Measured Steps: Navigating the Path of Oligoprogressive Lung Cancer with Targeted and Immunotherapies.

PURPOSE OF REVIEW: This review discusses the definitions, treatment modalities, management, future directions, and ongoing clinical trials of oligoprogressive disease in oncogene-driven and non-oncogene-driven NSCLC. RECENT FINDINGS: During the last decades, diagnostic and treatment modalities for oligometastatic NSCLC have advanced significantly, leading to improved survival. Additionally, our understanding of the tumor biology of oligoprogressive disease has expanded. However, despite the efforts of organizations, such as EORTC, ESTRO, and ASTRO proposing definitions for oligometastatic and oligoprogressive disease, heterogeneity in definitions persists in (ongoing) trials. Recognizing the significance of subclassification within oligoprogressive disease in NSCLC and the varying risks associated with subsequent metastatic spread, there is a call for tailored management strategies. A consensus on standardized criteria for the definition of oligoprogressive disease is urgently needed and will not only facilitate meaningful comparisons between studies but also pave the way for the development of personalized treatment plans that take into account the heterogeneous nature of oligoprogressive disease.

Trends in hospitalisations and inpatient mortality from acute myocardial infarction among patients with psoriatic arthritis: an analysis of nationwide inpatient sample 2004-2014.

OBJECTIVES: Psoriatic arthritis (PsA) is associated with increased cardiovascular morbidity and mortality. Higher disease activity has been associated with increased rates of mortality in PsA. The objectives of the study were to describe the trends for hospitalisations from acute myocardial infarction (AMI) amongst patients with underlying PsA. METHODS: All adult hospitalisations for AMI with and without PsA from 2004-2014 in the nationwide in-patient sample (NIS) database were captured. A propensity score-matching model was also developed for comparative outcome analysis and reduce the potential of selection bias. RESULTS: From 2004 to 2014, 4778 unmatched weighted hospitalisations were estimated for AMI with underlying PsA. Mean age for hospitalisations with AMI and PsA was lower (average age in years: 63.1±11.5 vs. 67.5±14.4; p-value <0.05), with a higher percentage being males (62.7% vs. 60.4%, p-value <0.05). When adjusted for confounding factors, overall mortality was found to be signi cantly lower in hospitalisations with PsA (2.21% vs. 5.8%, p-value <0.05). After propensity matching analyses, in-hospital mortality in PsA cohort continued to be signi cantly lower when compared to the matched cohort without PsA (1.79% vs. 5.71%, Odds ratio=0.3, p-value 0.002). CONCLUSIONS: The study suggests that overall rates of mortality in AMI with underlying PsA are lower compared to those without PsA. A decrease in cardiovascular mortality from AMI in PsA re ects that even though PsA is associated with an increased prevalence of cardiovascular risk factors, the trends in mortality are similar or even better than those for the general population.

Collapsing glomerulopathy in a young woman with APOL1 risk alleles following acute parvovirus B19 infection: a case report investigation.

BACKGROUND: Collapsing Glomerulopathy (CG), also known as the collapsing variant of Focal Segmental Glomerulosclerosis (FSGS), is distinct in both its clinical severity and its pathophysiologic characteristics from other forms of FSGS. This lesion occurs disproportionally in patients carrying two APOL1 risk alleles, and is the classic histologic lesion resulting from Human Immunodeficiency Virus (HIV) infection of podocytes. Other viral infections, including parvovirus B19, and drugs such as interferon that perturb the immune system, have also been associated with CG. Despite significant advances, explaining such genetic and immune/infectious associations with causative mechanisms and supporting evidence has proven challenging. CASE PRESENTATION: We report the case of a healthy (HIV-negative) pregnant 36 year-old Caribbean-American woman who presented with nephrotic syndrome and fetal demise in the setting of acute parvovirus B19 infection. A series of three renal biopsies and rapid clinical course showed progression from significant podocyte injury with mild light microscopy findings to classic viral-associated CG to ESRD in less than 3 months. Genetic analysis revealed two APOL1 G1 risk alleles. CONCLUSIONS: This is the first published case report of CG in the setting of acute parvovirus infection in a patient with two APOL1 risk allelles, and parvoviral proteins identified in renal epithelium on kidney biopsy. These findings support the causative role of parvovirus B19 infection in the development of CG on the background of APOL1 genetic risk.

Tumor Characteristics and Treatment Responsiveness in Pembrolizumab-Treated Non-Small Cell Lung Carcinoma.

