Estimation of the Clinical, Economic, and Social Burden of Stage IV Non-Small Cell Lung Cancer in Mexico.

INTRODUCTION: Lung cancer continues to be the leading cause of death among cancer patients worldwide. This study aimed to estimate the clinical, economic, and social burdens of stage IV non-small cell lung cancer (NSCLC) in private and public healthcare centers in Mexico, utilizing real-world evidence. METHODS: The study population included patients >18 years of age diagnosed with stage IV NSCLC who received cancer treatment at the Centro Médico Nacional Siglo XXI (IMSS), the Centro Médico Nacional "20 de Noviembre" (ISSSTE), the Mexican Institute of Respiratory Diseases (INER), and the Medical Center ABC (American British Cowdray) from 1 January 2019 to 31 December 2020. The analysis included evaluation of epidemiological data, treatment regimens, and clinical outcomes, and emphasized pharmacological and non-pharmacological treatments, including detailed follow-up investigations, as part of comprehensive clinical management. Additionally, the study assessed the social burden through variables such as working-age absenteeism and presenteeism and caregiver productivity loss, as well as economic burden, considering both clinical and social components, with costs adjusted to 2022 Mexican pesos (MXN) values. RESULTS: A total of 188 patients with metastatic NSCLC were studied. The main type of NSCLC tumor found in the sample was adenocarcinoma (81%). Treatment regimens included pharmacological treatments (78%), non-pharmacological treatments (25%), and palliative care (24%). Complications were present in 73% of the cohort, while 60% presented adverse events. Clinical management costs of up to MXN1,001,579 per patient in the public sector and MXN2,140,604 in the private sector were reported. It was estimated that working-age patients lose 84-335 days yearly due to absenteeism and presenteeism, while caregivers report a productivity loss equivalent to 13-30 days due to the management of NSCLC patients. These indirect costs of NSCLC contribute to the social burden. A working-age patient with stage IV disease is associated with an average indirect cost of MXN49,731-178,287 in public institutions, while in private institutions, the cost elevates to MXN438,103. CONCLUSIONS: This study highlights the substantial clinical, economic, and social burdens of stage IV NSCLC in Mexico, revealing significant disparities between public and private healthcare sectors. It underscores the urgent need for standardized practices and equitable care across all systems.

This study examined the effects of advanced lung cancer (stage IV non-small cell lung cancer [NSCLC]) on patients in Mexico, focusing on the health, financial, and caregiver burdens. Researchers studied adults over 18 years of age undergoing cancer treatment at four medical centers across Mexico, analyzing treatment costs and time lost due to illness. All costs were updated to 2022 Mexican pesos (MXN) values. Treating one patient for 1 year can cost up to MXN 1 million in public hospitals and more than MXN 2 million in private hospitals. Patients might lose about 84­335 days of work annually, with caregivers losing 13­30 days. These lost workdays significantly impact finances, costing approximately MXN50,000­178,000 per patient per year in public hospitals and MXN438,000 in private hospitals. The study concludes that understanding these costs can help create better treatment plans, improving patient care and reducing financial burdens. By aligning treatment strategies across public and private healthcare settings, patients could benefit from more consistent and effective care, potentially leading to better health outcomes and reducing the overall impact of the disease on their lives and the broader healthcare system.

Cancer of Unknown Primary: When Imaging, Pathology, and Molecular Biology Do Not Match.

Introduction: Cancers of unknown primary are aggressive and rare malignancies with a complex diagnosis and management. Here we present a case in which imaging, pathology, and molecular biology did not match for a specific tumor site and the importance of a multidisciplinary team for these complicated cases. Case Presentation: A man in his 70s with strong smoking history under workup for suspicion of metastatic lung cancer underwent lung mass biopsy. Immunohistochemical stains corresponded to hepatocellular/cholangiocarcinoma or germ cell tumor; however, dedicated liver and testicular studies including imaging and iscochrome 12p FISH were negative. Additionally, somatic variant profiling was not specific for any malignancy nor targetable variants. Given the pattern of disease, risk factors, and patient history, the patient received treatment for lung adenocarcinoma (carboplatin, pemetrexed, and pembrolizumab). The patient had a drastic improvement in dyspnea, weight gain, and was able to return to work. Conclusion: This report describes a case in which immunohistochemistry and molecular profiling did not identify the tissue of origin and highlights the importance of a multidisciplinary team to reach a diagnosis and guide treatment without delaying patient care in patients with these diagnoses.

