Treatment Advances in Lung Cancer with Leptomeningeal Metastasis.

Leptomeningeal metastasis (LM) is a serious and often fatal complication in patients with advanced lung cancer, resulting in significant neurological deficits, decreased quality of life, and a poor prognosis. This article summarizes current research advances in treating lung cancer with meningeal metastases, discusses clinical challenges, and explores treatment strategies. Through an extensive review of relevant clinical trial reports and screening of recent conference abstracts, we collected clinical data on treating patients with lung cancer with meningeal metastases to provide an overview of the current research progress. Exciting progress has been made by focusing on specific mutations within lung cancer, including the use of EGFR tyrosine kinase inhibitors or inhibitors for anaplastic lymphoma kinase gene rearrangement, such as osimertinib, alectinib, and lorlatinib. These targeted therapies have shown impressive results in penetrating the central nervous system (CNS). Regarding whole-brain radiotherapy, there is currently some controversy among investigators regarding its effect on survival. Additionally, immune checkpoint inhibitors (ICIs) have demonstrated reliable clinical benefits due to their ability to retain anticancer activity in CNS metastases. Moreover, combination therapy shows promise in providing further treatment possibilities. Considerable progress has been made in the clinical research of lung cancer with LM. However, the sample size of prospective clinical trials investigating LM for lung cancer is still limited, with most reports being retrospective. Developing more effective management protocols for metastatic LM in lung cancer remains an ongoing challenge for the future.

A New Trend in Cancer Treatment: The Combination of Epigenetics and Immunotherapy.

In recent years, immunotherapy has become a hot spot in the treatment of tumors. As an emerging treatment, it solves many problems in traditional cancer treatment and has now become the main method for cancer treatment. Although immunotherapy is promising, most patients do not respond to treatment or develop resistance. Therefore, in order to achieve a better therapeutic effect, combination therapy has emerged. The combination of immune checkpoint inhibition and epigenetic therapy is one such strategy. In this review, we summarize the current understanding of the key mechanisms of how epigenetic mechanisms affect cancer immune responses and reveal the key role of epigenetic processes in regulating immune cell function and mediating anti-tumor immunity. In addition, we highlight the outlook of combined epigenetic and immune regimens, particularly the combination of immune checkpoint blockade with epigenetic agents, to address the limitations of immunotherapy alone.

The critically ill brain after cardiac arrest.

Cardiac arrest can cause hypoxic-anoxic ischemic brain injury due to signaling cascades that lead to damaged cell membranes and vital cellular organelles, resulting in cell death in the setting of low or no oxygen. Some brain areas are more prone to damage than others, so patients with hypoxic-anoxic ischemic brain injury present with several outcomes, including reduced level of consciousness or alertness, memory deficits, uncoordinated movements, and seizures. Some patients may have mild deficits, while others may have such severe injury that it can progress to brain death. High-quality cardiopulmonary resuscitation is a proven technique to improve outcome after cardiac arrest, although morbidity and mortality remain high. Induced hypothermia, which involves artificially cooling the body immediately after cardiac arrest, may reduce injury to the brain and improve morbidity and mortality. Neuroprognostication after cardiac arrest is challenging and requires a multimodal approach involving clinical neurologic examinations, brain imaging, electrical studies to assess brain activity, and biomarkers to predict outcome.

Commentary: Morphoproteomics and Data Mining of the Medical Literature Define the Pathobiology of COVID-19 Pneumonitis in Humans and Provide Adjuvant Therapeutic Options.

Due to the resurgence of COVID-19, understanding the biology of SARS-CoV-2 is an opportunity to develop adjuvant therapies that could target its pathobiology and lessen the severity of the COVID-19 infection so that our patients could survive. This commentary serves to accomplish this by using published morphoproteomic findings with data mining of the medical literature to define the pathobiology of COVID-19 pneumonitis and provide combinatorial and relatively non-toxic adjuvant therapies that have been successful against this viral infection.

Clinical Outcomes of Thoracolumbar Burst Fracture Treated by Trans-Kambin triangle versus Transpedicular Bone Grafting Combined with Posterior Internal Fixation.

