Clinical Characteristics, Treatment Patterns, and Outcomes of Patients With Locally Advanced/Metastatic Hepatocellular Carcinoma Treated at the Veterans Health Administration.

PURPOSE: This study retrospectively reviewed the outcomes of patients with advanced hepatocellular carcinoma (HCC) receiving atezolizumab with bevacizumab (A + B) therapy at the Veterans Health Administration (VHA). PATIENTS AND METHODS: Patients with advanced HCC who received first-line systemic therapy with A + B at the VHA between December 1, 2019, and March 1, 2022, were selected from electronic medical records (EMR) using ICD-9 and ICD-10 codes. Abstractors reviewed the EMR of the patients from their index date of A + B initiation until death or their last VHA visit, with the study period ending on January 31, 2023. The chi-square test was used to compare rates, and the Mann-Whitney test was used to compare medians. RESULTS: A total of 332 patients met the study criteria. The median age was 67 years; 99% were male, 63% were non-Hispanic Whites, 26% were Black, and 66% had an Eastern Cooperative Oncology Group performance status of ≥1. 84% had child Pugh score (CPS) class A, 16% had CPS classes B and C, 62% had a grade 2 albumin-bilirubin score, 56% had HCC caused by viral hepatitis, 80% had cirrhosis, and 67% had received prior local therapies. The 6-month progression-free survival (PFS) was 59%, while the 1-year PFS rate was 36%. Overall survival (OS) at 1-year was 52% in our study. CONCLUSION: In real world, despite having similar PFS as the phase III IMbrave 150 trial, our OS at 12 months was lower (52% vs. 67%) because our study included a higher proportion of elderly patients with moderate liver dysfunction and a 40% non-White. This study provided real-world outcomes that differed from the study population in a pivotal trial.

Left atrium decompression devices across the spectrum of ejection fraction in heart failure: an updated systematic review and meta-regression analysis.

BACKGROUND: In patients affected by heart failure (HF) with reduced ejection fraction (HFrEF), pharmacological treatments have been proven to alleviate symptoms and improve prognosis, while no treatment other than sodium-glucose co-transporter-2 inhibitors have demonstrated significant effects in HF with preserved ejection fraction (HFpEF). Left atrium decompression devices (LADd) have been recently investigated as a new interventional approach in patients with HFpEF. OBJECTIVES: To assess the efficacy of LADd on soft endpoints in HF patients across the spectrum of ejection fraction. METHODS: PubMed and Web of Science were searched without restrictions from inception to 28 May 2022 to identify valuable articles. The studies that met the inclusion criteria were analyzed. The prespecified main outcomes were the change from baseline in 6-min walking distance (6MWD), NYHA class and health-related quality of life (HRQoL). Secondary outcomes were reduction in HF hospitalizations, echocardiographic, and hemodynamic parameters. RESULTS: Eleven studies, with a total of 547 patients, were included. LADd significantly improved 6MWD by 43.95 m (95% CI 29.64-58.26 m), decreased NYHA class by 0.93 (95% CI 1.20-0.67), and improved HRQoL questionnaire by 20.45 points (95% CI 13.77-27.14) with better results for all outcomes in patients with lower EFs. CONCLUSION: The present meta-analysis suggests that LADd are favorable in improving 6MWD, NYHA class, and HRQoL in HF across a wide spectrum of ejection fraction, with better outcomes in patients with lower EFs. TRIAL REGISTRATION: CRD42022336077, URL: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=336077 .

European e-Delphi process to define expert consensus on electrochemotherapy treatment indications, procedural aspects, and quality indicators in melanoma.

BACKGROUND: Skin metastases are an important co-morbidity in melanoma. Despite broad adoption, electrochemotherapy implementation is hindered by a lack of treatment indications, uncertainty regarding procedural aspects, and the absence of quality indicators. An expert consensus may harmonize the approach among centres and facilitate comparison with other therapies. METHODS: An interdisciplinary panel was recruited for a three-round e-Delphi survey. A literature-based 113-item questionnaire was proposed to 160 professionals from 53 European centres. Participants rated each item for relevance and degree of agreement on a five-point Likert scale, and received anonymous controlled feedback to allow revision. The items that reached concordant agreement in two successive iterations were included in the final consensus list. In the third round, quality indicator benchmarks were defined using a real-time Delphi method. RESULTS: The initial working group included 122 respondents, of whom 100 (82 per cent) completed the first round, thus qualifying for inclusion in the expert panel (49 surgeons, 29 dermatologists, 15 medical oncologists, three radiotherapists, two nurse specialists, two clinician scientists). The completion rate was 97 per cent (97 of 100) and 93 per cent (90 of 97) in the second and third rounds respectively. The final consensus list included 54 statements with benchmarks (treatment indications, (37); procedural aspects, (1); quality indicators, (16)). CONCLUSION: An expert panel achieved consensus on the use of electrochemotherapy in melanoma, with a core set of statements providing general direction to electrochemotherapy users to refine indications, align clinical practices, and promote quality assurance programmes and local audits. The residual controversial topics set future research priorities to improve patient care.

