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Peri-implant diseases are defined as bacterial plaque-induced inflammatory conditions affecting implant-surrounding tissues and are classified as peri-implant mucositis and peri-implantitis. Peri-implant mucositis is characterized by an inflammatory lesion that resides in the soft tissue compartment, whereas at peri-implantitis sites the lesions also feature progressive loss of implant-supporting bone. Inflammation resolution and disease progression arrestment are the main therapeutic endpoints of the treatment of peri-implant diseases. The present position paper displays the current evidence and clinical recommendations of the European Association for Osseointegration for the treatment of peri-implant diseases. Mechanical biofilm removal along with the reinforcement of patient-administered oral hygiene is considered the standard treatment for managing peri-implant mucositis. It is recommended to assess the outcomes of peri-implant mucositis treatment 2 to 3 months after therapy, and repeated intervention should be considered in the absence of treatment success. Peri-implantitis treatment should follow a stepwise treatment approach, starting with nonsurgical treatment followed by surgical intervention, if that is not sufficient. Surgical peri-implantitis therapies include nonreconstructive, reconstructive, and combined treatment modalities. Implantoplasty may be advocated for the treatment of supracrestal peri-implant defects, whereas reconstructive therapy is indicated at peri-implantitis sites featuring intraosseous defects with a depth ≥ 3 mm. Adjunctive reconstructive measures may be beneficial in enhancing radiographic defect fill and maintaining postoperative soft tissue levels, which may have a great impact in esthetic cases. The adjunctive use of systemic antibiotics during surgical therapy does not seem to improve the clinical outcomes. Regular supportive peri-implant therapy with biofilm removal should be an integral part of the treatment protocol for peri-implant diseases. In the presence of advanced bone loss around implants that do not play a strategic role in masticatory function, implant removal may be considered immediately. [ABSTRACT FROM AUTHOR]

The role of macrophages in regulating the tumor microenvironment has spurned the exponential generation of nanoparticle targeting technologies. With the large amount of literature and the speed at which it is generated it is difficult to remain current with the most up-to-date literature. In this study we performed a topic modeling analysis of 854 abstracts of peer-reviewed literature for the most common usages of nanoparticle targeting of tumor associated macrophages (TAMs) in solid tumors. The data spans 20 years of literature, providing a broad perspective of the nanoparticle strategies. Our topic model found 6 distinct topics: Immune and TAMs, Nanoparticles, Imaging, Gene Delivery and Exosomes, Vaccines, and Multi-modal Therapies. We also found distinct nanoparticle usage, tumor types, and therapeutic trends across these topics. Moreover, we established that the topic model could be used to assign new papers into the existing topics, thereby creating a Living Review. This type of "birds-eye-view" analysis provides a useful assessment tool for exploring new and emerging themes within a large field. [ABSTRACT FROM AUTHOR]

Spasticity management should be provided within the context of a comprehensive person-centered rehabilitation program. Furthermore, active goal setting for specific spasticity interventions is also important, with a well-established "more is better" approach. It is critical to consider adjunctive therapy and multimodal approaches if patients are not attaining their treatment goals. Often used interchangeably, there may be confusion between the terms adjunctive and multimodal therapy. Yet it is imperative to understand the differences between these approaches to achieve treatment goals in spasticity management. Addition of a secondary pharmacologic or non-pharmacologic treatment to optimize the efficacy of the initial modality, such as adding electrical stimulation or casting to BoNT-A, is considered an adjunctive therapy. Adjunctive therapy is time-specific and requires the added therapy be initiated within a specific period to enhance the primary treatment; usually within 2 weeks. Multimodal therapy is an integrated, patient-centric program of pharmacologic and nonpharmacologic strategies utilized in a concurrent/integrated or sequential manner to enhance the overall treatment effect across a variety of spasticityassociated impairments (e.g., neural and non-neural components). Moreover, within a multimodal approach, adjunctive therapy can be used to help enhance the treatment effect of one specific modality. The objectives of this paper are to clarify the differences between adjunctive and multimodal therapies, provide a brief evidence-based review of such approaches, and highlight clinical insights on selecting multimodal and adjunctive therapies in spasticity management. [ABSTRACT FROM AUTHOR]

Introduction: Chronic pain is common after traumatic brain injury (TBI), frequently limits daily activities, and is associated with negative outcomes such as decreased community participation. Despite the negative impact of chronic pain, few people with TBI receive effective treatment. This paper describes a collaborative care (CC) intervention, TBI Care, adapted specifically to treat chronic pain in people living with TBI, emphasizing expert clinician input, cognitive behavioral therapy (CBT) techniques, and other nonpharmacological approaches for decreasing pain interference. Methods: 79participantsengagedintheCCintervention fromtwoacademicmedical rehabilitation clinics with weekly assessments of pain intensity, interference, and medication use. Participant feedback on the intervention was gathered by interview with the care manager (CM) at the last treatment session and/or booster session. Provider feedback was gathered by a confidential survey post intervention. Results: Ninety percent of participants received at least 11 of the target 12 sessions with a care manager (CM), the majority occurring over the phone. Participants endorsed an average of 7 pain locations. All participants received pain education, skills in self-monitoring, goal setting/behavioral activation and relaxation training. Pain interference scores (impact on activity and enjoyment), tracked weekly by the CM, significantly decreased across sessions. 89% of participants received recommendations for CBT skills, 65% received referrals for additional treatments targeting pain interference, and 43% received care coordination. 75% of participants reported 6 or more medications/supplements at both the first and last session, with changes recommended primarily for headache treatment. Feedback from participants and providers was positive. Discussion: TBI Care, a novel patient-centered CC approach, was flexibly delivered, tailored to the needs of those living with TBI and chronic pain, with a high level of participant engagement, and satisfaction among participants and providers. This approach, prioritizing pain self-management strategies and other non-pharmacological approaches, along with optimizing pharmacological treatment, led to significant reductions in self-reported pain interference and intensity during the intervention. Using a CC model in TBI is feasible and successfully improved access to evidence-based treatments for chronic pain as well as outcomes for pain interference and intensity. [ABSTRACT FROM AUTHOR]

The study of language landscape has always been the focus of linguistic research, but there are few studies on the world-class tourism language landscape in minority areas. Guilin has always been one of the hottest world-class tourism destinations, with its unique minority character. From the perspectives of multimodal analysis and tourism language landscape construction, this paper discussed the language landscape characteristics of Longyin Road and East-West Lane scenic spots with different orientations and investigated the local people's attitudes towards multilingual signs. The study found that the majority of signs are monolingual and bilingual, predominantly in Chinese and English. Non-textual elements significantly complemented the linguistic landscape, highlighting the need for accurate and diverse multilingual signage to enhance Guilin's world-class tourism image. [ABSTRACT FROM AUTHOR]

