Cardiac toxicity of HER-2 targeting antibody-drug conjugates: overview and clinical implications.

Antibody-drug conjugates (ADCs) have recently emerged as a promising therapeutic option that combine the specificity of monoclonal antibodies and the cytotoxic effect of chemotherapy. With numerous ADCs approved and on the market, a particular concern of ADCs that target HER-2 has been their cardiac side effects, in view of the crucial role of HER-2 in cardiac development and physiology. While rarely toxic and generally safe, numerous publications have outlined the consistent association of trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd) with the development of cardiac toxicity. Despite not being clinically relevant in most cases, cardiac baseline evaluation, monitoring and early detection of cardiac adverse events remain pivotal with HER-2 targeting ADCs. This review aims to summarize and better characterize the complete cardiac toxicity profile of HER-2 ADCs, with the goal of improving clinical understanding of this adverse event, leading to better recognition, monitoring and management.

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Insights Into the Emerging Entity of HER2-Low Breast Cancer.

Human epidermal growth factor receptor 2 (HER2)-low breast cancer (BC) is a subtype of BC that has been recently recognized as a separate clinical entity with distinct clinical and molecular characteristics. It is defined by a low level of HER2 protein expression, which distinguishes it from other more aggressive BC subtypes. Early studies suggest that it may have a more favorable prognosis than HER2-positive BC, as it is less likely to spread to other parts of the body and may be more responsive to standard BC treatments such as chemotherapy, radiation therapy, and hormone therapy. Given the relative new emergence of HER2-low BC, there is still much to be learned about this subtype; ongoing research is focused on identifying the underlying genetic mutations that contribute to HER2-low BC as well as developing targeted therapies that can improve outcomes for patients with this disease. This review is aimed at summarizing the current clinical knowledge on HER2-low BC, with the aim of creating a better understanding of this entity and paving the way for potential interventions and a new standard of care.

Intensive Care Unit Admission After Spine Surgery: A Narrative Review.

INTRODUCTION: Intensive care unit (ICU) admissions constitute a substantial financial challenge for health care systems and patients and are linked to various potentially life-altering complications. A wide range of patient-related, surgical, and medical factors are associated with an increased risk of ICU admission following spine surgery. DISCUSSION: The most notable examples include lung, heart, and kidney disease, as well as estimated blood loss and length of surgery. Various scores that include the most significant patient- and procedure-related factors have been described to assess the risk associated with surgery for individual patients. To date, the fusion risk score and the American Society of Anesthesiologists score have been the most useful in predicting postoperative complications and admission to the ICU. However, other risk factors have also been implicated in ICU admission and length of stay. The current scores must further adapt by using the available evidence to fulfill their intended purpose. Moreover, a handful of measures have shown efficacy in decreasing ICU admission and length of stay, with their benefits still to be demonstrated by future research. CONCLUSION: This review underscores the risk factors predictive of ICU admission following spine surgery and will help surgeons and clinicians in patient stratification. However, future studies are needed to validate the role of protective measures in preventing ICU admissions and the significance of certain risk factors.

Antegrade vs Retrograde Intra-Medullary Nailing in Femoral Shaft Fractures: A Systematic Review and Meta-Analysis.

Objectives: Femoral shaft fractures are one of the most prevalent fractures found in clinical practice. Numerous operative and non-operative options are readily available for the treatment of such fractures with intra-medullary nailing being the gold standard. To date, no consensus has been reached favoring one approach over the other. Thus, this meta-analysis aims to compare the outcomes between an antegrade and retrograde intra-medullary nailing for the treatment of femoral shaft fractures. Methods: PubMed, Cochrane, Google Scholar (page 1-20), and Embase were searched till January 2024. The clinical outcomes evaluated were the incidence of adverse events, reoperations, hip and knee pain, and surgery-related parameters. Results: Higher rates of hip pain, and heterotopic ossification (p=0.0003, and p=0.0002 respectively) was observed with antegrade nailing. However, a higher rate of knee pain (p=0.02) was appreciated in retrograde nailing. There was no statistically significant difference in the remaining analyzed outcomes such as operative time, reoperation rate or other complications. Conclusion: Despite a higher rate of heterotopic ossification using the antegrade nailing technique, both the antegrade and retrograde nailing techniques yield overall similar outcomes. Therefore, the decision to choose one or the other should be based on patient-related factors, and the surgeon's experience and preference.

