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\"What are the origins of nationalism and why is it capable of arousing such intense emotions? In this major study, Azar Gat counters the prevailing fashionable theories according to which nations and nationalism are modern and contrived or 'invented'. He sweeps across history and around the globe to reveal that ethnicity has always been highly political and that nations and national states have existed since the beginning of statehood millennia ago. He traces the deep roots of ethnicity and nationalism in human nature, showing how culture fits into human evolution from as early as our aboriginal condition and, in conjunction with kinship, defines ethnicity and ethnic allegiances. From the rise of states and empires to the present day, this book sheds new light on the explosive nature of ethnicity and nationalism, as well as on their more liberating and altruistic roles in forging identity and solidarity\"-- Provided by publisher.

Lung cancer is worldwide the most common malignancy. Standard of care treatments for early-stage non-small-cell lung cancer (NSCLC) include surgery and adjuvant chemotherapy. However, these patients continue to have poor prognosis due to systemic or local relapse. Immunotherapy has been considered as a novel approach to improve survival in patients with early-stage NSCLC. Since immune checkpoint inhibitors have transformed the treatment of advanced NSCLC, there is a growing interest in the role of immunotherapy in early-stage NSCLC. In this review, we summarize reported and ongoing clinical trials of immunotherapy in both neoadjuvant and adjuvant settings. We also highlight unaddressed issues in this field of research, such as the predictive markers, the optimal combination therapy, and the need for adjuvant immunotherapy. More studies are needed to optimize the treatment regimen of immunotherapy in patients with early-stage NSCLC.

Immune checkpoint inhibitors (ICIs) have transformed the management of metastatic melanoma, providing durable survival benefits in a subset of patients. However, their use is associated with immune-related adverse events (irAEs), which may be unpredictable, severe, and occasionally fatal. We describe the case of a 77-year-old man with metastatic melanoma treated with nivolumab plus relatlimab (Opdualag), who achieved a marked antitumor response after seven treatment cycles. He subsequently developed fulminant late-onset myositis with multi-organ involvement, representing a particularly severe and atypical presentation. Despite timely recognition and aggressive immunosuppressive therapy, the clinical course was unfavorable, and the patient ultimately succumbed to these complications. To the best of our knowledge, this is the first published report of such a rare and fulminant multi-organ presentation of Opdualag-associated myositis. This report highlights the importance of vigilance for delayed and life-threatening irAEs and underscores the need for interdisciplinary collaboration and structured monitoring protocols as novel ICI combinations enter routine clinical practice.

Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine skin cancer with high metastatic potential. The impact of primary tumor location on survival outcomes for local and locally advanced disease remains incompletely understood, particularly regarding the influence of chronic sun exposure. To investigate the association between primary tumor location and overall survival in patients with local and locally advanced MCC, and explore the newer implications for treatment strategy. We conducted a multicenter retrospective analysis of Israeli patients with non-metastatic MCC with long-term follow-up. Overall survival was assessed by primary tumor location (head and neck versus other sites) using Kaplan-Meier analysis and Cox proportional hazards models adjusted for age, gender, and TNM stage. In total, 191 patients with local and locally advanced MCC were included, of whom 64 had head and neck MCC and 127 had MCC at other anatomical sites. Primary tumors located in the head and neck region were associated with significantly worse 5-year overall survival (51.6%) compared to other anatomical sites combined (65.2%, p = 0.025). In multivariate analysis, head and neck locations were associated with a significantly increased mortality risk (HR = 1.769, 95% CI: 1.104-2.835, p = 0.018) after controlling for age, gender, and TNM stage. Local and locally advanced head and neck MCC carries a significantly worse prognosis compared to MCC at other anatomical sites. Recent evidence of favorable responses to neoadjuvant immunotherapy in MCC, coupled with our findings, suggests that patients with head and neck disease may be appropriate candidates for this novel treatment approach. A paradigm shift toward neoadjuvant immunotherapy, especially for head and neck MCC, warrants serious consideration.

Many different types of cancer can be treated with immunotherapy drugs called immune checkpoint inhibitors (ICIs). These drugs have altered the landscape of cancer treatment options since they function by triggering a stronger immune response to malignancy. As expected, ICIs’ modification of immune regulatory controls leads to a wide range of organ/gland-specific immune-related side effects. These adverse effects are uncommonly deadly and typically improve by discontinuing treatment or administering corticosteroid drugs. As a result of a number of factors—including a lack of specificity in the clinical presentation, the possibility of overlap with other cardiovascular and general medical illnesses, difficulties in diagnosis, and a general lack of awareness—the true incidence of ICI-associated myocarditis is likely underestimated. Currently, protocols for the surveillance, diagnosis, or treatment of this condition are unclear. Several questions remain unanswered, such as how to best screen for this rare toxin, what tests should be run on patients who are suspected of having it, how to treat myocarditis once it has developed, and who is at most risk. In this article, we provide a case study of ICI-associated myocarditis and explain its key characteristics and treatment options.

Non-melanoma skin cancers (NMSC) form the majority of skin cancers, with basal cell carcinoma (BCC) being the most common and cutaneous squamous cell carcinoma (cSCC) being second. Prolonged ultraviolet (UV) exposure, aging, male gender, and immunosuppression represent most of the causes of this category of diseases. BCCs and cSCCs both include different types of skin cancers, such as nodular or morpheaform BCC or flat cSCC. Locally advanced and metastatic NMSCs cannot be treated surgically; thus, systemic therapy (TKI and Immunotherapy) is needed. Interestingly, NMSCs are frequently linked to abnormal Hedgehog (HH) signaling which most systemic immunotherapies for these cancers are based upon. Of note, the first line therapies of BCC, sonidegib and vismodegib, are HH inhibitors. Programmed death receptor 1 antibody (PD-1) inhibitors such as cemiplimab, pembrolizumab, and nivolumab have been approved for the treatment of cSCC. Thus, this paper reviews the epidemiology, risk factors, clinical features, and treatment options for both BCC and cSCC.