Introduction: Considering the increasing number of conservative surgeries (quadrantectomies) for primary breast carcinoma, especially in the early stages, often followed by adjuvant radiotherapy, the incidence of radiation-associated angiosarcoma (RAS) is expected to rise in the coming decades, and it will represent a clinical and therapeutic challenge, as limited data are available due to the rarity and heterogeneity of the disease. Though the prognosis of these patients is poor, a number of clinical and pathological factors can be evaluated to better understand the course of RAS. The aim of this systematic review is to explore the available clinical-pathological, therapeutic, and prognostic data regarding RAS to evaluate its occurrence, diagnosis, treatment, and outcomes. Method: RAS clinical data were identified by a systematic review conducted in five different databases (Medline, Web of Knowledge, Google Scholar, Scopus, and Cochrane). Only RAS works published in English, with access to the full manuscript text, and with clear results, were considered as eligible. Results: We considered 52 papers comprising 319 RAS cases. The patient age at diagnosis ranged from 37 to 93 years, with most cases occurring from 5 to 10 years after breast irradiation. The most common clinical presentation was an aggressive development of macules, papules, or erythematous-violaceous skin discoloration at the site of previous radiation treatment for primary breast carcinoma. Complete surgical excision appeared to be the first-line treatment of the disease, in some cases followed by adjuvant local and/or systemic therapies. Despite different treatments, local recurrence rates ranged from 40% to 90%, leading to negative outcomes and poor prognosis for patients. Conclusion: Although the literature is limited and the data are heterogeneous and contentious, our review aims to highlight the importance of early diagnosis, multimodal treatment, and long-term follow-up of RAS in order to limit and prevent the aggressiveness of this neoplasm. [ABSTRACT FROM AUTHOR]

Bipolar disorder (BD) can be especially challenging to treat due to the dynamic nature of its presentation; there is a critical need for a multimodal approach to adequately address patients' symptoms and quality of life concerns. However, most mental health professionals have not implemented a multimodal approach due to limited dissemination of evidence-based psychosocial interventions for BD and bias towards psychopharmacology-centered treatment. This is despite clear findings from numerous studies that medication alone fails to fully address most patients' needs and that psychosocial interventions lead to fewer relapses and a higher quality of life. This paper aims to review the evidence in support of psychosocial interventions as a key component of the treatment of BD and to highlight obstacles to the implementation of psychosocial treatment approaches. Additionally, we aim to make a case for an increase in the utilization of psychosocial interventions to improve quality of life and functioning for individuals with BD and their families, and to mitigate societal costs. [ABSTRACT FROM AUTHOR]

Background: Although existing studies have shown that both repetitive transcranial magnetic stimulation (rTMS) and music therapy have advantages in the treatment of non‐fluent aphasia, the efficacy of the combination of these two methods remains to be investigated. Aims: To investigate the clinical efficacy of low‐frequency rTMS combined with music therapy on language function and depression in patients with non‐fluent aphasia after stroke. Methods & Procedures: A single‐blind parallel randomised controlled trial was conducted. Sixty patients (mean duration = 93.78 days) with non‐fluent aphasia after stroke were randomly divided into a traditional therapy group (n = 20), a music therapy group (n = 20) and a combined therapy group (n = 20, 1 Hz). The language function and depression were evaluated before and 3 weeks after treatment with the Chinese version of the Western Aphasia Battery scale, Boston Diagnostic Aphasia Examination scale and Stroke Aphasic Depression Questionnaire Hospital Version scale. Outcomes & Results: The combined therapy group was significantly better in all outcomes than the traditional therapy group and was significantly better in depression than the music therapy group. The music therapy group was significantly better in repetition and depression than the traditional therapy group. Language improvement was positively correlated with depression improvement. For adverse events, only two patients in the combined therapy group showed slight dizziness during rTMS treatment and their symptoms improved after rest. Conclusions & Implications: Our preliminary randomised controlled study indicates that low‐frequency rTMS combined with music therapy is feasible and safe in improving language function and depression in non‐fluent aphasia patients after stroke. WHAT THIS PAPER ADDS: What is already known on this subject: Repetitive transcranial magnetic stimulation (rTMS) and music therapy respectively have advantages in the treatment of non‐fluent aphasia after stroke, but whether the combination of the two methods is more effective is still unknown. What this paper adds to the existing knowledge: This is one of the first randomised control trials to investigate whether the clinical efficacy of low‐frequency rTMS combined music therapy for non‐fluent aphasia is better. The findings show that low‐frequency rTMS combined music therapy is superior to traditional therapy in spontaneous speech, auditory comprehension, repetition, naming, aphasia quotient, functional language level and depression, and superior to music therapy in depression, while music therapy is superior to traditional therapy in repetition and depression. What are the potential or actual clinical implications of this work?: Low‐frequency rTMS combined music therapy may be a better method for treatment of non‐fluent aphasia. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a frequent gastrointestinal malignancy with high rates of morbidity and mortality; 85% of these tumours are proficient mismatch repair (pMMR)‐microsatellite instability‐low (MSI‐L)/microsatellite stable (MSS) CRC known as 'cold' tumours that are resistant to immunosuppressive drugs. Monotherapy with programmed death 1 (PD‐1)/programmed death ligand 1 (PD‐L1) inhibitors is ineffective for treating MSS CRC, making immunotherapy for MSS CRC a bottleneck. Recent studies have found that the multi‐pathway regimens combined with PD‐1/PD‐L1 inhibitors can enhance the efficacy of anti‐PD‐1/PD‐L1 in MSS CRC by increasing the number of CD8+ T cells, upregulating PD‐L1 expression and improving the tumour microenvironment. This paper reviews the research progress of PD‐1/PD‐L1 inhibitors in combination with cytotoxic T‐lymphocyte–associated antigen 4 (CTLA‐4) inhibitors, oncolytic virus, intestinal flora, antiangiogenic agents, chemotherapy, radiotherapy and epigenetic drugs for the treatment of pMMR‐MSI‐L/MSS CRC. [ABSTRACT FROM AUTHOR]