Novel Radiological Brain Anomalies in a Patient with Congenital Muscular Dystrophy due to FKRP Mexican Founder Mutation c.1387A > G: Review of the Literature.

Mutations in the FKRP gene result in phenotypes with severe forms of congenital muscular dystrophies (CMD) and limb-girdle muscular dystrophies. We present a Mexican patient with a pathogenic homozygous mutation in the FKRP gene (c.1387A > G, p.Asn463Asp) and CMD with radiological brain anomalies as disseminated hyperintensity lesions and discrete generalized cortical atrophy. These findings have not been reported to the best of our knowledge in other patients with the same mutation. The mutation c.1387A > G, p.Asn463Asp in the FKRP gene has been described to have a founder effect in central Mexico, since all the patients described to date are of Hispanic origin. Therefore, we emphasize studying mutations in the FKRP gene in Hispanic pediatric patients with clinical suspicion of CMD. Clinical and molecular diagnosis of specific CMD subtypes is needed to help clarify the prognosis, management, and genetic counseling to the patient and families.

Recurrent/Metastatic Nasopharyngeal Carcinoma Treatment from Present to Future: Where Are We and Where Are We Heading?

OPINION STATEMENT: Nasopharyngeal carcinoma (NPC) is distinct in its anatomic location and biology from other epithelial head and neck cancer (HNC). There are 3 WHO subtypes, which considers the presence of Epstein-Barr virus (EBV) and other histopathology features. Despite the survival benefit obtained from modern treatment modalities and techniques specifically in the local and locally advanced setting, a number of patients with this disease will recur and subsequently die of distant metastasis, locoregional relapse, or both. In the recurrent setting, the ideal therapy approach continues to be a topic of discussion and current recommendations are platinum-based combination chemotherapy. Phase III clinical trials which led to the approval of pembrolizumab or nivolumab for head and neck squamous cell carcinoma (HNSCC) specifically excluded NPC. No immune checkpoint inhibitor therapy, to date, has been approved by the FDA to treat NPC although the National Comprehensive Cancer Network (NCCN) recommendations do include use of these agents. Hence, this remains the major challenge for treatment options. Nasopharyngeal carcinoma is challenging as it is really 3 different diseases, and much research is required to determine best options and sequencing of those options. This article is going to address the data to date and discuss ongoing research in EBV + and EBV - inoperable recurrent/metastatic NPC patients.

Early Stage and Locally Advanced Nasopharyngeal Carcinoma Treatment from Present to Future: Where Are We and Where Are We Going?

OPINION STATEMENT: Nasopharyngeal carcinoma (NPC) is a rare malignancy, endemic in China, that is commonly diagnosed in locally advanced scenarios. Its pathogenesis is strongly associated with Epstein-Barr virus (EBV), an infection for which measuring EBV plasma DNA levels has helped as a prognostic factor guiding treatment options, including a stronger treatment in those with high titers. Additionally, tobacco and alcohol are often implicated in EBV-negative patients. The local disease is treated with radiotherapy alone, preferentially intensity modulated radiotherapy. For locally advanced disease, the backbone treatment is concurrent chemoradiotherapy with the ongoing research dilemma being adding adjuvant chemotherapy or induction chemotherapy. The ongoing research is focused not only on identifying patients that will benefit from adjuvant or induction chemotherapy, but also on identifying the best chemotherapeutic regimen, regimen alternatives to diminish toxicity, the role that immune checkpoint inhibitors play, and the use of molecularly guided treatment targeting patients with NPC whether driven by EBV or tobacco and alcohol. Knowing the precise oncogenesis of NPC not only offers a better understanding of the role that EBV plays in this tumor but also helps create targeted therapies that could potentially block important pathways such as the NF-κB pathway. Much is yet to be done, but the prognosis and management of NPC patients have changed drastically, offering precise treatment methods and excellent control of the disease, even in locally advanced scenarios.