Electrochemotherapy is an effective locoregional therapy for skin metastases from melanoma, a problem faced by almost half of patients with metastatic disease. The lack of comparative studies and the heterogeneity of its clinical application among centres make it challenging to support consistent, evidence-based recommendations. To address this unmet need, a three-round online survey was conducted to establish a consensus on treatment indications, standard operating procedures, and quality indicators. In the survey, a panel of 100 European melanoma experts agreed on 56 statements that can be used to improve patient selection, homogenize treatment application, and monitor outcomes.

Cutaneous side effects and types of dermatological reactions in metastatic melanoma patients treated by immunotherapies or targeted therapies: A retrospective single center study.

Immunotherapy and target therapy have revolutionized treatment of stage III/IV melanoma. Both treatments show a favorable toxicity profile even if cutaneous adverse events (AEs) are frequent (30%-40% of cases). This is a retrospective single center cohort study that included patients with stage IV or inoperable stage III metastatic melanoma (AJCC 8th) who received BRAFi + MEKi therapy or immunotherapy with Checkpoint inhibitors. All cutaneous AEs were ascertained by a dermatologist based on clinical and histological findings. The primary outcome was to provide a detailed clinical dermatological classification of cutaneous adverse events and an evaluation of the incidence of skin toxicity in the two arms of therapy (immunotherapy and target therapy). A total of 286 patients with stages III-IV metastatic melanoma were included: 146 received immunotherapy and 140 target therapy. In the immunotherapy cohort, 63 (43.1%) cutaneous reactions were observed while 33 skin reactions (23.6%) were identified in patients treated with target therapy. All the skin toxicities observed were grade I, excepted four cases: an erythema multiforme-like eruption, a grade III psoriasis and two grade III maculopapular rashes. Immunotherapy in older age resulted statistically related to skin toxicities (p = 0.011), meanly in metastatic setting (p = 0.011). Cumulative incidence of skin toxicities was 65.63% in immunotherapy cohort (p = 0.001). Also multivariate logistic regression shows a significant association between skin adverse events and immunotherapy (odds ratio [OR] = 0.50; 95% confidence interval [CI]: 0.29-0.85, p: 0.01) and between cutaneous AEs and metastatic setting (OR = 1.97; 95% CI: 1.04-3.74, p: 0.04). We have also shown that as the age of initiation of therapy increases the probability of developing skin toxicity grows. However, stratifying by type of therapies the effect of age persists only in immunotherapy (OD: 1.04; CI: 1.01-1.06; p: 0.04) while for target therapy age does not affect the onset of skin toxicity (OD 1.01; CI 0.98-1.04; p = 0.42). No differences were shown between patients on target therapy and immunotherapy regarding gender. Patients were also evaluated regarding concomitant therapies and seems that Levotyroxine may be involved in AEs during immunotherapy treatment. More studies are needed to deepen this aspect, also considering the medical history and diverse drug associations. Cutaneous adverse events are characterized by heterogeneous manifestations, are more often seen in patients on immunotherapy and dermatologists can play a crucial role in multidisciplinary care.

Coronavirus Disease among Workers in Food Processing, Food Manufacturing, and Agriculture Workplaces.

We describe coronavirus disease (COVID-19) among US food manufacturing and agriculture workers and provide updated information on meat and poultry processing workers. Among 742 food and agriculture workplaces in 30 states, 8,978 workers had confirmed COVID-19; 55 workers died. Racial and ethnic minority workers could be disproportionately affected by COVID-19.

Management of patients with atopic dermatitis undergoing systemic therapy during COVID-19 pandemic in Italy: Data from the DA-COVID-19 registry.