OBJECTIVE: The ideal management of thoracolumbar burst fracture (TLBF) remains controversial. We conducted this study to compare the effectiveness and safety of trans-Kambin triangle versus transpedicular bone grafting combined with posterior internal fixation (PIF) for TLBF. METHODS: Fifty-four patients were retrospectively analyzed and divided into 2 groups: the observation group (PIF combined with bone grafting via the Kambin triangle, n = 28) and the control group (PIF combined with bone grafting via transpedicular, n = 26). The anterior vertebral height ratio, sagittal Cobb angle, visual analog scale score, Oswestry Disability Index, bone healing rate, and neurologic complications were measured. RESULTS: All patients were followed up regularly for a mean period of 17.94 months (12 - 24 months). The anterior vertebral height ratio in the observation group was higher than that in the control group (93.93 ± 2.92 vs. 89.90 ± 5.54%, P = 0.006), and the loss of correction was lower (1.59 ± 1.20 vs. 3.00 ± 1.98%, P = 0.008). The observation group had lower sagittal Cobb angle at final follow-up (8.68 ± 3.75 vs. 11.33 ± 4.77 degrees, P = 0.046) and less correction loss (1.96 ± 1.32 ± 1.15 vs. 3.90 ± 2.39 degrees, P = 0.002). The visual analog scale score and Oswestry Disability Index in the observation group were lower (0.61 ± 0.43 vs. 0.92 ± 0.38, P = 0.016; 15.86 ± 4.11 vs. 19.18 ± 4.04, P = 0.010), while the fracture healing rate showed no significant difference (P > 0.05). No internal fixation failure or neurologic complications occurred in both groups during the follow-up. CONCLUSIONS: Bone grafting via the Kambin triangle combined with PIF is a safe and effective technology for thoracolumbar burst fracture.

Patent ductus arteriosus treatment trends and associated morbidities in neonates.

To evaluate national epidemiologic data on infants treated for patent ductus arteriosus (PDA) in Korea and analyze outcomes associated with different PDA treatments. We retrospectively evaluated data on 12,336 patients diagnosed with PDA (International Classification of Diseases-10 code: Q250) between 2015 and 2018 from the Health Insurance Review and Assessment database. Among them, 1623 patients underwent surgical ligation (code: O1671). We used birth certificate data from Statistics Korea to estimate the prevalence, diagnosis, and treatment of PDA. The prevalence of infants with PDA was 81 infants per 10,000 live births and 45.2% in very low birth weight (VLBW) infants, which increased from 2015 to 2018. PDA ligation was performed in 2571 infants and 22% VLBW infants. Medical treatment was administered to 4202 infants, which decreased significantly, especially in VLBW infants (62% to 53%). The proportion of treatment was as follows: conservative treatment (53.1%), intravenous ibuprofen (24.4%), surgery (20.4%), and oral ibuprofen (10.7%); that among 4854 VLBW infants was as follows: intravenous ibuprofen (46.3%), conservative treatment (33.2%), surgery (22.2%), and oral ibuprofen (14.2%). Surgical treatment had a significantly higher risk (odds ratio 1.36) of mortality than conservative treatment. Surgical and/or medical treatments were associated with a higher risk of morbidity. Recently, increased use of conservative management of PDA has contributed to improved neonatal outcomes in VLBW infants. Select patients may still benefit from surgical ligation following careful consideration.

Analysis of nationwide multimodal complex treatment and drug pump therapy in Parkinson's disease in times of COVID-19 pandemic in Germany.