Untwining the intertwined: a comprehensive review on differentiating pathologies of the shoulder and spine.

Background: The anatomic interplay and overlap between the cervical spine and the shoulder constitutes a challenge for shoulder and spine surgeons, as symptoms of spine and shoulder pathologies are often similar and may lead to entity misdiagnosis. Methods: PubMed, Cochrane, and Google Scholar (page 1-20) searches were updated to October 2023 in search of the qualified papers. Boolean Operators were used with a combination of the keywords "spine" OR "neck" And "Shoulder". Furthermore, reference lists from papers were also searched to find literature. Results: It is of pivotal importance to conduct comprehensive preoperative clinical investigation to appropriately evaluate and assess the source of the pathology and the leading causes behind it. Certain markers can help guide surgeons towards etiologies, and these include areas of pain and physical exam findings with the arm squeeze test having the highest sensitivity and specificity for diagnosing cervical radiculopathy. As for the shoulder, despite its low sensitivity, the Yergason test had the highest specificity for diagnosing subacromial impingement. Local anesthetic injection can help as well in the diagnostic approach. Moreover, the interplay between these anatomic locations is not solely related to preoperative diagnosis. Studies have shown that previous surgery for cervical spine pathology may negatively affect the outcomes of shoulder procedures like arthroplasties. Conclusion: Shoulder and spine surgeons should be wary and vigilant of accurately diagnosing the etiology of the presenting symptoms to ensure proper management and optimize prognosis.

The role of vitamin D in shoulder health: a comprehensive review of its impact on rotator cuff tears and surgical results.

Vitamin D deficiency is highly prevalent in the general population and is associated with various chronic health conditions. In addition to its role in bone mineralization, Vitamin D has various physiological effects that may impact the pathogenesis of shoulder pathologies. Vitamin D deficiency may also affect outcomes after shoulder surgeries, such as rotator cuff repair and total shoulder arthroplasty. Vitamin D plays a role in tissue healing, bone growth, and maintenance of homeostasis in skeletal muscle cells. Vitamin D also has anti-inflammatory effects that are important to rotator cuff health. Vitamin D deficiency is highly prevalent in patients with rotator cuff tears, suggesting its role as a potential risk factor. Vitamin D deficiency has been associated with decreased preoperative shoulder strength as well as increased re-tear rates, postoperative stiffness, and the need for revision surgery in patients who underwent rotator cuff repair. Studies have also demonstrated a potential association between vitamin D deficiency and increased risk of revision after total shoulder arthroplasty. Further research is necessary to elucidate the direct role of vitamin D in the pathogenesis of rotator cuff tears and its impact on clinical outcomes after rotator cuff surgery and total shoulder arthroplasty.

Unlocking Hope: Anti-VEGFR inhibitors and their potential in glioblastoma treatment.

PURPOSE: This systematic review summarizes evidence of VEGFR gene mutations and VEGF/VEGFR protein expression in glioblastoma multiforme (GBM) patients, alongside the efficacy and safety of anti-VEGFR tyrosine kinase inhibitors (TKIs) for GBM treatment. METHODS: A comprehensive literature review was conducted using PubMed up to August 2023. Boolean operators and MeSH term "glioma," along with specific VEGFR-related keywords, were utilized following thorough examination of existing literature. RESULTS: VEGFR correlates with glioma grade and GBM progression, presenting a viable therapeutic target. Regorafenib and axitinib show promise among studied TKIs. Other multi-targeted TKIs (MTKI) and combination therapies exhibit potential, albeit limited by blood-brain barrier penetration and toxicity. Combining treatments like radiotherapy and enhancing BBB penetration may benefit patients. Further research is warranted in patient quality of life and biomarker-guided selection. CONCLUSION: While certain therapies hold promise for GBM, future research should prioritize personalized medicine and innovative strategies for improved treatment outcomes.

Liquid biopsy as a tool for KRAS/NRAS/BRAF baseline testing in metastatic colorectal cancer.