Disrupting the reactive oxygen species (ROS) homeostasis in cancer cells offered a therapeutic modality for anti-tumor treatment. However, the therapeutic efficacy of conventional chemodynamic therapy (CDT) was impaired by the insufficient H2O2 concentration in the tumor microenvironment (TME). Herein, we report the preparation of a multifunctional nanoplatform CaO2@PDA–Cu@MnCO with self-supplied H2O2 production and carbon monoxide (CO) delivery in the TME for efficient multimodal therapy. The nanoplatform consists of a calcium peroxide (CaO2) carrier, with which the surface was covered by Cu2+-doped polydopamine layers, and a covalently loaded manganese carbonyl (MnCO) donor. The nanoplatform specifically responded to the acidic TME, thereby releasing Ca2+ and H2O2 that was further decomposed into hydroxyl radicals (˙OH) via the Cu ion catalyzed Fenton-like reaction. Meanwhile, the released CO under 808 nm light irradiation led to mitochondrial dysfunction and increased the accumulation of intracellular ROS. Furthermore, the Ca2+ overloading could result in calcification of the cancer cells. Consequently, CaO2@PDA–Cu@MnCO showed impressive eradication efficacy for 4T1 cancer cells with a low IC50 value, thus offering a promising therapeutic modality for cancer treatment. [ABSTRACT FROM AUTHOR]

The understanding of schizophrenia has remarkably expanded over the past few decades, moving beyond the dopamine hypothesis to encompass neurotransmitter interplays, structural brain changes and genetic and environmental determinants. This has led to innovations in therapeutic interventions that offer improved outcomes. This paper explores past and current treatments available for schizophrenia, the latest pharmacological advances and the significance of psychotherapeutic approaches. [ABSTRACT FROM AUTHOR]

Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent neurodevelopmental disorders in children and adolescents (CAA) and its treatment plan includes a multimodal approach. Psychoeducation is a potential therapeutic modality in the multimodal treatment of ADHD. Psychoeducation intervention generally consists of single or multiple sessions providing education to the recipient regarding ADHD with the aim to facilitate an informed, self‐responsible management of the disorder and to improve the quality of life of patients and their families. Previous reviews have highlighted the positive effects of parental psychoeducation on ADHD symptoms, behavioral problems and social skills of CAA with ADHD. However, the effects of child only and combined parental and CAA psychoeducation interventions are unclear and under investigated. In the current paper, for the first time, we review, individually, the outcomes of parent only psychoeducation, child only psychoeducation and combined parental and CAA psychoeducation across a range of domains in CAA with ADHD. The findings reveal that including psychoeducation in the treatment of ADHD may improve clinical symptoms, social skills, functioning and family relationships in CAA with ADHD. Practitioner points: Child and combined psychoeducation may improve social skills in attention deficit hyperactivity disorder (ADHD).Child and combined psychoeducation may improve functional impairment in ADHD.Parent psychoeducation may reduce parental stress. [ABSTRACT FROM AUTHOR]

Background: Treatment guidelines belong to the most authoritative sources of evidence-based medicine and are widely implemented by health-care providers. Rectal cancer with an annual incidence of over 730,000 new cases and nearly 340,000 deaths worldwide, remains a significant therapeutic challenge. The total mesorectal excision (TME) leads to a dramatic improvement of local control. The addition of neoadjuvant treatment has been proposed to offer further advancement. However, this addition results in significant functional impairment and a decline in the quality of life. Methods: This review critically assesses whether the recommendation for neoadjuvant treatment in current international guidelines is substantiated. A comprehensive search was conducted in July 2022 in PubMed resulting in 988 papers published in English between 2012 and 2022. After exclusions and proofs 19 documents remained for further analysis. Results: Of the 19 guidelines considered in this review, 11 do not recommend upfront surgery, and 12 do not address the issue of functional impairment following multimodal treatment. The recommendation for neoadjuvant therapy relies on outdated references, lacking differentiated strategies based on current utilisation of MRI staging; numerous guidelines recommend neoadjuvant treatment also to subgroups of patients, who may not need this therapy. Also statements regarding conflicts of interest are often not presented. Conclusions: An immediate and imperative step is warranted to align the recommendations with the latest available evidence, thereby affording rectal cancer patients a commensurate standard of care. A meticulous assessment of the guideline formulation process has the potential to avert heterogeneity in the future. [ABSTRACT FROM AUTHOR]

Simple Summary: Neo-adjuvant systemic (NAS) therapy for melanoma is leading the way in immunotherapy for oncology. There is both a strong biological rationale to support NAS therapy, as well as exciting results in terms of superior efficacy to the current standards of care. Simply giving pembrolizumab 3 doses prior to surgery and 14 after rather than all 17 courses as adjuvant therapy only, demonstrated a 23% improvement in event-free survival (EFS). Combination immunotherapy with ipilimumab and nivolumab seems even more potent with ~60% of patients achieving Major Pathologic Responses (MPR) vs. ~25–30% for single agent anti-PD-1. NAS therapy will allow for a tailored approach to the therapy of melanoma patients, which includes a potential safe de-escalation of the extent of surgery and discontinuation of systemic therapy for MPR patients. And early identification of non-responders who can be directed towards clinical trials with novel therapies. These developments are now splashing over to other solid tumors, but there is still a need to develop a bespoke panel of biomarkers to further improve upon the current treatments. NAS therapy will soon become the novel standard of care approach for macroscopic stage III melanoma. Melanoma treatment is leading the neo-adjuvant systemic (NAS) therapy field. It is hypothesized that having the entire tumor in situ, with all of the heterogeneous tumor antigens, allows the patient's immune system to have a broader response to the tumor in all its shapes and forms. This translates into a higher clinical efficacy. Another benefit of NAS therapy potentially includes identifying patients who have a favorable response, which could offer an opportunity for the de-escalation of the extent of surgery and the need for adjuvant radiotherapy and/or adjuvant systemic therapy, as well as tailoring the follow-up in terms of the frequency of visits and cross-sectional imaging. In this paper, we will review the rationale for NAS therapy in resectable metastatic melanoma and the results obtained so far, both for immunotherapy and for BRAF/MEKi therapy, and discuss the response assessment and interpretation, toxicity and surgical considerations. All the trials that have been reported up to now have been investigator-initiated phase I/II trials with either single-agent anti-PD-1, combination anti-CTLA-4 and anti-PD-1 or BRAF/MEK inhibition. The results have been good but are especially encouraging for immunotherapies, showing high durable recurrence-free survival rates. Combination immunotherapy seems superior, with a higher rate of pathologic responses, particularly in patients with a major pathologic response (MPR = pathologic complete response [pCR] + near-pCR [max 10% viable tumor cells]) of 60% vs. 25–30%. The SWOG S1801 trial has recently shown a 23% improvement in event-free survival (EFS) after 2 years for pembrolizumab when giving 3 doses as NAS therapy and 15 as adjuvant versus 18 as adjuvant only. The community is keen to see the first results (expected in 2024) of the phase 3 NADINA trial (NCT04949113), which randomized patients between surgery + adjuvant anti-PD-1 and two NAS therapy courses of a combination of ipilimumab + nivolumab, followed by surgery and a response-driven adjuvant regimen or follow-up. We are on the eve of neo-adjuvant systemic (NAS) therapy, particularly immunotherapy, becoming the novel standard of care for macroscopic stage III melanoma. [ABSTRACT FROM AUTHOR]

