cavity has been rarely reported. This report describes a 75-year-old male who presented with an oropharyngeal mass causing dysphonia and intermittent hypoxia. A biopsy and immunophenotyping confirmed MCL, favoring the blastoid variant. Imaging showed a 4.2 cm left oropharyngeal polypoid mass with extensive lymphadenopathy. His prognosis was considered unfavorable with elevated Ki-67 index, blastoid morphology, and p53 positivity of malignant cells. There was no central nervous system involvement. He received palliative radiation, resulting in profound tumor reduction and resolution of symptoms. An intensive chemoimmunotherapy was not deemed beneficial due to age, comorbidities, absence of TP53 mutation, and a personal preference for a less aggressive treatment. This case highlights the importance of risk-adapted and personalized management approaches in a very unique presentation of blastoid MCL.

Reversible Cerebral Vasoconstriction Syndrome Mimicking Eclampsia.

This report describes the case of an 18-year-old Micronesian pregnant woman at 32 weeks gestation, initially presumed to have eclampsia but later diagnosed with reversible cerebral vasoconstriction syndrome (RCVS). She presented with seizures, altered mental status, nystagmus, lower extremity weakness, and absent reflexes. An extensive workup ruled out infectious and autoimmune causes, but a computed tomography angiogram (CTA) revealed severe cerebral vasoconstriction. Treatment included levetiracetam, intravenous magnesium, and nimodipine. The case highlights the challenge of differentiating RCVS from eclampsia in the postpartum period, emphasizing the importance of considering alternative diagnoses and brain CTA when RCVS is suspected, with calcium channel blockers potentially contributing to favorable neurological outcomes.

Burden of depressive disorders in Vietnam from 1990 to 2019: A secondary analysis of the Global Burden of Disease Study 2019.

Depressive disorders are among the leading causes of disability globally. However, information on the burden of depressive disorders in Vietnam is limited. We aimed to analyse the burden of depressive disorders in Vietnam from 1990 to 2019. Using data from the Global Burden of Disease Study 2019, prevalence and disability-adjusted life-years (DALYs) were used as indicators to analyse the burden of depressive disorders by age and sex. In 2019 in Vietnam, depressive disorders comprised 2629.1 thousand (95% uncertainty interval (UI): 2233.3-3155.9) estimated cases and 380.6 thousand (95% UI: 258.9-533.8) estimated DALYs. The crude prevalence rate of depressive disorders was higher among females than among males. The DALYs of depressive disorder accounted for a higher percentage of the total all-cause DALYs in the 10-64-year age group than in other age groups. Major depressive disorder was the largest contributor to the burden of depressive disorders. From 1990 to 2019, the crude prevalence and DALY rates per 100 000 population due to depressive disorders increased significantly, whereas age-standardised rates of prevalence and DALYs decreased significantly; the respective average annual percent changes were 0.88% (95% confidence interval: 0.87 to 0.89), 0.68% (0.66 to 0.70), -0.20% (-0.21 to -0.19), and -0.27% (-0.28 to -0.25). Although the age-standardised prevalence rate was lower than that seen globally, depressive disorders were considerable mental health issues in Vietnam. This study will help governments and policymakers to establish appropriate strategies to reduce the burden of these disorders by identifying the priority areas and individuals.

Diagnostic challenges of the idiopathic plasmacytic lymphadenopathy (IPL) subtype of idiopathic multicentric Castleman disease (iMCD): Factors to differentiate from IgG4-related disease.

AIMS AND METHODS: Idiopathic multicentric Castleman disease (iMCD) is currently considered to be classified into three clinical subtypes, including idiopathic plasmacytic lymphadenopathy (IPL), thrombocytopaenia, anasarca, fever, reticulin fibrosis/renal dysfunction, organomegaly (TAFRO) and not otherwise specified (NOS). Among the three, iMCD-IPL closely mimics IgG4-related disease (IgG4-RD). In diagnosing IgG4-RD, it is sometimes challenging to distinguish iMCD-IPL patients that also meet the histological diagnostic criteria for IgG4-RD. In this study, we focused on the number of IgG4-positive cells in the lymph nodes and analysed the relationship with laboratory findings to distinguish iMCD-IPL from IgG4-RD. Thirty-nine patients with iMCD-IPL and 22 patients with IgG4-RD were included. RESULTS: Among the cases considered to be iMCD-IPL, 33.3% (13/39) cases also met the histological diagnostic criteria for IgG4-RD and serum IgG4 levels were not different between the two groups. However, the serum IgG4/IgG ratio was significantly higher in IgG4-RD, with a cut-off value of 19.0%. Additionally, a significant positive correlation between serum IgG levels and the number of IgG4-positive cells was observed in iMCD-IPL (p=0.001). The serum IgG cut-off value for distinguishing iMCD-IPL meeting histological criteria for IgG4-RD from other iMCD-IPL was 5381 mg/dL. CONCLUSIONS: iMCD-IPL cases with high serum IgG levels (>5000 mg/dL) were likely to meet the diagnostic criteria for IgG4-RD because of the numerous IgG4-positive cells observed. A combination of clinical presentations, laboratory values including the serum IgG4/IgG ratios and histological analysis is crucial for diagnosis of IgG4-RD and iMCD-IPL.