INTRODUCTION: During the first peak phase of the COVID-19 pandemic, the German Ministry of Health recommended that elective treatments should be postponed to increase hospital capacities. This has also compromised the capacity for application of specialized Parkinson's disease (PD) therapies to an unknown extent. METHODS: We conducted a nationwide cross-sectional study using administrative database of all hospitalized patients with main diagnosis of PD receiving multimodal complex treatment (PD-MCT), initial setup of levodopa/carbidopa intestinal gel (LCIG) or continuous subcutaneous apomorphine infusion (CSAI) in Germany. We compared case numbers and clinical characteristics of the pandemic (March 16th - May 15th, 2020) and post-lockdown (July 16th - September 15th, 2020) period with the pre-pandemic (January 16th - March 15th, 2020) and historical control period (March 16th - May 15th, 2019). RESULTS: We identified a strong decline for PD-MCT(-62.8%) and for the application of drug pump-based therapies (-69.4%) during the first peak phase of the pandemic as compared to the pre-pandemic period while specialized PD treatment procedures increased again in the post-lockdown phase. Advanced disease was a marker for PD-MCT patients during the pandemic period. CONCLUSION: Besides the marked decline in specialized PD treatments during the first peak phase of the COVID-19 pandemic, we found recuperative effects for these procedures in the post-lockdown period without reaching pre-pandemic levels. Strengthening treatment capacities for PD patients, even in the event of a persistent pandemic, is urgently needed in order to maintain the quality of care.

Application of phototherapeutic-based nanoparticles in colorectal cancer.

Colorectal cancer (CRC) is the third most commonly diagnosed malignancy and the second leading cause of cancer death, which accounts for approximately 10% of all new cancer cases worldwide. Surgery is the main method for treatment of early-stage CRC. However, it is not effective for most metastatic tumors, and new treatment and diagnosis strategies need to be developed. Photosensitizers (PSs) play an important role in the treatment of CRC. Phototherapy also has a broad prospect in the treatment of CRC because of its low invasiveness and low toxicity. However, most PSs are associated with limitations including poor solubility, poor selectivity and high toxicity. The application of nanomaterials in PSs has added many advantages, including increased solubility, bioavailability, targeting, stability and low toxicity. In this review, based on phototherapy, we discuss the characteristics and development progress of PSs, the targeting of PSs at organ, cell and molecular levels, and the current methods of optimizing PSs, especially the application of nanoparticles as carriers in CRC. We introduce the photosensitizer (PS) targeting process in photodynamic therapy (PDT), the damage mechanism of PDT, and the application of classic PS in CRC. The action process and damage mechanism of photothermal therapy (PTT) and the types of ablation agents. In addition, we present the imaging examination and the application of PDT / PTT in tumor, including (fluorescence imaging, photoacoustic imaging, nuclear magnetic resonance imaging, nuclear imaging) to provide the basis for the early diagnosis of CRC. Notably, single phototherapy has several limitations in vivo, especially for deep tumors. Here, we discuss the advantages of the combination therapy of PDT and PTT compared with the single therapy. At the same time, this review summarizes the clinical application of PS in CRC. Although a variety of nanomaterials are in the research and development stage, few of them are actually on the market, they will show great advantages in the treatment of CRC in the near future.

Rosacea: New Concepts in Classification and Treatment.

Rosacea is a chronic inflammatory dermatosis mainly affecting the cheeks, nose, chin, and forehead. Rosacea is characterized by recurrent episodes of flushing or transient erythema, persistent erythema, phymatous changes, papules, pustules, and telangiectasia. The eyes may also be involved. Due to rosacea affecting the face, it has a profound negative impact on quality of life, self-esteem, and well-being. In addition to general skin care, there are several approved treatment options available for addressing these features, both topical and systemic. For some features, intense pulse light, laser, and surgery are of value. Recent advances in fundamental scientific research have underscored the roles of the innate and adaptive immune systems as well as neurovascular dysregulation underlying the spectrum of clinical features of rosacea. Endogenous and exogenous stimuli may initiate and aggravate several pathways in patients with rosacea. This review covers the new phenotype-based diagnosis and classification system reflecting pathophysiology, and new and emerging treatment options and approaches. We address new topical and systemic formulations, as well as recent evidence on treatment combinations. In addition, ongoing studies investigating novel therapeutic interventions will be summarized.

Editorial for the Special Issue "Squamous Cell Cancer of the Head and Neck-Time to Arrive in the 21st Century of Oncology".

Squamous cell carcinoma of the head and neck (HNSCC) is the sixth most common cancer worldwide [...].