Objective The implementation of early rehabilitation programs based on evidence to improve the movement abilities of preterm infants is of particular importance. The evidence about rehabilitation interventions in improving the motor development of preterm infants is diverse and scattered and there is heterogeneity in the type, dose and time of therapeutic interventions. Therefore, the purpose of this review study is to identify the types of rehabilitation interventions (occupational therapy and physiotherapy) in improving the motor skills of infants hospitalized in the intensive care unit. Materials & Methods This is a scoping review study. Research studies and indexed in scientific databases including were available in PubMed/Web of Science/Scopus or retrieved by Google Scholar search engine were searched and reviewed. Inclusion criteria included the report of studies in English and Persian papers published from 2000 to 2023 that were mainly focused and the main subject of early rehabilitation intervention studies (occupational therapy and physiotherapy) on the development of neuromotor skills of preterm infants in the neonatal intensive care unit. After selecting the keywords and organized search, the found articles were matched with the entry criteria and finally considered studies were selected. Results Among the reviewed studies, 15 studies met the inclusion criteria. Among the available studies, 7 studies related to multi-modal interventions and 2 studies related to multi-sensory intervention .2 studies related to neuro-developmental interventions. 2 studies related to interventions implemented by parents--administered. 2 studies related to interventions supporting play exploration and early developmental intervention. Conclusion Based on the findings of this research and the meetings held with experts in this field, we were able to organize early rehabilitation interventions for motor skills of preterm infants in 4 groups: 1) multimodal and multisensory interventions 2) neurodevelopmental interventions 3) parentsadministered interventions 4) supporting play exploration and early developmental intervention to categorize. In this way, all types of therapeutic interventions in improving motor skills of infants were identified. Most of the studies included interventions that were performed in a short period of time and reported short-term effects on motor improvement. Only the supportive play exploration intervention continued after discharge and bridged the gap of early NICU-to-home interventions and reported improved motor development in the short- and long-term (6, 12 months). [ABSTRACT FROM AUTHOR]

Simple Summary: Undifferentiated embryonal sarcoma of the liver is a rare pediatric tumor with a traditionally poor prognosis. Dual treatment with a combination of surgery and chemotherapy has produced much improved outcomes. The sharing and consolidation of various case series and clinical experiences allow for the prompt design of appropriate treatment advice. Even in the event of unresectable or recurrent diseases, other treatment modalities such as orthotopic liver transplantation and radiotherapy can be offered. This review of treatment recommendations for rare undifferentiated embryonal sarcoma of the liver has important clinical use. Undifferentiated embryonal sarcoma of the liver is a rare mesenchymal tumor with a highly malignant potential. It occurs almost exclusively in the pediatric population and typically has a poor outcome. Although previous studies have reported dismal prognoses, recent advances in combined treatment modalities, e.g., surgery and chemotherapy, have given cause for optimism. Even in those diseases not amenable to complete surgical resection or refractory diseases, other treatment modalities, such as liver transplant, have yielded promising results. This paper provides a review of the current treatment modalities for hepatic undifferentiated embryonal sarcoma in children. [ABSTRACT FROM AUTHOR]

Sonodynamic Therapy (SDT) is a non-invasive means of eaneer treatment using focused ultrasound. The synergistic strategy based on SDT for liver cancer has high research significance and clinical translational value. This paper summarized the therapeutic mechanism and common acoustic sensitivities of SDT, analyzed the reasons why it is difficult to satisfy the current treatment of liver cancer tumors based on single mode acoustic dynamic therapy, and focused on the research progress of acoustic dynamic therapy, chemotherapy, photodynamic therapy, photothermal therapy and other dual synergistic treatment modes, as well as multi-mode synergistic therapy based on acoustic dynamic therapy. The aim is to provide reference and guidance for the future SDT collaborative mode treatment of liver cancer and other types of cancer. At the same time, it points out that SDT collaborative therapy still faces problems in the research process, such as the insignificant effect of single therapy and the few studies on multi-modal combined therapy. Finally, it puts forward the development prospect of developing new acoustic sensitizing agents, exploring the mechanism of combined therapy and realizing real-time diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Metal–organic frameworks (MOFs) are unique coordination polymers that have emerged as important candidates for drug delivery in recent years. Herein, we designed a drug delivery system for multi-modal combination therapy (IR-820/DOX@MIL-101-PDA-PEG-F3, simplified as ID@MIL-PPF3). In this study, pH-sensitive nanocarriers MIL-101(Fe) were prepared and loaded with the effective chemotherapy agent doxorubicin (DOX) and the phototherapeutic reagent new indocyanine green (IR-820) using a physical adsorption method. Dopamine was spontaneously polymerized in alkaline solutions to form a hybrid coating on MIL-101(Fe) (denoted as ID@MIL-101-PDA). The surface of ID@MIL-101-PDA was functionalized by the synthesized polymer NH2-PEG-OCH3/F3 to obtain ID@MIL-PPF3. Characterization results show that ID@MIL-PPF3 has a good drug loading rate (27.7%) and photothermal conversion efficiency (28.89%). In addition, Fe3+ released from MIL-101(Fe) can engage in a Fenton-like reaction to generate hydroxyl radicals (˙OH) to realize chemodynamic therapy (CDT). ID@MIL-PPF3 not only demonstrates the ability to intelligently release drugs, but also realizes chemotherapy combined with PDT/PTT/CDT therapy for tumor cells, which was proved by in vitro evaluation. In conclusion, ID@MIL-PPF3 provides a new idea and method for building a multi-modal combination therapy targeted drug delivery platform. [ABSTRACT FROM AUTHOR]

Introduction: Each year the interdisciplinary AGO (Arbeitsgemeinschaft Gynäkologische Onkologie, German Gynecological Oncology Group) Breast Committee on Diagnosis and Treatment of Breast Cancer provides updated state-of-the-art recommendations for early and metastatic breast cancer. Methods: The updated evidence-based treatment recommendations for early and metastatic breast cancer have been released in March 2024. Results and Conclusion: This paper concisely captures the updated recommendations for early breast cancer chapter by chapter. [ABSTRACT FROM AUTHOR]