Analysis of Notch1 protein expression in methotrexate-associated lymphoproliferative disorders.

Methotrexate (MTX)-associated lymphoproliferative disorder (MTX-LPD) is a lymphoproliferative disorder in patients treated with MTX. The mechanism of pathogenesis is still elusive, but it is thought to be a complex interplay of factors, such as underlying autoimmune disease activity, MTX use, Epstein-Barr virus infection, and aging. The NOTCH genes encode receptors for a signaling pathway that regulates various fundamental cellular processes, such as proliferation and differentiation during embryonic development. Mutations of NOTCH1 have been reported in B-cell tumors, including chronic lymphocytic leukemia/lymphoma, mantle cell lymphoma, and diffuse large B-cell lymphoma (DLBCL). Recently, it has also been reported that NOTCH1 mutations are found in post-transplant lymphoproliferative disorders, and in CD20-positive cells in angioimmunoblastic T-cell lymphoma, which might be associated with lymphomagenesis in immunodeficiency. In this study, to investigate the association of NOTCH1 in the pathogenesis of MTX-LPD, we evaluated protein expression of Notch1 in nuclei immunohistochemically in MTX-LPD cases [histologically DLBCL-type (n = 24) and classical Hodgkin lymphoma (CHL)-type (n = 24)] and de novo lymphoma cases [DLBCL (n = 19) and CHL (n = 15)]. The results showed that among MTX-LPD cases, the expression of Notch1 protein was significantly higher in the DLBCL type than in the CHL type (P < 0.001). In addition, among DLBCL morphology cases, expression of Notch1 tended to be higher in MTX-LPD than in the de novo group; however this difference was not significant (P = 0.0605). The results showed that NOTCH1 may be involved in the proliferation and tumorigenesis of B cells under the use of MTX. Further research, including genetic studies, is necessary.

Long-term trends in mortality from adverse effects of medical treatment in older populations in the United States from 1990 to 2019.

BACKGROUND: Adverse Effects of Medical Treatment (AEMT) refer to unintended harm caused by medical care and are a significant public health concern. OBJECTIVE: This study utilizes the Global Burden of Disease database to investigate AEMT mortality trends among older adults in the United States from 1990 to 2019, focusing on crude mortality rates and age-standardized mortality rate trends by age group and sex. METHODS: The study employs cause-of-death ensemble modeling and statistical analysis to examine crude and age-standardized mortality rates (ASRs) for AEMT in older age groups and identify trends in mortality due to AEMTs in those over 65 years of age in the United States. Trends in the ASR of AEMT were analyzed using the Joinpoint regression model. RESULTS: AEMT mortality rates increased among older adults from 2012 to 2019, with the highest increase observed in the 95 years or older age group. Significant differences were noted in AEMT mortality rates between older men and women, with older men having higher rates and showing an upward trend, while rates among older women decreased from 1990 to 2019. CONCLUSION: The study highlights an overall increase in ASR related to AEMT among older adults in the United States, with men shown to have a greater susceptibility to death from AEMT. Increased attention toward the detrimental impact of AEMT on our aging population, particularly for men, in conjunction with reinforcement of health policies and education, is warranted.

Cliff diving leading to commotio cordis in a patient with Ebstein's anomaly.