The introduction of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment standards and significantly enhanced patient prognoses. However, the utilization of these groundbreaking therapies has led to the observation and reporting of various types of adverse events, commonly known as immune-related adverse events (irAEs). In the following article, we present four patients who encountered uncommon toxicities induced by ICIs. The first patient was a 59-year-old female diagnosed with stage 4 lung adenocarcinoma. She received immunotherapy (pembrolizumab) together with chemotherapy and subsequently developed autonomic neuropathy (AN). The next two patients also received chemo-immunotherapy (pembrolizumab) and were both 63-year-old males with stage 4 lung adenocarcinoma. One of the two experienced palmoplantar keratoderma, while the other presented with Reiter’s syndrome (urethritis, conjunctivitis and arthritis). The 4th patient, an 80-year-old male with stage 4 squamous cell carcinoma of the lung, received chemo-immunotherapy (pembrolizumab) and developed myasthenia gravis.

Background Merkel cell carcinoma (MCC) is a rare and aggressive malignancy of the skin, affecting predominantly the fair‐skinned older population exposed to high levels of ultraviolet light. Immune suppression is considered a significant risk factor. With the recent advances in the field of immunotherapy, the treatment paradigm for advanced MCC, traditionally based on chemotherapy, has largely shifted to anti‐PD‐L1 and PD‐1 agents such as avelumab and pembrolizumab, respectively. However, real‐world data remain sparse. The aim of this study was to assess real‐world evidence of the effectiveness of avelumab in a diverse group of patients with MCC in Israel. Methods The electronic databases of five university hospitals in Israel were searched for all consecutive patients with MCC treated with at least one dose of avelumab in 2018–2022. Data on baseline, disease‐related, treatment‐related, and outcome parameters were collected and analyzed. Results The cohort included 62 patients of whom 22% were immune‐suppressed. The overall response rate to avelumab was 59%. The median progression‐free survival was 8.1 months, and the median overall survival, 23.5 months, with no differences between immune‐competent and immune‐suppressed patients. Treatment was well tolerated; any‐grade toxicity developed in 34% of patients, and grade 3–4 toxicity, in 14%. Conclusions Avelumab was found to be effective and safe for the treatment of advanced MCC in a diverse group of patients, including some with immune suppression. Further studies are warranted to evaluate the optimal sequence and duration of treatment and to assess the potential role of avelumab for earlier stages of MCC. Assessment of the effectiveness of avelumab in a diverse group of patients with MCC in multi‐center real‐world evidence from Israel. Avelumab was found to be effective and safe in a diverse group of patients, including some with immune suppression.

Recent advancements in targeted therapies for non-small-cell lung cancer (NSCLC), specifically focusing on epidermal growth factor receptor (EGFR) mutations, have revolutionized treatment strategies. Osimertinib, an approved therapy for metastatic NSCLC with EGFR mutations, highlights remarkable efficacy but also harbors the potential for severe adverse events, whose rarity or lack of precedence may mask their criticality. This article delves into the exploration of adverse events linked to osimertinib, shedding light on a rare yet life-threatening occurrence: severe myelosuppression. A case study detailing a patient with EGFR-mutated NSCLC exhibiting a robust treatment response but experiencing severe myelosuppression following osimertinib initiation is presented. Immediate discontinuation of osimertinib alongside concurrent blood transfusions facilitated toxicity recovery, prompting a successful reduction in myelosuppression severity upon re-administration at a lowered dosage.

Background and Objectives: Colorectal cancer (CRC) ranks as the third most prevalent cancer globally and is the third leading cause of cancer-related deaths. In 2020 alone, there were over 1.9 million new cases of CRC and nearly 0.9 million deaths worldwide. The incidence and outcomes of CRC exhibit significant geographical and temporal variations, largely influenced by diverse risk factors among populations. Recognizing the prognostic factors and the presenting symptoms of CRC, a leading global cancer with high mortality, can enhance early detection and thereby improve clinical outcomes. Materials and Methods: This retrospective, observational study analyzed 724 CRC elderly patients aged 70 and over (median age 80, 53.17% male), treated at a single center. Data on demographics, clinical characteristics, and outcomes were collected. Overall survival was analyzed using Kaplan–Meier curves, with stratification based on tumor location, disease staging, lymph node involvement, and family history. Results: Our study encompassed all CRC cases treated with surgery and systemic therapies (chemotherapy or biological agents) from July 2002 to September 2020. We focused on comparing prognosis between left-sided and right-sided CRC, as well as rectal cancer. We found that left-sided CRC demonstrated a superior prognosis compared to rectal cancer (p = 0.0022). Furthermore, among patients with CRC, tumors originating in the rectum were associated with worse outcomes compared to those arising in both the right and left colon, regardless of disease stage (p = 0.0049). Additionally, a family history of CRC was associated with poorer prognosis, impacting both metastatic (p = 0.0022) and localized disease (p = 0.035). The main symptoms prompting patients to start an investigation of CRC were abdominal pain (31.49%), anemia (18.08%), rectal bleeding (hematochezia) (17.82%), change in bowel habits (9.94%), and weight loss (7.60%). Conclusions: This study provides valuable insights into the symptoms prompting initial investigation and the prognostic factors associated with CRC in an elderly population with varied characteristics. It underscores the need for increased vigilance in recognizing key symptoms and the importance of personalized treatment strategies tailored to these prognostic factors.