Pitfalls, challenges, and updates in adjuvant systemic treatment for resected biliary tract cancer.

Introduction: Unfortunately, potentially curative surgical resection is possible in approximately the 25% of biliary tract cancer (BTC) patients at diagnosis, and even following radical surgery, relapse rates remain high. Thus, the role of adjuvant systemic treatment has been widely explored in this setting over the last decades, with the hope of lowering recurrence rates and improving outcomes of BTC patients.Areas covered: In this review, we provide an overview of available evidence regarding adjuvant systemic therapy in resected BTC, critically discussing the pros and cons of recently published clinical trials such as the BILCAP, the BCAT, and the PRODIGE-12/ACCORD-18 phase III studies.Expert opinion: Although the BILCAP trial has established adjuvant capecitabine for 6 months following radical resection as a novel standard of care, the role of adjuvant systemic chemotherapy is the object of debate and controversy in the BTC medical community. Although most of the international guidelines on BTC management have not yet been updated, the recently published ASCO guidelines support the use of capecitabine in this setting. Several phase I to III clinical trials are currently evaluating the role of novel therapeutic approaches in patients with resected BTC, and the results of these studies are highly awaited.

Non-invasive approaches to functional recovery after spinal cord injury: Therapeutic targets and multimodal device interventions.

This paper is an interdisciplinary narrative review of efficacious non-invasive therapies that are increasingly used to restore function in people with chronic spinal cord injuries (SCI). First presented are the secondary injury cascade set in motion by the primary lesion and highlights in therapeutic development for mitigating the acute pathophysiologic process. Then summarized are current pharmacological strategies for modulation of noradrenergic, serotonergic, and dopaminergic neurotransmission to enhance recovery in bench and clinical studies of subacute and chronic SCI. Last examined is how neuromechanical devices (i.e., electrical stimulation, robotic assistance, brain-computer interface, and augmented sensory feedback) could be comprehensively engineered to engage efferent and afferent motosensory pathways to induce neuroplasticity-based neural pattern generation. Emerging evidence shows that computational models of the human neuromusculoskeletal system (i.e., human digital twins) can serve as functionalized anchors to integrate different neuromechanical and pharmacological interventions into a single multimodal prothesis. The system, if appropriately built, may cybernetically optimize treatment outcomes via coordination of heterogeneous biosensory, system output, and control signals. Overall, these rehabilitation protocols involved neuromodulation to evoke beneficial adaptive changes within spared supraspinal, intracord, and peripheral neuromuscular circuits to elicit neurological improvement. Therefore, qualitatively advancing the theoretical understanding of spinal cord neurobiology and neuromechanics is pivotal to designing new ways to reinstate locomotion after SCI. Future research efforts should concentrate on personalizing combination therapies consisting of pharmacological adjuncts, targeted neurobiological and neuromuscular repairs, and brain-computer interfaces, which follow multimodal neuromechanical principles.

Advances in the development of personalized neoantigen-based therapeutic cancer vaccines.

Within the past decade, the field of immunotherapy has revolutionized the treatment of many cancers with the development and regulatory approval of various immune-checkpoint inhibitors and chimeric antigen receptor T cell therapies in diverse indications. Another promising approach to cancer immunotherapy involves the use of personalized vaccines designed to trigger de novo T cell responses against neoantigens, which are highly specific to tumours of individual patients, in order to amplify and broaden the endogenous repertoire of tumour-specific T cells. Results from initial clinical studies of personalized neoantigen-based vaccines, enabled by the availability of rapid and cost-effective sequencing and bioinformatics technologies, have demonstrated robust tumour-specific immunogenicity and preliminary evidence of antitumour activity in patients with melanoma and other cancers. Herein, we provide an overview of the complex process that is necessary to generate a personalized neoantigen vaccine, review the types of vaccine-induced T cells that are found within tumours and outline strategies to enhance the T cell responses. In addition, we discuss the current status of clinical studies testing personalized neoantigen vaccines in patients with cancer and considerations for future clinical investigation of this novel, individualized approach to immunotherapy.