In this case report, we describe a 23-year-old male with Ebstein's anomaly who experienced out-of-hospital cardiac arrest due to commotio cordis following cliff diving. The patient previously underwent a Cone procedure and re-do reduction tricuspid valvuloplasty. Comprehensive investigations revealed no new ischemic events or structural abnormalities. He received an implantable cardioverter-defibrillator during an uneventful outpatient visit. This is the first reported case of commotio cordis in a patient with Ebstein's anomaly, suggesting a potential increased risk in individuals with congenital heart diseases. This highlights the significance of tertiary prevention in such cases. Learning objective: Through this case, readers may be able to review the incidence and electrical abnormalities leading to sudden cardiac death in patients with commotio cordis, the clinical presentation and mechanism of injury, and the current consensus regarding the management of commotio cordis.

Eosinophilic myocarditis: systematic review.

OBJECTIVE: In clinical practice, patients with eosinophilic myocarditis (EM) may forgo the gold standard diagnostic procedure, endomyocardial biopsy (EMB), although it is highly recommended in guidelines. This systematic review aims to summarise current approaches in diagnosing and treating EM with a particular emphasis on the utilisation and value of alternative diagnostic methods. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, we searched MEDLINE and EMBASE for all peer-reviewed articles using the keywords "eosinophilic myocarditis" from their inception to 10 September 2022. RESULTS: We included 239 articles, including 8 observational studies and 274 cases, in this review. The median patient age was 45 years. Initial presentations were non-specific, including dyspnoea (50.0%) and chest pain (39.4%). The aetiologies of EM were variable with the most common being idiopathic (28.8%) and eosinophilic granulomatosis polyangiitis (19.3%); others included drug-induced (13.1%) and hypereosinophilic syndrome (12.8%). 82.4% received an EM diagnosis by EMB while 17.6% were diagnosed based on clinical reasoning and cardiac MRI (CMR). CMR-diagnosed patients exhibited a better risk profile at diagnosis, particularly higher left ventricular ejection fraction and less need for inotropic or mechanical circulatory supports. Glucocorticoids were the primary treatment with variability in dosages and regimens. CONCLUSION: EMB is the mainstay for diagnostic testing for EM. CMR is potentially helpful for screening in appropriate clinical scenarios. Regarding treatment, there is no consensus regarding the optimal dosage of corticosteroids. Large clinical trials are warranted to further explore the utility of CMR in the diagnosis of EM and steroid regimen in treating EM.

Defining optimal blood pressure control for pre-transplant end-stage renal disease patients: scoping review.

BACKGROUND: Strict blood pressure control is essential to prevent cardiovascular disease and is associated with decreased mortality. However, in patients with end-stage renal disease awaiting renal transplantation, the level of optimal blood pressure control is not yet defined. METHODS: Following the PRISMA Extension for Scoping Reviews, we searched MEDLINE and EMBASE for all peer-reviewed articles using keywords including 'end-stage renal disease', 'blood pressure', and 'pre-transplant' from their inception to 7 August 2022. RESULTS: Seven observational studies, including one population-based study, were included in the review. Most studies investigated factors associated with post-transplant graft failure or mortality. There was considerable heterogeneity in defining optimal pre-transplant blood pressure measurement frequency among studies (average of three measurements vs. single measurement). One study suggested that low pre-transplant diastolic blood pressure (<50 mmHg) was associated with lower odds of delayed graft failure and mortality. Two studies noted that pre-transplant hypertension, or clinical criteria of hypertension that were present prior to transplant, was associated with post-transplant adverse outcomes. In contrast, one study noted that pre-transplant sustained hypotension with mean blood pressure <80 mmHg, was associated with a higher frequency of delayed graft failure. CONCLUSION: This systematic review summarizes the current evidence regarding the relationship between pre-transplant blood pressure control and post-transplant outcomes in end-stage renal disease patients. While the results from the included studies are mixed, more stringent blood pressure control than currently practiced may be beneficial to decrease graft failure and mortality in this patient population.

Intravenous Iron for Heart Failure: Updated Systematic Review and Meta-Analysis.

While the administration of intravenous (IV) iron to those with heart failure has been implicated to be associated with a possible reduction in hospitalizations and improvement in symptoms, a recent large multicenter trial only showed modest benefits in reducing hospitalization, necessitating the updated systematic review. We conducted a systematic review and meta-analysis, searching the MEDLINE and EMBASE database until January 9, 2023. Outcomes included total heart failure hospitalizations, first heart failure hospitalization, six-minute walk test (6MWT) distance, and incidence of infection. There were 13 studies with 3410 participants (1,790 with IV iron). Pooled analysis that reported the incidence of cardiovascular death showed that patients with IV iron did not have significantly lower odds of cardiovascular death or first heart failure hospitalization. In contrast, those who received IV iron had significantly lower total heart failure hospitalization (pooled odds ratio (OR) 0.63, 95% confidence interval (CI) 0.44-0.90, I2 59.0%, P = .017) and a composite of cardiovascular death and first heart failure hospitalization (pooled OR 0.55, 95% CI 0.47-0.64, I2 0%, P = .656). While the efficacy is modest, IV iron therapy could be associated with reduced hospitalization for heart failure without significant adverse events.