BACKGROUND: Few and small studies have described the management of immunomodulant/immunosuppressive therapies or phototherapy in atopic dermatitis (AD) patients during coronavirus disease 2019 (COVID-19) pandemic. METHODS: A national registry, named DA-COVID-19 and involving 35 Italian dermatology units, was established in order to evaluate the impact of COVID-19 pandemic on the management of adult AD patients treated with systemic immunomodulant/immunosuppressive medications or phototherapy. Demographic and clinical data were obtained at different timepoints by teledermatology during COVID-19 pandemic, when regular visits were not allowed due to sanitary restrictions. Disease severity was assessed by both physician- and patient-reported assessment scores evaluating itch intensity, sleep disturbances, and AD severity. RESULTS: A total of 1831 patients were included, with 1580/1831 (86.3%) continuing therapy during pandemic. Most patients were treated with dupilumab (86.1%, 1576/1831) that was interrupted in only 9.9% (156/1576) of cases, while systemic immunosuppressive compounds were more frequently withdrawn. Treatment interruption was due to decision of the patient, general practitioner, or dermatologist in 39.9% (114/286), 5.6% (16/286), and 30.1% (86/286) of cases, respectively. Fear of increased susceptibility to SARS-CoV-2 infection (24.8%, 71/286) was one of the main causes of interruption. Sixteen patients (0.9%) resulted positive to SARS-CoV-2 infection; 3 of them (0.2%) were hospitalized but no cases of COVID-related death occurred. CONCLUSIONS: Most AD patients continued systemic treatments during COVID pandemic and lockdown period, without high impact on disease control, particularly dupilumab-treated patients.

Prognostic and Predictive Biomarkers in Stage III Melanoma: Current Insights and Clinical Implications.

Melanoma is one of the most aggressive skin cancers. The 5-year survival rate of stage III melanoma patients ranges from 93% (IIIA) to 32% (IIID) with a high risk of recurrence after complete surgery. The introduction of target and immune therapies has dramatically improved the overall survival, but the identification of patients with a high risk of relapse who will benefit from adjuvant therapy and the determination of the best treatment choice remain crucial. Currently, patient prognosis is based on clinico-pathological features, highlighting the urgent need of predictive and prognostic markers to improve patient management. In recent years, many groups have focused their attention on identifying molecular biomarkers with prognostic and predictive potential. In this review, we examined the main candidate biomarkers reported in the literature.

Efficacy of dupilumab in prurigo nodularis in elderly patient.

Prurigo nodularis (PN) is a chronic disorder, affecting adults, with multiple nodules, typically on the limbs. The treatment is challenging, especially in elderly patients. An 85-year-old woman had developed in the last 3 years itch with nodular lesions and erythematous scaly patches and excoriations. The extension of the lesions was evaluated by body surface area (BSA) score and the patient's itch and disease-related sleep disorders by a Numeric Rating Scale (NRS) from 0 to 10. The Dermatology Life Quality Index (DLQI) and blood chemistry were performed before and during the therapy. At the baseline, the BSA score was 56%. Itch and disease-related sleep disorders were, respectively, NRS 10 and 5 and DLQI was 9. Total IgE count and lactate dehydrogenase were increased. After starting dupilumab, there was a rapid improvement, especially in pruritus. The patient reported the maximum peak of pruritus every day for 6 months. At this time, the itch almost disappeared and clinically only postinflammatory lesions appreciated, with normalization of the blood tests and without any side effects.

Clinical and Pathological Relevance of Drug-induced Vitiligo in Patients Treated for Metastatic Melanoma with Anti-PD1 or BRAF/MEK Inhibitors.

Current therapies for metastatic melanoma (anti-PD1 and BRAF/MEK inhibitors) can cause drug-induced vitiligo. The aim of this study is to dermatologically define and histologically characterize this new type of vitiligo, and assess the clinical course of the disease. Fourteen patients with metastatic melanoma treated with immune or targeted therapy were included in a dataset evaluating clinical data, vitiligo description and histopathological features. Vitiligo-like lesions occurred after a mean of 7.5 months from the start of the therapies (range 1-42 months), with a prevalence of the non-segmental variant (71.4%). Fifty percent of patients showed a clinical response (4 complete response and 3 partial response), 35.7% had stable disease, and one patient died after disease progression. Median survival from the start of the therapies was 32.5 months. Drug-induced vitiligo can be related to both immune and targeted therapies, is associated with a favourable prognosis, and has clinical characteristics different from the classical form.

BRAFi/MEKi in patients with metastatic melanoma: predictive factors of complete response.

AIM: A survival benefit was demonstrated by dabrafenib + trametinib for metastatic BRAF-mutated melanoma patients. Best response is a strong prognostic marker for survival. PATIENTS & METHODS: The specific features associated with complete response (CR) were evaluated. RESULTS: A total of 15/66 patients achieved CR. Median size of lesions was 3 cm (range: 0.5-10). Using that value as cut-off, the CR rate was 39.3% in patients with smaller lesions and 10.5% in patients with bigger size (p = 0.006). The clinical features associated with CR were the number of metastatic sites and the largest diameter of the biggest metastatic site. CONCLUSION: The number of the metastases and the diameter of the largest metastatic site are associated with a higher CR rate.