Pembrolizumab, a widely used immune checkpoint inhibitor (ICI), has revolutionized the treatment of non-small cell lung cancer (NSCLC). Identifying unique tumor characteristics in patients likely to respond to pembrolizumab could help the clinical adjudication and development of a personalized therapeutic strategy. In this retrospective study, we reviewed the clinical data and pathological features of 84 NSCLC patients treated with pembrolizumab. We examined the correlation between the clinical and demographic characteristics and the tumor histopathologic features obtained before immunotherapy. The response to pembrolizumab therapy was evaluated via the Response Evaluation Criteria in Solid Tumors (RECIST). The clinical data and cancer tissue characteristics were assessed and compared among three groups according to the following RECIST: the responsive group (RG), the stable disease group (SD), and the progressive disease group (PD), where the RG comprised patients with either a complete response (CR) or a partial response (PR). The overall survival rate of the RG group was significantly higher than the SD and PD groups. In addition, the percentage of pre-treatment viable tumor cell content in the RG and SD groups was significantly higher. At the same time, the extracellular stroma proportion was significantly lower than that of the PD group. The number of tumor-infiltrating lymphocytes (TILs) in the RG group was significantly higher than in the PD group. There were no significant differences in tumor necrosis, the stroma composition, PD-L1 expression level (TPS 1-49% vs. ≥50%), and treatment response. In conclusion, our population of NSCLC patients who experienced positive treatment responses to pembrolizumab therapy had a better prognosis compared to patients with either SD or PD. Moreover, the relative proportions of viable tumor cells to tumor-associated lymphocytes were associated with responsiveness to treatment. It is expected that larger prospective clinical studies will further validate these findings.

Bispecific Antibodies in Lung Cancer: A State-of-the-Art Review.

Bispecific antibodies have emerged as a promising class of therapeutics in the field of oncology, offering an innovative approach to target cancer cells while sparing healthy tissues. These antibodies are designed to bind two different antigens, enabling them to bridge immune cells with cancer cells, resulting in enhanced tumor cell killing and improved treatment responses. This review article summarizes the current landscape of bispecific antibodies in lung cancer, including their mechanisms of action, clinical development, and potential applications in other solid tumor malignancies. Additionally, the challenges and opportunities associated with their use in the clinic are discussed, along with future directions for research and development in this exciting area of cancer immunotherapy.

Tumid Lupus Erythematosus and Systemic Lupus Erythematosus: A Report on Their Rare Coexistence.

Tumid lupus erythematosus (TLE) is a rare variant of cutaneous lupus erythematosus. Clinically, it lacks typical changes found in discoid lupus and antinuclear antibodies (ANA) levels are elevated in only 10% of the patients. Coexistent systemic lupus erythematosus (SLE) has been reported to be rare, and literature shows only a few case reports. We present a case of coexistent tumid lupus and SLE. We present a case of a 48-year-old Caucasian female who presented with chronic facial rash, photosensitivity, intermittent oral ulcers, joint pain with morning stiffness, and unintentional weight loss. Laboratory studies showed positive ANA at 1:640, elevated erythrocyte sedimentation rate, positive anticardiolipin immunoglobulin (Ig) G, anticardiolipin IgM, and anti-beta-2 glycoprotein IgM. Skin biopsy of the rash showed a superficial and deep dense lymphocytic infiltrate with mucin deposition, histopathology favoring tumid lupus. The patient was diagnosed with TLE with SLE and was started on hydroxychloroquine with improvement in her rash. Ultraviolet light and certain medications have been proven to play a role in the pathogenesis of tumid lupus. It usually responds to photoprotection, topical treatment, or oral antimalarial therapy.

A Case of Long-term Survival of 36 Months in the Setting of Extensive-disease Small-cell Lung Cancer.

Small-cell lung cancer (SCLC) is an extremely aggressive disease characterized by early regional spread and distant metastases. Patients with extensive-disease (ED) SCLC have a median survival rate of 8-11 months. Despite high response rates to initial therapy, relapses are frequent. Systemic therapy after the first-line failure remains vital in the treatment paradigm of SCLC. The National Comprehensive Cancer Network (NCCN) guidelines dictate that previously administered first-line chemotherapy can be used in relapses that occur after six months from the completion of initial therapy. For relapses within six months of initial therapy, sequential treatment with single agents is recommended. In this report, we discuss the case of a long-term SCLC survivor with an ED. The patient underwent several lines of chemotherapy and prophylactic cranial irradiation (PCI) and survived for 36 months.

Bronchiolitis obliterans organising pneumonia as an initial manifestation in a patient with systemic lupus erythematosus: a rare presentation.

Bronchiolitis obliterans organising pneumonia as an initial manifestation of systemic lupus erythematosus (SLE) is a rare and uncommon presentation. We describe a case of SLE presenting with shortness of breath, found to have pneumothorax, bilateral nodular infiltrates along with pleural effusions and pericardial effusion. Work-up suggested a diagnosis of active SLE with anaemia, thrombocytopenia, positive antinuclear antibodies (ANAs) and positive anti-double-stranded DNA. On retrospective review of patient records, from 8 years prior to presentation, lung biopsy histology consistent with bronchiolitis obliterans organising pneumonia with positive ANA serology was found, without any further autoimmune work-up. In our opinion, bronchiolitis obliterans organising pneumonia was the index presentation of SLE. Treatment with steroids and subsequent management with immunosuppressive therapy could have prevented subsequent hospitalisations. Prompt work-up for autoimmune diseases should be considered in patients with positive ANA and histological evidence of bronchiolitis obliterans organising pneumonia.