This paper offers an insight into the use of Proton Beam Therapy (PBT) in paediatric patients with rhabdomyosarcoma (RMS). This paper provides a comprehensive analysis of the literature, investigating comparative photon-proton dosimetry, outcome, and toxicity. In the complex and multimodal scenario of the treatment of RMS, clear evidence of the therapeutic superiority of PBT compared to other modern photon techniques has not yet been demonstrated; however, PBT can be considered an excellent treatment option, in particular for young children and patients with specific primary sites, such as the head and neck area (and especially the parameningeal regions), genito-urinary, pelvic, and paravertebral regions. The unique depth-dose characteristics of protons can be exploited to achieve significant reductions in normal tissue doses and may allow an escalation of tumour doses and greater sparing of normal tissues, thus potentially improving local control while at the same time reducing toxicity and improving quality of life. However, access of children with RMS (and more in general with solid tumors) to PBT remains a challenge, due to the limited number of available proton therapy installations. [ABSTRACT FROM AUTHOR]

Background: Childhood Sjögren's Disease (cSjD) is an underdiagnosed phenomenon with clinical and pathophysiological nuances in contrast to Sjögren's Disease (SjD) in the adult population. While adults typically experience sicca symptoms, children with cSjD often present with recurrent parotitis, diverse autoantibody profiles, and renal and neurological manifestations. Diagnosis and classification in pediatric rheumatology remain controversial due to the reliance on adult-focused diagnostic criteria and the lack of standardized treatment and understanding of outcomes. The purpose of the paper is to propose a multimodal treatment plan and demonstrate the effectiveness of sialendoscopy in the management of cSjD. Case Presentation: We present the case of a twelve-year-old female diagnosed with cSjD using the 2016 American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) diagnostic criteria for SjD. In addition to medical management, she underwent sialendoscopy with triamcinolone irrigation under sedation and was monitored for progress via salivary gland ultrasonography (SGUS). Over the course of one year, she demonstrated significant improvement in symptoms, with serial SGUS scores gradually decreasing by five points. Conclusions: This paper proposes a multimodal treatment plan involving sialendoscopy and medical management as a non-invasive and potentially more effective approach for cSjD. Standardized monitoring through SGUS scoring allows objective and quantifiable measurement of treatment progress, enabling better assessment of glandular tissue status. Recurrence is possible, and each cSjD patient may present differently. Nevertheless, our year-long observation of a patient with cSjD demonstrates that sialendoscopy, as seen in adults, can promote remission of recurrent parotitis in children as well. [ABSTRACT FROM AUTHOR]

Simple Summary: Non-small cell lung cancers (NSCLCs) can be treated with chemotherapy, radiotherapy, immunotherapy, or a combination before undergoing surgical resection. However, uncertainty remains regarding the overall outcomes of patients undergoing minimally invasive surgical (MIS) resection of the lung, following systemic treatment. As such, we studied the existing data on outcomes of this patient population via a comprehensive dive into the literature and performed a meta-analysis. Our findings indicate that MIS can be safely performed following systemic treatment in patients with NSCLC. Notably, MIS resection offers added benefits including significantly higher lymph node yield compared to open surgery. We also address the various complication rates of both open and MIS surgical approaches, underscoring the importance of surgeon preparedness to convert MIS approaches to open surgeries in precarious circumstances. Overall, this study provides valuable insights into the safety and efficacy of MIS resection post-systemic treatment for patients with NSCLC, offering potential improvements in patient outcomes and guidance to surgical decision making. Background: Minimally invasive surgeries for non-small cell lung cancers (NSCLCs) such as video-assisted thoracoscopic surgeries (VATSs) and robotic-assisted thoracoscopic surgeries (RATSs) have become standard of care for patients needing surgical resection in early stages. The role for neoadjuvant systemic therapy has increased with patients receiving neoadjuvant systemic chemotherapy and immunotherapy. However, there has been some equipoise over the intraoperative and overall outcomes for these patients. Here, we review the current data regarding outcomes of patients undergoing minimally invasive thoracic surgical resection after systemic chemotherapy, immunotherapy, or both. Methods: A systematic literature review of randomized controlled trials and observational studies presenting data on patients with NSCLC that underwent neoadjuvant systemic therapy followed by minimally invasive surgery was performed assessing complications, conversion rates, and lymph node yield. Results: Our search strategy and review of references resulted in 239 publications to screen with 88 full texts assessed and 21 studies included in our final review. VATS had a statistically significant higher lymph node yield in five studies. The reported conversion rates ranged from 0 to 54%. Dense adhesions, bleeding, and difficult anatomy were the most common reported reasons for conversion to open surgeries. The most common complications between both groups were prolonged air leak, arrhythmia, and pneumonia. VATS was found to have significantly fewer complications in three papers. Conclusions: The current literature supports VATS as safe and feasible for patients with NSCLC after neoadjuvant systemic treatment. Surgeons should remain prepared to convert to open surgeries in those patients with dense adhesions and bleeding risk. [ABSTRACT FROM AUTHOR]

Digital exercise therapies (DET) have the potential to bridge existing care gaps for people living with chronic conditions. Acting as either a standalone, embedded within multi-modal lifestyle therapy, or adjunct to pharmacotherapy or surgery, evidence-based DETs can favorably impact the health of a rapidly growing population. Given the nascent nature of digital therapeutics, the regulatory landscape has yet to mature. As such, in the absence of clear guidelines clinical digital product developers are responsible for ensuring the DET adheres to fundamental principles such as patient risk management and clinical effectiveness. The purpose of this narrative review paper is to discuss key considerations for clinical digital product developers who are striving to build novel digital therapeutic (DTx) solutions and thus contribute towards standardization of product development. We herein draw upon DET as an example, highlighting the need for adherence to existing clinical guidelines, human-centered design and an intervention approach that leverages the Chronic Care Model. Specific topics and recommendations related to the development of innovative and scalable products are discussed which ultimately allow for differentiation from a basic wellness tool and integration to clinical workflows. By embodying a code of ethics, clinical digital product developers can adequately address patients' needs and optimize their own future digital health technology assessments including appropriate evidence of safety and efficacy. [ABSTRACT FROM AUTHOR]

Background: There is growing evidence to support the use of the psychedelic drug psilocybin for difficult-to-treat depression. This paper compares the cost-effectiveness of psilocybin-assisted psychotherapy (PAP) with conventional medication, cognitive behavioural therapy (CBT), and the combination of conventional medication and CBT. Methods: A decision model simulated patient events (response, remission, and relapse) following treatment. Data on probabilities, costs and quality-adjusted life years (QALYs) were derived from previous studies or from best estimates. Expected healthcare and societal costs and QALYs over a 6-month time period were calculated. Sensitivity analyses were used to address uncertainty in parameter estimates. Results: The expected healthcare cost of PAP varied from £6132 to £7652 depending on the price of psilocybin. This compares to £3528 for conventional medication alone, £4250 for CBT alone, and £4197 for their combination. QALYs were highest for psilocybin (0.310), followed by CBT alone (0.283), conventional medication alone (0.278), and their combination (0.287). Psilocybin was shown to be cost-effective compared to the other therapies when the cost of therapist support was reduced by 50% and the psilocybin price was reduced from its initial value to £400 to £800 per person. From a societal perspective, psilocybin had improved cost-effectiveness compared to a healthcare perspective. Conclusions: Psilocybin has the potential to be a cost-effective therapy for severe depression. This depends on the level of psychological support that is given to patients receiving psilocybin and the price of the drug itself. Further data on long-term outcomes are required to improve the evidence base. [ABSTRACT FROM AUTHOR]