BACKGROUND: The absence of KRAS and NRAS gene mutations (RAS wild type) in metastatic colorectal cancer (mCRC), is associated with a good response to targeted therapy with anti-EGFR receptor antibodies. The current gold standard for RAS mutational status identification is genetic testing on tissue biopsy samples. OBJECTIVE: This study aimed to assess the relevance of liquid biopsy as a less invasive alternative to tissue biopsy for detecting KRAS/NRAS and BRAF mutations in patients with metastatic colorectal cancer (mCRC). The study also aimed to determine the concordance between liquid biopsy and tissue biopsy. METHODS: This is a phase IV, observational, uncontrolled, non-comparative, non-randomized, open label study. RAS/BRAF status will be tested at baseline using tissue and liquid biopsy using the Idylla/Biocartis PCR-based device. The primary endpoint is the comparison of the RAS status based on liquid biopsy with the RAS status based on tissue biopsy. RESULTS: 100 patients with mCRC were included in the study. 75 % of patients showed concordant results between liquid biopsy and tissue biopsy, while 25 % had discordant results. Liquid biopsy demonstrated a sensitivity of 62 % and a specificity of 93 %. The accuracy of liquid biopsy was 75 %, with a moderate agreement between the two tests. The most frequent mutations in concordant cases were in KRAS (41 %), followed by NRAS (4 %) and BRAF (3 %). Mutations were not detected in 42 % of tissue biopsy samples and 60 % of liquid biopsy samples. The presence of hepatic metastases did not significantly affect the concordance between the biopsy methods. CONCLUSION: Liquid biopsy using the Idylla™ system showed a relatively low sensitivity but high specificity for detecting KRAS/NRAS and BRAF mutations in mCRC patients. Despite some discordant cases, liquid biopsy remains a promising alternative to tissue biopsy due to its non-invasiveness, ability to provide multiple samples, and better representation of tumor heterogeneity.

A rare association of subclavian steal syndrome with bilateral carotid artery stenosis: a case report.

Bilateral carotid artery stenosis in the context of subclavian steal syndrome is an extremely rare finding. We report the case of a 75-year-old woman who presented with a transient ischemic attack. Bilateral internal carotid stenosis associated with left subclavian steal syndrome was diagnosed. Left internal carotid endarterectomy was performed under locoregional anesthesia. Inflation of a blood pressure cuff reversed the neurologic symptoms that appeared after internal carotid clamping. This rarely reported case remains a challenge to diagnose and treat because of its complex mechanisms and multiple risk factors. Our case highlights the importance of the surgical strategy adopted and the need for a good initial assessment.

Osteoporosis in the Setting of Shoulder Arthroplasty: A Narrative Review.

Patients who undergo shoulder surgery are frequently affected by osteoporosis and osteopenia, and the prevalence of this association is expected to increase due to the growing number of elderly individuals undergoing these procedures. It may be advisable to conduct a preoperative DXA scan for orthopedic surgical candidates at high risk, to detect those who could benefit from early intervention and avoid any related adverse events. Some of these complications include periprosthetic fractures, infection, subsequent fragility fractures, and have an all-cause revision arthroplasty at 2 years post-op. Some studies analyzed the beneficence of antiresorptive medications pre-operatively but the latter did not show favorable outcomes. Surgical management may include cementing components of the prosthesis as well as modifying the diameter of the shoulder stem. Nevertheless, more studies are needed to evaluate the efficacy of any intervention, whether medical or surgical, to avoid any shoulder arthroplasty related-complication that may be precipitated by the reduced bone mineral density.

InSpace Balloon for the Management of Massive Irreparable Rotator Cuff Tears: A Systematic Review and Meta-Analysis.

Background: The best course of action for massive irreparable rotator cuff tears (MIRCTs) is not universally agreed upon. Numerous surgical techniques have been discussed. The implantation of a biodegradable spacer into the subacromial area has been documented since 2012 by several authors. The implantation method is touted as being simpler, repeatable, and less invasive than other solutions that are now available. The purpose of this systematic review and meta-analysis, being the first of its kind, was to evaluate the literature to see the efficacy of InSpace balloon (ISB) implantation in the management of MIRCTs. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, and with 2 researchers assessing and analyzing each study separately, an extensive electronic search of the literature was conducted in the PubMed database from 1961 until July 27, 2022. Results: Fourteen studies were included in this systematic review and three in the meta-analysis. Eleven out of fourteen studies favored ISB use for MIRCTs, while only three were against its use. All spacers were arthroscopically implanted in the subacromial space. Three studies were included in the meta-analysis. The differences in the compared outcomes were statistically insignificant. Conclusions: A controversy about the use of ISB remains in patients with MIRCTs. Both good and bad outcomes were reported. However, the majority of patients had good clinical outcomes across several grading scales, radiographic evidence of improved impingement, and self-report that they would redo the procedure in hindsight. To draw more solid conclusions and have statistically significant results in the meta-analysis, more randomized controlled trials and comparative studies comparing this device to other treatments are needed.