Epirubicin, cisplatin plus ifosfamide versus standard chemotherapeutic regimens for advanced/unresectable primary thoracic sarcomas.

PURPOSE: Thoracic sarcomas are rare malignancies, with limited data for unresectable/advanced scenarios. Our goal is to provide insights of a three-drug chemotherapy regimen improving patient survival compared to standard regimens. METHODS: Retrospective cohort analysis of patients diagnosed with unresectable/advanced primary thoracic sarcoma divided between primary pulmonary sarcomas (PPS) and chest wall sarcomas (CWS) comparing chemotherapeutical regimens efficacy. Not true soft tissue sarcomas (STS) for PPS were excluded from the analysis. Univariate and multivariate analysis performed via Cox-regression model. Progression-free survival (PFS) and overall survival (OS) analysis via Kaplan-Meier with hazard ratio (HR) obtained via Mantel-Haenszel or log rank. RESULTS: 157 total cases were included, from which 50 cases were PPS and 107 cases CWS. For PPS, 4 cases were excluded from the analysis as they were not true STS. The most common histology was undifferentiated sarcomas, 63% of cases were treated with E/C/I and 37% with another regimen. The E/C/I regimen demonstrated a benefit for both OS (p = 0.020) and PFS (p = 0.010) when compared to any other regimen as well as when compared to non-platinum regimens (p = 0.016 and p = 0.001). Regarding CWS, the most common histology was synovial and undifferentiated sarcomas, 55.1% were treated with E/C/I and 44.9% treated with another regimen. The E/C/I regimen did not demonstrate a benefit for OS or PFS compared to any other regimen, neither when compared to other non-platinum regimens. However, a benefit was observed in favor of E/C/I when compared to other platinum regimens in both OS (p = 0.049) and PFS (0.015). Both analyses for PPS and CWS demonstrated a benefit in favor of cisplatin therapies compared to carboplatin in both OS and PFS. CONCLUSION: This study demonstrates that platinum therapy alone does not work, and that cisplatin must be the agent of choice and it's used in combination could increase treatment response. The E/C/I regimen demonstrated a in PPS but not for CWS, this is due do their rarity of PPS and that no standard treatment is established yet. The regimen proposed here could represent a possible new standard of treatment for PPS as long as it is validated in a prospective study.

Paraneoplastic Cerebellar Degeneration with Anti-CV2/CRMP5 Antibodies in Ovarian Cancer: Case Report and Review of the Literature.

Paraneoplastic neurological syndromes (PNS) are rare presentations of an underlying oncological disease and more unusual during an oncological disease. They most likely present in small-cell lung carcinomas and thymomas, but present in <1% of the gynecological neoplasms. Acknowledging the pathophysiology is essential for management, explaining its clinical presentation, and future research. We present a patient with an underlying gynecological cancer that during her disease developed a PNS with an unusual autoantibody (anti-CV2/CRMP5) mediating the disease. We report a case of a 62-year-old female diagnosed with ovarian cancer who in the course of her disease developed neurological symptoms associated with cerebellar degeneration. After ruling out differential diagnoses such as metastases, a PNS was suspected and studied, in which anti-CV2/CRMP5 antibodies were positive. With her clinical presentation, radiological features, autoantibody positivity on cerebrospinal fluid, and an underlying oncological disease, cerebellar degeneration was diagnosed. The pathophysiology of PNS is not fully understood; therefore, its diagnosis and management are complex. Diagnosis is based on clinical presentation and specific antibodies associated. Unfortunately, patients have a bad prognosis and diminished quality of life, and therefore a multidisciplinary approach is needed. It is important to mention that the presentation of PNS does not mandatorily appear before the diagnosis of cancer, and multiple cases have been reported in which patients with an underlying oncological disease develop these syndromes. As medical oncologists and neurologists, we must consider and study these syndromes as a possible etiology in cases with an underlying cancer who develop neurological symptoms in the course of their disease.

Immunization with neural-derived peptides increases neurogenesis in rats with chronic spinal cord injury.