Identification of Risk Factors for Multiple Non-Melanoma Skin Cancers in Italian Kidney Transplant Recipients.

Background and objectives: Non-melanoma skin cancers (NMSCs) represent the most frequently encountered malignancy in organ transplant recipients and their incidence increases proportionally to the duration of immunosuppression. Furthermore, patients of this group often develop multiple and more aggressive cancers and, to date, risk factors for the development of multiple NMSCs have not been yet established. The present study aimed to identify risk factors for multiple NMSCs in a cohort of Italian kidney transplant recipients (KTRs). Materials and Methods: We consecutively included all KTRs referring to two post-transplant outpatient clinics of North-Western Italy between 2001 and 2017. In this cohort, we evaluated different clinical (endogenous and exogenous) risk factors in order to establish their correlation with NMSCs. Results: 518 KTRs were included, of which 148 (28.6%) developed keratinocyte cancers, with a single tumor in 77 subjects, two skin cancers in 31 patients, 3 in 21 patients, whereas at least 4 NMSCs developed in 19 KTRs. We observed an increased risk of the development of cutaneous neoplasms for the male gender, old age at transplantation (>50 years), light phototype, solar lentigo, history of sunburns, or chronic actinic damage. Considering patients affected by multiple keratinocyte neoplasms, we observed a significant association of actinic damage and solar lentigo with an increased risk of NMSCs; their significance was confirmed even at the multivariable model. Conclusions: Our results confirm the role played by chronic cutaneous actinic damage in carcinogenesis on KTRs and highlight the significance of individualized periodic dermatological screening.

Mogamulizumab versus vorinostat in previously treated cutaneous T-cell lymphoma (MAVORIC): an international, open-label, randomised, controlled phase 3 trial.

BACKGROUND: Cutaneous T-cell lymphomas are rare non-Hodgkin lymphomas with substantial morbidity and mortality in advanced disease stages. We compared the efficacy of mogamulizumab, a novel monoclonal antibody directed against C-C chemokine receptor 4, with vorinostat in patients with previously treated cutaneous T-cell lymphoma. METHODS: In this open-label, international, phase 3, randomised controlled trial, we recruited patients with relapsed or refractory mycosis fungoides or Sézary syndrome at 61 medical centres in the USA, Denmark, France, Italy, Germany, the Netherlands, Spain, Switzerland, the UK, Japan, and Australia. Eligible patients were aged at least 18 years (in Japan, ≥20 years), had failed (for progression or toxicity as assessed by the principal investigator) at least one previous systemic therapy, and had an Eastern Cooperative Oncology Group performance score of 1 or less and adequate haematological, hepatic, and renal function. Patients were randomly assigned (1:1) using an interactive voice web response system to mogamulizumab (1·0 mg/kg intravenously on a weekly basis for the first 28-day cycle, then on days 1 and 15 of subsequent cycles) or vorinostat (400 mg daily). Stratification was by cutaneous T-cell lymphoma subtype (mycosis fungoides vs Sézary syndrome) and disease stage (IB-II vs III-IV). Since this study was open label, patients and investigators were not masked to treatment assignment. The primary endpoint was progression-free survival by investigator assessment in the intention-to-treat population. Patients who received one or more doses of study drug were included in the safety analyses. This study is ongoing, and enrolment is complete. This trial was registered with ClinicalTrials.gov, number NCT01728805. FINDINGS: Between Dec 12, 2012, and Jan 29, 2016, 372 eligible patients were randomly assigned to receive mogamulizumab (n=186) or vorinostat (n=186), comprising the intention-to-treat population. Two patients randomly assigned to mogamulizumab withdrew consent before receiving study treatment; thus, 370 patients were included in the safety population. Mogamulizumab therapy resulted in superior investigator-assessed progression-free survival compared with vorinostat therapy (median 7·7 months [95% CI 5·7-10·3] in the mogamulizumab group vs 3·1 months [2·9-4·1] in the vorinostat group; hazard ratio 0·53, 95% CI 0·41-0·69; stratified log-rank p<0·0001). Grade 3-4 adverse events of any cause were reported in 75 (41%) of 184 patients in the mogamulizumab group and 76 (41%) of 186 patients in the vorinostat group. The most common serious adverse events of any cause were pyrexia in eight (4%) patients and cellulitis in five (3%) patients in the mogamulizumab group; and cellulitis in six (3%) patients, pulmonary embolism in six (3%) patients, and sepsis in five (3%) patients in the vorinostat group. Two (67%) of three on-treatment deaths with mogamulizumab (due to sepsis and polymyositis) and three (33%) of nine on-treatment deaths with vorinostat (two due to pulmonary embolism and one due to bronchopneumonia) were considered treatment-related. INTERPRETATION: Mogamulizumab significantly prolonged progression-free survival compared with vorinostat, and could provide a new, effective treatment for patients with mycosis fungoides and, importantly, for Sézary syndrome, a subtype that represents a major therapeutic challenge in cutaneous T-cell lymphoma. FUNDING: Kyowa Kirin.