Factors Associated with Favorable Outcomes in Cardiac Arrest and Target Temperature Management.

Current guidelines strongly recommend providing targeted temperature management (TTM) after cardiac arrest, but hypothalamic dysregulation may confound TTM's impact on a patient's ultimate outcome. Although time to reach target temperature has largely been viewed as a process measure for TTM protocols, the difference between initial presenting temperature and target temperature (Δ-temperature) may be a potential surrogate marker of hypothalamic dysregulation. We performed a retrospective observational study to explore whether Δ-temperature was associated with neurologic outcomes and mortality. We included 86 patients (53 with out-of-hospital cardiac arrest [OHCA] and 33 with in-hospital cardiac arrest [IHCA]) in our analysis; more than half of the patients were cooled to 33°C (56.9% in OHCA and 57.6% in IHCA). In univariate logistic regression analysis, Δ-temperature alone did not appear to be statistically associated with mortality or neurologic outcomes regardless of target temperature. In exploratory analysis, longer time from TTM initiation-to-target was associated with worse neurological outcomes in the 33°C target (odds ratio = 0.996, 95% confidence interval = 0.992-1.000). Further research investigating the impact of hypothalamic dysregulation and Δ-temperature as well as the rate of cooling may be warranted to elucidate additional factors contributing to outcomes after cardiac arrest. In addition, our study population was noted to have a higher proportion of Asians and Native Hawaiians/Pacific Islanders, with a potential disparity in outcomes. Future studies may be warranted to ensure generalizability of TTM protocols and findings across populations.

Clinical Characteristics of Retroperitoneal Fibrosis Patients at a Tertiary Hospital in Japan.

Retroperitoneal fibrosis (RPF) is a rare cause of hydronephrosis and progressive renal dysfunction with unidentified origin. RPF is categorized into idiopathic RPF with/without immunoglobulin G4 (IgG4)-related disease (IgG4-RD), and secondary RPF. Identifying the underlying cause is challenging and often associated with delayed diagnosis or therapeutic interventions. We investigated RPF's clinical characteristics based on different etiologies and factors that may help distinguish the underlying causes. We analyzed the cases of 49 patients with RPF that was radiographically diagnosed at our institution (2008-2022). The cohort was 77.6% males; 75.5% had idiopathic RPF and 24.5% had secondary RPF. Among the idiopathic patients, 54.1% had IgG4-RD. The patients were likely to have abdominal pain, lower back pain/lumbago, and constitutional symptoms including generalized fatigue and fever. The idiopathic patients were likely to have higher serum IgG4 and IgG levels and lower serum C3 levels compared to secondary RPF. The IgG4-RPF patients were likely to have higher serum IgG4 levels and lower serum C-reactive protein, ferritin, and C3 levels compared to the idiopathic RPF patients without IgG4-RD. These findings might reflect underlying systemic inflammatory responses. Comprehensive laboratory testing, including serum inflammatory markers and immunological panels, is recommended for radiologically diagnosed RPF patients.

The risk of new heart failure associated with protease inhibitor: Systematic scoping review.

BACKGROUND: Protease inhibitors (PIs) have contributed to the long-term survival of persons with human immunodeficiency virus (PHIV). While there is a concern linking protease inhibitors to an increased risk of heart failure (HF), the evidence linking protease inhibitors and heart failure has been uncertain. METHODS: Following the PRISMA Extension for Scoping Reviews, we searched MEDLINE and EMBASE for peer-reviewed articles using keywords including "protease inhibitor," "heart failure," and "human immunodeficiency virus" from their inception to December 21, 2022. RESULTS: Five articles, including three observational studies and two randomized controlled trials, were included in the review. While protease inhibitors seem to be associated with atherosclerotic cardiovascular disease through their effects on metabolic markers, there is scarce evidence suggesting a direct association between protease inhibitors and heart failure. Although one study showed a possible correlation between protease inhibitor use and lower left ventricular ejection fraction and increased heart failure admission, the results were subject to confounders, and participants had poor medication adherence. CONCLUSION: Although current data are conflicting, there could be an association between PIs and HF in PHIV. Future prospective studies are warranted to evaluate the incidence of heart failure stratified on the generation of PIs and with adjustment for other metabolic risk factors.