Acquired resistance mechanisms to osimertinib: The constant battle.

Lung cancer is the leading cause of cancer-related mortality worldwide. Detectable driver mutations have now changed the course of lung cancer treatment with the emergence of targeted therapy as a novel strategy that widely improved lung cancer prognosis, especially in metastatic patients. Osimertinib (AZD9291) is an irreversible third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) used to treat stage IV EGFR-mutated non-small-cell lung cancer. It was initially designed to target both EGFR-activating mutations and the EGFR T790M mutation as well, which is the most common resistance mechanism to first- and second-generation EGFR-TKIs. Following the FLAURA trial, osimertinib is now widely used in the first-line setting. However, resistance to osimertinib inevitably develops, with numerous mechanisms leading to its resistance, classified into two main categories: EGFR-dependent and EGFR-independent mechanisms. While EGFR-dependent mechanisms consist mainly of the C797S EGFR mutation, EGFR-independent mechanisms include bypass pathways, oncogenic fusions, and phenotypic transformation, among others. This review summarizes the molecular resistance mechanisms to osimertinib, with the aim of identifying novel therapeutic approaches to overcome osimertinib resistance and improve patient outcome.

Tyrosine kinase inhibitors in osteosarcoma: Adapting treatment strategiesa.

Osteosarcoma (OS) is an aggressive primary bone malignancy that metastasizes rapidly. The standard of care has changed little over the previous four decades, and survival rates have plateaued. In this context, tyrosine kinase inhibitors (TKIs) emerge as potential treatments. A literature search was conducted to collect data related to receptor tyrosine kinase genetic alterations and expression in OS specimens. Gene amplification and protein expression of these receptors were linked to prognosis and tumor behavior. Relevant TKIs were evaluated as monotherapies and as parts of combination therapies. Certain TKIs, such as apatinib, regorafenib, and cabozantinib, present a potential therapeutic avenue for OS patients, especially when combined with chemotherapy. Producing long-lasting responses and enhancing quality of life remain key goals in OS treatment. To this effect, optimizing the use of TKIs by identifying biomarkers predictive of response and assessing promising TKIs in larger-scale trials to validate the efficacy and safety outcomes relative to these drugs reported in phase II clinical trials. To this effect, it is necessary to identify biomarkers predictive of response to TKIs in larger-scale trials and to validate the efficacy and safety of these drugs reported in phase II clinical trials.

Molecular and biologic biomarkers of Ewing sarcoma: A systematic review.

With an annual incidence of less than 1%, Ewing sarcoma mainly occurs in children and young adults. It is not a frequent tumor but is the second most common bone malignancy in children. It has a 5-year survival rate of 65-75%; however, it has a poor prognosis when it relapses in patients. A genomic profile of this tumor can potentially help identify poor prognosis patients earlier and guide their treatment. A systematic review of the articles concerning genetic biomarkers in Ewing sarcoma was conducted using the Google Scholar, Cochrane, and PubMed database. There were 71 articles discovered. Numerous diagnostic, prognostic, and predictive biomarkers were found. However, more research is necessary to confirm the role of some of the mentioned biomarkers. .

Epidemiology of bone tumors in Lebanon: a retrospective study from 2000 to 2022 at a tertiary center.

Aim: Bone tumors are rare and have an uneven geographic distribution. Methods: 730 patients diagnosed with bone tumors were included in this retrospective analysis. Results: With a 64% rate of malignancy, the most common tumors were metastasis (40%) mostly in the axial skeleton, Osteosarcoma (9%) mostly in the femur, Osteochondroma (8%) mostly in the femur, giant cell tumors (7%) mostly in the knee, and Ewing's sarcoma (6%) mostly in the axial skeleton. Conclusion: Even though a some of the tumors have a predilection for certain localizations in the human body, they may differ in the middle-eastern population. One must also pay attention to the higher rates of malignancies as compared with other cohorts.

With significant morbidity and mortality, bone tumors incidence is low and varies geographically. In our Lebanese population, Seven-hundred-thirty patients with bone tumors were identified with a 64% rate of malignancy with osteosarcoma being the most common primary bone cancer and metastasis being the overall most prevalent bone malignancy. This higher rate of malignancy compared with other populations should be taken into consideration when evaluating Lebanese or Middle eastern patients.