AIMS: Immunization with neural-derived peptides (INDP) has demonstrated to be a promising therapy to achieve a regenerative effect in the chronic phase of the spinal cord injury (SCI). Nevertheless, INDP-induced neurogenic effects in the chronic stage of SCI have not been explored. METHODS AND RESULTS: In this study, we analyzed the effect of INDP on both motor and sensitive function recovery; afterward, we assessed neurogenesis and determined the production of cytokines (IL-4, IL-10, and TNF alpha) and neurotrophic factors (BDNF and GAP-43). During the chronic stage of SCI, rats subjected to INDP showed a significant increase in both motor and sensitive recovery when compared to the control group. Moreover, we found a significant increase in neurogenesis, mainly at the central canal and at both the dorsal and ventral horns of INDP-treated animals. Finally, INDP induced significant production of antiinflammatory and regeneration-associated proteins in the chronic stages of SCI. CONCLUSIONS: These findings suggest that INDP has a neurogenic effect that could improve motor and sensitive recovery in the chronic stage of SCI. Moreover, our results also envision the use of INDP as a possible therapeutic strategy for other trauma-related disorders like traumatic brain injury.

Use of a Combination Strategy to Improve Morphological and Functional Recovery in Rats With Chronic Spinal Cord Injury.

Immunization with neural derived peptides (INDP), as well as scar removal (SR) and the use of matrices with bone marrow-mesenchymal stem cells (MSCs), have been studied separately and proven to induce a functional and morphological improvement after spinal cord injury (SCI). Herein, we evaluated the therapeutic effects of INDP combined with SR and a fibrin glue matrix (FGM) with MSCs (FGM-MSCs), on motor recovery, axonal regeneration-associated molecules and cytokine expression, axonal regeneration (catecholaminergic and serotonergic fibers), and the induction of neurogenesis after a chronic SCI. For this purpose, female adult Sprague-Dawley rats were subjected to SCI, 60 days after lesion, rats were randomly distributed in four groups: (1) Rats immunized with complete Freund's adjuvant + PBS (vehicle; PBS-I); (2) Rats with SR+ FGM-MSCs; (3) Rats with SR+ INDP + FGM-MSCs; (4) Rats only with INDP. Afterwards, we evaluated motor recovery using the BBB locomotor test. Sixty days after the therapy, protein expression of TNFα, IL-4, IL-10, BDNF, and GAP-43 were evaluated using ELISA assay. The number of catecholaminergic and serotonergic fibers were also determined. Neurogenesis was evaluated through immunofluorescence. The results show that treatment with INDP alone significantly increased motor recovery, anti-inflammatory cytokines, regeneration-associated molecules, axonal regeneration, and neurogenesis when compared to the rest of the groups. Our findings suggest that the combination therapy (SR + INDP + FGM-MSCs) modifies the non-permissive microenvironment post SCI, but it is not capable of inducing an appropriate axonal regeneration or neurogenesis when compared to the treatment with INDP alone.

Acinetobacter baumannii Resistance: A Real Challenge for Clinicians.

Acinetobacter baumannii (named in honor of the American bacteriologists Paul and Linda Baumann) is a Gram-negative, multidrug-resistant (MDR) pathogen that causes nosocomial infections, especially in intensive care units (ICUs) and immunocompromised patients with central venous catheters. A. baumannii has developed a broad spectrum of antimicrobial resistance, associated with a higher mortality rate among infected patients compared with other non-baumannii species. In terms of clinical impact, resistant strains are associated with increases in both in-hospital length of stay and mortality. A. baumannii can cause a variety of infections; most involve the respiratory tract, especially ventilator-associated pneumonia, but bacteremia and skin wound infections have also been reported, the latter of which has been prominently observed in the context of war-related trauma. Cases of meningitis associated with A. baumannii have been documented. The most common risk factor for the acquisition of MDR A baumannii is previous antibiotic use, following by mechanical ventilation, length of ICU/hospital stay, severity of illness, and use of medical devices. Current efforts focus on addressing all the antimicrobial resistance mechanisms described in A. baumannii, with the objective of identifying the most promising therapeutic scheme. Bacteriophage- and artilysin-based therapeutic approaches have been described as effective, but further research into their clinical use is required.