Safety and usefulness of nebulized liposomal amphotericin B: Systematic scoping review.

PURPOSE: Invasive fungal infections potentially result in fatal outcomes in immunocompromised hosts. Compared to intravenous administration, a nebulization therapy can achieve a high concentration of drug delivered in the respiratory tract, without a systematic absorption. We herein summarized the study findings on the safety and clinical utility of nebulized liposomal amphotericin B therapy. METHODS: According to the PRISMA Extension for Scoping Reviews, we performed a search on MEDLINE and EMBASE for articles with relevant keywords, including "inhaled liposomal amphotericin B″, "nebulized liposomal amphotericin B″, or "aerosolized liposomal amphotericin B″, from the inception of these databases to August 31, 2022. RESULTS: Of the 172 articles found, 27 articles, including 13 case reports, 11 observational studies, and 3 clinical trials, were selected. Generally, findings showed that nebulized liposomal amphotericin B treatment appeared to be safe and without severe adverse effects. We found an accumulated evidence for the safety, tolerability, and effectiveness of nebulized liposomal amphotericin B prophylaxis among lung transplantation recipients; however, a randomized controlled study has yet to be reported. Data on hemato-oncological patients are relatively scarce; however, a randomized controlled study suggested the prophylactic effect of nebulized liposomal amphotericin B on invasive pulmonary aspergillosis. Observational and randomized controlled studies to evaluate therapeutic efficacy of the nebulized liposomal amphotericin B therapy have not been performed. CONCLUSION: In conclusion, we found increasing evidence for the effectiveness of the inhalation therapy among patients after lung transplantation and with hemato-oncological diseases.

Bile Cast Nephropathy Because of Acute Liver Injury Associated With Selective Androgen Receptor Modulators.

Selective androgen receptor modulators (SARMs) are novel nonsteroidal agents abused for performance enhancement such as anabolic steroids. We report a case of a 27-year-old man who used 3 different SARMs and presented with progressive weakness. Initial laboratory testing showed kidney and liver injury with creatinine 4.8 mg/dL and total bilirubin 43.3 mg/dL. An extensive workup was negative for other causes, and the results of liver and kidney biopsies were consistent with bile cast nephropathy because of SARM-associated drug-induced liver injury. His organ functions improved with the cessation of SARMs and plasmapheresis. Providers need to recognize the extreme consequences of SARM use.

Are Patients with HHV-8 Associated Castleman Disease Successfully Treated with Rituximab at Risk of Subsequently Developing HHV-8 Negative (Idiopathic) Castleman Disease?

Introduction: Multicentric Castleman disease (MCD) is a lymphoproliferative disorder characterized by lymph node histopathology and systemic symptoms. To our knowledge, there are no descriptions in the literature of long-term outcomes of human herpesvirus-8 (HHV-8)-associated MCD. Case Description: We report a case of a 70-year-old male living with human immunodeficiency virus and a history of human herpesvirus-8 (HHV-8)-associated MCD. The patient reported having had low-grade fever for two weeks. Extensive workup revealed systemic lymphadenopathy without evidence of autoimmune disease or malignancy. Lymph node biopsy was consistent with HHV-8-negative idiopathic MCD (iMCD). The patient was subsequently scheduled for anti-interleukin-6 therapy. Discussion: The present case is the first report of probable development of iMCD after long-term follow-up for HHV-8-associated MCD. The case illustrates the possible long-term consequences of MCD, suggesting the necessity of further research on the pathogenesis of CD. Conclusion: Given the uncertainty in the long-term outcomes of HHV-8-associated MCD, periodic surveillance of patients with a history of HHV-8-associated MCD is warranted. Prospective nationwide cohort studies comparing characteristics of HHV-8-associated MCD and iMCD would bring further insights. LEARNING POINTS: This is the first case describing the probable development of HHV-8-negative idiopathic MCD after HHV-8-associated MCD.Little is known of long-term outcomes of HHV-8-associated MCD and idiopathic MCD, necessitating periodic surveillance.HHV-8-negative idiopathic MCD patients are treated with siltuximab, an interleukin-6 inhibitor, unlike patients with HHV-8-associated MCD, who benefit most from rituximab.