Actinic Keratoses: Reconciling the Biology of Field Cancerization with Treatment Paradigms.

This Perspective briefly reviews the relationship between UV-induced mutations in habitually sun-exposed human skin and subsequent development of actinic keratoses (AKs) and skin cancers. It argues that field therapy rather than AK-selective therapy is the more logical approach to cancer prevention and hypothesizes that treatment early in the process of field cancerization, even prior to the appearance of AKs, may be more effective in preventing cancer as well as more beneficial for and better tolerated by at-risk individuals. Finally, the Perspective encourages use of rapidly advancing DNA analysis techniques to quantify mutational burden in sun-damaged skin and its reduction by various therapies.

History of Endoscopic Ear Surgery.

The introduction of the microscope to ear surgery by Wullstein has been a transformative event in ear surgery. The ability to visualize disease and anatomy has resulted in more effective surgery and better functional outcomes. Many surgical disciplines have adapted the endoscope as the instrument of choice to access and correct internal pathology without disruption of overlying tissue. Multiple discussions and attempts at using the endoscope in ear surgery over the years have culminated in the development of transcanal endoscopic ear surgery. This article discusses the integration of the endoscope into the practice of otologic surgery.

Herpes Simplex Virus Oncolytic Immunovirotherapy: The Blossoming Branch of Multimodal Therapy.

Oncolytic viruses are smart therapeutics against cancer due to their potential to replicate and produce the needed therapeutic dose in the tumor, and to their ability to self-exhaust upon tumor clearance. Oncolytic virotherapy strategies based on the herpes simplex virus are reaching their thirties, and a wide variety of approaches has been envisioned and tested in many different models, and on a range of tumor targets. This huge effort has culminated in the primacy of an oncolytic HSV (oHSV) being the first oncolytic virus to be approved by the FDA and EMA for clinical use, for the treatment of advanced melanoma. The path has just been opened; many more cancer types with poor prognosis await effective and innovative therapies, and oHSVs could provide a promising solution, especially as combination therapies and immunovirotherapies. In this review, we analyze the most recent advances in this field, and try to envision the future ahead of oHSVs.

Advances of aptamer-based clinical applications for the diagnosis and therapy of cancer.

Aptamers are short single-stranded oligonucleotides that have attracted considerable attention due to their favorable biological characteristics. Aptamers can specifically target and bind to proteins or tumor cells, achieving tumor diagnosis and therapy in vitro and in vivo. Following an introduction of methodologies of producing aptamers and the recent advances of aptamers being applied to clinical samples or xenograft tumors, tumor diagnosis using aptamers will be reviewed, including fluorescence imaging, radionuclide-based imaging, MRI, histochemical imaging, and multimodality imaging. Preclinical applications in tumor therapy in vivo will also be discussed, covering different kinds of treatment mechanisms, including aptamer therapeutics, chemotherapy, gene therapy, immunotherapy, and combination therapy. Safety and efficacy of tumor-targeting therapeutics via aptamers, as well as the current challenges and future perspectives about aptamers' clinical applications, will be summarized.

Hybrid dialysis: a promising strategy to reduce hospital access during the SARS-CoV-2 pandemic.

In March 2020, a 74-year-old man affected by end-stage renal disease and on peritoneal dialysis was referred to an emergency room in Modena, Northern Italy, due to fever and respiratory symptoms. After ruling out COVID-19 infection, a diagnosis of chronic obstructive pulmonary disease exacerbation was confirmed and he was thus transferred to the nephrology division. Physical examination and blood tests revealed a positive fluid balance and insufficient correction of the uraemic syndrome, although peritoneal dialysis prescription was maximised. After discussion with the patient and his family, the staff decided to start hybrid dialysis, consisting of once-weekly in-hospital haemodialysis and home peritoneal dialysis for the remaining days. He was discharged at the end of the antibiotic course, after an internal jugular vein central venous catheter placement and the first haemodialysis session. This strategy allowed improvement of depuration parameters and avoidance of frequent access to the hospital, which is crucial in limiting exposure to SARS-CoV-2 in an endemic setting.