Deep plantar warts are the most common cutaneous lesions of the plantar aspect of the foot caused by Human papilloma Virus (HPV), mostly occur in children and adolescents. Most of the HPV infections are controlled by the humoral or cellular immune responses. But in few of the population groups these are manifested very frequently compared with other group of population. The virus sheds from the lesions and may infect the other sites of the plantar aspect or affect other parts of the body. Here we present a case of plantar warts which was successfully treated with multiple ayurvedic treatment modalities. This paper describes the case of a thirteen-year-old boy who presented to our hospital's outdoor department with plantar warts since seven days. The patient was treated holistically with ayurvedic treatment modalities including soaking feet in lukewarm triphala decoction, topical application of garlic paste with 777 oil and an ayurvedic oral medication, pancha tikta ghrita guggulu, and the patient was cured completely in 20 days with 100% clearance and even after four years of follow up there was no sign of recurrence. The holistic approach of these ayurvedic treatment modalities have proven as effective and safe in treating the plantar warts. [ABSTRACT FROM AUTHOR]

Background: In August 2018, neratinib – an oral, irreversible pan-HER-tyrosine-kinase inhibitor – was approved by the European Commission for the extended adjuvant treatment of adult patients with early-stage, hormone receptor-positive (HR+), HER2 overexpressed/amplified (HER2+) breast cancer who completed trastuzumab-based adjuvant therapy within the last year. Despite recent improvements in long-term outcome, there is still an unmet need to further reduce the risk of recurrence, especially in patients with poor response to neoadjuvant treatment. Summary: National and international guidelines included recommendations for using neratinib. Based on the health technology assessment for neratinib, the Federal Joint Committee (G-BA) in Germany has granted an added benefit for neratinib compared with the standard "watch and wait" strategies. Inclusion in the Reimbursement Code, however, was rejected by the Austrian social insurance companies in July 2020, and neratinib is now in the "No Box" for individual head physician reimbursement. Key Messages: We analysed the value of extended adjuvant therapy with neratinib in early HER2+/HR+ breast cancer based on current data and made recommendations for the evidence-based and economical use of neratinib in Austria. In particular, prognostic factors associated with an increased risk of recurrence following standard therapy are considered. Extended adjuvant therapy should be offered primarily to nodal-positive patients at surgery. For nodal-negative patients, neratinib therapy may be considered in case of large and/or inflammatory primary tumours (T3–4) without pathological complete response after neoadjuvant therapy. For all other patients, neratinib may be considered depending on additional risk factors on an individual basis that should be evaluated by interdisciplinary tumour conferences. [ABSTRACT FROM AUTHOR]

Background: The relationship between the combination of platelet count and neutrophil‐lymphocyte ratio (COP‐NLR) and prognosis in patients with advanced non‐small cell lung cancer (NSCLC) treated with immune checkpoint inhibitor (ICI) combination therapy with chemotherapy remains unclear. Thus, we investigated prognostic factors, including the COP‐NLR, to identify patients who could benefit from the therapeutic efficacy of ICI combination therapy for advanced NSCLC. Furthermore, we evaluated the relationship between the COP‐NLR score during ICI combination therapy and treatment response. Methods: We conducted a retrospective cohort study of 88 patients with NSCLC who initially received ICI combination therapy. The primary outcome was overall survival (OS). The prognostic factors were extracted using the Cox proportional hazards model. The relationship between COP‐NLR score at 3 weeks after starting ICI combination therapy and a good response (complete response [CR] and partial response [PR]) to treatment was analyzed using the chi‐square test. Results: The median OS was 15.7 months. In the multivariable analysis, Eastern Cooperative Oncology Group Performance Status (ECOG PS) 2, distant metastatic sites ≥2, and baseline COP‐NLR scores of 1, 2 were extracted as significant poor prognostic factors. The proportion of patients with CR and PR in the 3‐week COP‐NLR score of 0 group was significantly higher than that in scores of 1, 2 group. Conclusions: Baseline COP‐NLR, ECOG PS, and number of distant metastatic sites were prognostic factors in patients with NSCLC with ICI combination therapy. A lower 3‐week COP‐NLR was associated with a good response to treatment. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to analyse the clinical outcomes of preoperative adjuvant denosumab therapy (PADT) combined with resection and arthrodesis for recurrent grade 3 giant cell tumor of bone (GCTB) in the distal radius. Methods: A retrospective study was conducted on twenty-three patients (8 males, 15 females) who were treated with the adjuvant denosumab combined with en bloc resection (EBR) and arthrodesis for biopsy confirmed recurrent Campanacci III giant cell tumor of bone in the distal radius between January 2015 and December 2022. All 23 patients were treated with wrist arthrodesis reconstruction using autogenous free iliac crest bone graft (ICBG), bridging plate and screws. The local control, metastasis and overall survival were evaluated during the follow-up period. Functional outcomes were evaluated using the Disabilities of the Arm, Shoulder and Hand (DASH) score, Musculoskeletal Tumor Society Score (MSTS-87 and MSTS-93), and grip strength in the follow-up period. Additionally, all surgical or denosumab-related complications that occurred were recorded in this study. Results: Twenty-three patients were included in this retrospective study and no patients were lost in the follow-up period. The average patient age was 32.5 ± 10.2 years (range, 19–53 years) and the mean follow-up time was 35.5 ± 18.4 months (range, 13–72 months). The average tumor length was 71.7 ± 8.7 mm (range, 50 to 85 mm) and bone reconstruction length was 78.5 ± 8.5 mm (range, 60 to 90 mm). Four patients (17.4%) had secondary local recurrence after reoperation and two patients had (8.7%) multiple recurrences. One patient (4.3%) was deceased in the last follow-up due to multiple metastases. The estimated 5-year recurrence-free survival rate was 81.3% and 5-year metastasis-free survival rate was 95.7%. The mean union time was 8.5 ± 1.9 (6–12) months and the overall survivorship of the allograft was 82.7% (21/23) at an average 35 month follow-up. The average MSTS-87 and MSTS-93 scores were 27.8 ± 1.6 (range, from 23 to 30) and 91.5 ± 5.0 (range, from 76 to 100), and the average DASH score was 8.9 ± 3.2 (range, from 3 to 15), respectively. The average grip strength was 64.6 ± 15.7% (range, from 30 to 95%) of the uninvolved side. Eight patients (34.7%) had at least one complication in the follow-up time. Two autografts (8.7%) were removed due to local recurrence and bone nonunion, and the average autograft survival time was 32.8 ± 18.5 months (range, 12 to 72 months). Conclusions: Preoperative adjuvant denosumab therapy (PADT) combined with en bloc resection and arthrodesis is a promising method for the treatment of recurrent Campanacci III GCTB in distal radius with acceptable short-term local control and functional satisfaction. Level of evidence: level IV Therapeutic. [ABSTRACT FROM AUTHOR]