Sentinel lymph node biopsy versus observation in thick melanoma: A multicenter propensity score matching study.

The clinical value of sentinel lymph node (SLN) biopsy in thick melanoma patients (Breslow >4 mm) has not been sufficiently studied. The aim of the study is to evaluate whether SLN biopsy increases survival in patients with thick cutaneous melanoma, and, as a secondary objective, to investigate correlations between survival and lymph node status. We included 1,211 consecutive patients with thick melanomas (>4 mm) registered in the participating hospitals' melanoma databases between 1997 and 2015. Median follow-up was 40 months. Of these patients, 752 were matched into pairs by propensity scores based on sex, age, tumor location, histologic features of melanoma, year of diagnosis, hospital and adjuvant interferon therapy. The SLN biopsy vs. observation was associated with better DFS [adjusted hazard ratio (AHR), 0.74; 95% confidence interval (CI) 0.61-0.90); p = 0.002] and OS (AHR, 0.75; 95% CI, 0.60-0.94; p = 0.013) but not MSS (AHR, 0.84; 95% CI, 0.65-1.08; p = 0.165). SLN-negative patients had better 5- and 10-year MSS compared with SLN-positive patients (65.4 vs. 51.9% and 48.3 vs. 38.8%; p = 0.01, respectively). As a conclusion, SLN biopsy was associated with better DFS but not MSS in thick melanoma patients after adjustment for classic prognostic factors. SLN biopsy is useful for stratifying these patients into different prognostic groups.

Fatal Rocky Mountain Spotted Fever along the United States-Mexico Border, 2013-2016.

Rocky Mountain spotted fever (RMSF) is an emerging public health concern near the US-Mexico border, where it has resulted in thousands of cases and hundreds of deaths in the past decade. We identified 4 patients who had acquired RMSF in northern Mexico and subsequently died at US healthcare facilities. Two patients sought care in Mexico before being admitted to US-based hospitals. All patients initially had several nonspecific signs and symptoms, including fever, headache, nausea, vomiting, or myalgia, but deteriorated rapidly without receipt of a tetracycline-class antimicrobial drug. Each patient experienced respiratory failure late in illness. Although transborder cases are not common, early recognition and prompt initiation of appropriate treatment are vital for averting severe illness and death. Clinicians on both sides of the US-Mexico border should consider a diagnosis of RMSF for patients with rapidly progressing febrile illness and recent exposure in northern Mexico.

The infliximab biosimilar in the treatment of moderate to severe plaque psoriasis.

BACKGROUND: The infliximab originator's patent recently expired, leading to the production of biosimilar versions of the drug. The biosimilars' efficacy was not tested on patients with psoriasis but most regulatory authorities approved their use in psoriasis because of an extrapolation of data from studies conducted in other diseases. OBJECTIVE: We sought to describe the use of the infliximab biosimilar (Remsima; CT-P13) in patients with psoriasis. METHODS: Objective (Psoriasis Area and Severity Index) and subjective (visual analog pain scale) measurements of disease activity were collected in 2 cohorts of patients with moderate to severe plaque psoriasis: cohort 1 patients switched from the infliximab originator to the infliximab biosimilar; and cohort 2 patients were infliximab-naïve and started on the infliximab biosimilar. RESULTS: We observed no changes of Psoriasis Area and Severity Index and visual analog pain scale scores in 30 patients who switched from the infliximab originator to the biosimilar. Four of 5 infliximab-naïve patients who started infliximab biosimilar treatment achieved 75% improvement or better from baseline Psoriasis Area and Severity Index score at the end of the induction phase. LIMITATIONS: Number of patients and length of follow-up was limited. CONCLUSIONS: Patients with psoriasis taking infliximab originator treatment can switch to the infliximab biosimilar without experiencing a significant change in clinical response or additional adverse events. The use of the infliximab biosimilar could reduce the growing pressure on health care budgets.