Simple Summary: Neoadjuvant therapy, used before surgery, is an important part of breast cancer treatment. Not only can it shrink tumors, but it can also provide valuable information on how the cancer responds to treatment, which can help physicians tailor further therapy. For aggressive types of breast cancer, such as HER2-positive and triple-negative breast cancers, targeted therapies and immunotherapy are often added to standard chemotherapy. Achieving a complete response to treatment (i.e., total absence of viable tumor from tissue removed during surgery) is usually a good sign, but it does not always mean better long-term outcomes for every patient. This review examines the evolution of neoadjuvant therapy in high-risk breast cancer and discusses recent clinical trials focused on optimizing treatment. It also highlights the need for new approaches to improve outcomes, especially for patients whose cancer does not fully respond to initial treatments. The use of neoadjuvant systemic therapy (NST) has become increasingly important in the treatment of breast cancer because of its various advantages. These include the ability to downstage tumors without compromising locoregional control and the potential to obtain valuable information about clinical and biological response to therapy with implications for individual prognoses. Surgical response assessment paves the way for response-adapted therapy, and pathological complete response (pCR; defined as ypT0/is ypN0) serves as an additional endpoint for drug development trials. Recommended NST regimens commonly consist of anthracyclines and taxane, with dose-dense anthracyclines and weekly paclitaxel often preferred, whenever feasible. For patients with human epidermal growth factor receptor-2 (HER2)-positive tumors, dual anti-HER2 therapy (trastuzumab and pertuzumab) is indicated together with NST in case of elevated risk of recurrence. For patients with triple-negative breast cancer (TNBC), adding carboplatin to NST correlates with improved pCR and survival rates, as does the addition of immune checkpoint inhibitors. For hormone receptor (HR)-positive/HER2-negative cancers, emerging data on NST including immune checkpoint inhibitors may elevate the significance of NST in high-risk luminal breast cancer. Here, we present a synthesis of the results from neoadjuvant clinical trials that aim at optimizing treatment options for patients with high-risk breast cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Cutaneous melanoma (CM) is an aggressive skin cancer that develops from melanocytic cells. The most important prognostic factor is still the vertical tumour thickness according to Breslow. Liver function is associated with better overall patient outcomes and is currently under increasing investigation in cancer patients. Current findings show that liver function is an important factor in different tumour entities and represents a potential biomarker. Therefore, we aimed to evaluate liver metabolism by using liver scores in CM. High tumour thickness (≥1.66 mm) and aspartate transaminase-to-platelet ratio index (APRI ≥ 0.2241) at the initial diagnosis were associated with a worse prognosis in stage I and II melanoma. Background: Neoadjuvant and adjuvant therapies are currently getting increasingly important in cutaneous melanoma (CM) management. However, there is still a lack of prognostic tools to identify which patients have a poor prognosis. There is increasing evidence that the liver score may be a potential prognostic parameter in different tumour types. The aim was to investigate whether established liver scores can establish the prognosis of CM. Methods: According to established methods, the APRI, the MELD score, the MELD-Na score and the De Ritis ratio were calculated from the laboratory values at the time of the initial diagnosis. Survival was compared with the Kaplan–Meier curve and tested with log-rank tests. Risk factors associated with cutaneous melanoma-specific survival (CMSS) and progression-free survival (PFS) were assessed by using the Cox proportional hazards regression model. To determine the diagnostic accuracy, we performed a time-dependent ROC analysis. Results: A total of 423 patients were included, including 141 patients in AJCC stage (2017) I (33.3%), 82 in stage II (19.4%), 128 in stage III (30.3%) and 72 in stage IV (17%). Median time until melanoma-specific death was 99 months (IQR: 37–126). In addition, 37.6% of patients relapsed with a median time to relapse of 88 months (IQR: 17.5–126). In all stages, tumour thickness and ulceration were independent markers for predicting CMSS and PFS (p < 0.05). The multivariable analysis with all stages showed no significant association with CM outcome for liver scores (p > 0.05). The subgroup analysis revealed that the APRI (≥0.2241) was associated with CMSS and PFS in melanoma stages I and II, independently of tumour thickness, age and ulceration (HR 2.57, 95% CI 1.14–5.75; HR 2.94, 95% CI 1.42–6.09, respectively). Conclusions: The 20-year prognosis of AJCC stage I and II CM was dependent on tumour thickness and the APRI. High tumour thickness and an APRI ≥ 0.2241 at the initial diagnosis were associated with a worse prognosis. Future studies should investigate the independent prognostic value of the APRI in low-stage CM. Furthermore, the APRI score could be a potential biomarker for nomograms. [ABSTRACT FROM AUTHOR]

Simple Summary: The primary treatment for operable pancreatic cancer involves surgery followed by adjuvant therapy, with an increasing use of perioperative or neoadjuvant chemotherapy. We performed a network meta-analysis to assess the comparative efficacy of various treatment approaches for resectable pancreatic cancer. A total of 24 studies were incorporated, comparing 21 treatments with surgery in isolation. Eleven treatments showed superior efficacy compared to surgery alone. Excluding Asian studies, the perioperative regimen of gemcitabine combined with nab-paclitaxel was the most effective regimen. The findings endorse the utilization of perioperative and multi-agent chemotherapy as the favored intervention for operable PC in Western nations. The primary treatment for operable pancreatic cancer (PC) involves surgery followed by adjuvant therapy. Nevertheless, perioperative or neoadjuvant chemotherapy (CT) may be used to mitigate the likelihood of recurrence and mortality. This network meta-analysis (NMA) assesses the comparative efficacy of various treatment approaches for resectable PC. A thorough search was carried out on January 31, 2023, encompassing PubMed/MEDLINE, Cochrane Library, and Embase databases. We incorporated randomized clinical trials (RCTs) that compared surgical interventions with or without (neo)adjuvant or perioperative therapies for operable PC. We conducted a fixed-effects Bayesian NMA. We presented the effect sizes in terms of hazard ratios (HRs) for overall survival (OS) along with 95% credible intervals (95% CrIs). The treatment was deemed statistically superior when the 95% credible interval (CrI) did not encompass a null value (hazard ratio < 1). Treatment rankings were established based on the surface under the cumulative ranking curve (SUCRA). A total of 24 studies were incorporated, comparing 21 treatments with surgery in isolation. Eleven treatments showed superior efficacy compared to surgery alone, with HRs ranging from 0.38 for perioperative treatments to 0.73 for adjuvant 5-fluorouracil. After the exclusion of studies conducted in Asia, it was found that the perioperative regimen of gemcitabine combined with nab-paclitaxel was the most effective regimen (SUCRA, p = 0.99). The findings endorse the utilization of perioperative CT, especially multi-agent CT, as the favored intervention for operable PC in Western nations. [ABSTRACT FROM AUTHOR]

Background: During neoadjuvant therapy (NAT), patients with locally advanced breast cancer (LABC) experience psychological distress (PD) and adopt appropriate coping strategies. Objective: This systematic review aimed to examine the prevalence and changes in PD and coping strategies in patients with LABC during NAT and to evaluate effective interventions to reduce their PD. Design: Quantitative (cross-sectional, longitudinal, and interventional) and qualitative studies reporting PD and coping strategies related to NAT during LABC were included. Data sources and methods: PubMed, Cochrane Library, Scopus, ScienceDirect, Wiley Online Library, and Web of Science databases were consulted to gather relevant literature from the first publications until July 25, 2023. Selection was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results: A total of 41 articles were included, of which four were qualitative. The main results showed that the prevalence of depression before NAT ranged from 0% to 46% and that of anxiety from 5.5% to 54%. After NAT, the prevalence of depression ranged from 40% to 78.5% and anxiety accounted for 27%. Additionally, PD decreased during NAT. The main determinants of PD were perceived social support, living in joint families, being affected by COVID-19 infection, delays in diagnosis, and starting neoadjuvant treatment. For coping strategies, after NAT, "resigned coping" decreased, whereas "social support" increased, and active coping strategies were correlated with better PD. Some interventions found a reduction in PD, such as a mobile health application, fasting-mimicking diet, relaxation training, and guided imaging. Conclusion: These findings highlight the importance of considering PD and coping strategies in patients with LABC from diagnosis to the end of NAT. The results suggest that effective psychological interventions should be implemented. [ABSTRACT FROM AUTHOR]

Background/Objectives: The present study examined the effect of 12-week combined exercise training in normobaric hypoxia on arterial stiffness, inflammatory biomarkers, and red blood cell (RBC) hemorheological function in 24 obese older women (mean age: 67.96 ± 0.96 years). Methods: Subjects were randomly divided into two groups (normoxia (NMX; n = 12) and hypoxia (HPX; n = 12)). Both groups performed aerobic and resistance exercise training programs three times per week for 12 weeks, and the HPX group performed exercise programs in hypoxic environment chambers during the intervention period. Body composition was estimated using bioelectrical impedance analysis equipment. Arterial stiffness was measured using an automatic waveform analyzer. Biomarkers of inflammation and oxygen transport (tumor necrosis factor alpha, interleukin 6 (IL-6), erythropoietin (EPO), and vascular endothelial growth factor (VEGF)), and RBC hemorheological parameters (RBC deformability and aggregation) were analyzed. Results: All variables showed significantly more beneficial changes in the HPX group than in the NMX group during the intervention. The combined exercise training in normobaric hypoxia significantly reduced blood pressure (systolic blood pressure: p < 0.001, diastolic blood pressure: p < 0.001, mean arterial pressure: p < 0.001, pulse pressure: p < 0.05) and brachial–ankle pulse wave velocity (p < 0.001). IL-6 was significantly lower in the HPX group than in the NMX group post-test (p < 0.001). Also, EPO (p < 0.01) and VEGF (p < 0.01) were significantly higher in the HPX group than in the NMX group post-test. Both groups showed significantly improved RBC deformability (RBC EI_3Pa) (p < 0.001) and aggregation (RBC AI_3Pa) (p < 0.001). Conclusions: The present study suggests that combined exercise training in normobaric hypoxia can improve inflammatory biomarkers and RBC hemorheological parameters in obese older women and may help prevent cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Background: This study aims to investigate the efficacy of five analgesic strategies combined with conventional physiotherapy program (CPT) in managing chronic shoulder pain. Methods: Two authors independently screened studies, extracted data using a pre-formatted chart, and assessed bias using the Cochrane Risk of Bias tool. A network meta-analysis was performed by the Stata 17.0 and R 4.3.2 software. Results: A total of 14 studies with 862 subjects were identified. These analgesic strategies included extracorporeal shock wave therapy (ESWT), suprascapular nerve block (SSNB), corticosteroid injection (CSI), hyaluronic acid injection (HAI), and kinesio taping (KT). ESWT plus CPT was the most efficient intervention in alleviating pain intensity and improving physical function. SSNB plus CPT was the optimal intervention in improving shoulder mobility. Compared to CPT alone, CSI + CPT only significantly improved the SPADI total score, but showed no difference in pain intensity or shoulder mobility. HAI + CPT showed no significant difference in improving pain intensity, physical function, or shoulder mobility compared to CPT alone. Adding KT to CPT did not yield additional benefits in improving shoulder mobility. Conclusion: Overall, in managing chronic shoulder pain, ESWT + CPT was the most effective intervention for reducing pain intensity and improving physical function. SSNB + CPT was optimal for enhancing shoulder mobility. Future rigorous clinical trials with larger sample sizes and higher methodological rigor are strongly required to confirm the current results. [ABSTRACT FROM AUTHOR]

Background: The effectiveness and safety of acupuncture therapy to delay lung function decline in chronic obstructive pulmonary disease (COPD) remain unclear. This study aimed to determine whether acupuncture, as an adjunctive therapy to COPD-guided medication, could prevent lung function decline. Methods: This randomised, two-centre study was conducted between February 2022 and July 2023. Men and women aged 40–80 years with COPD were recruited. Participants received active or sham acupuncture three times a week (36 sessions total). The primary outcome was the change in the percentage of forced expiratory volume for 1 s to the predicted value (FEV1%) between the baseline and after the intervention. Results: Overall, 238 participants were screened, and 74 (58 men [78.4%]; mean [standard deviation] age, 69.6 [7.2] years) were randomised into the acupuncture and sham acupuncture groups (37 per group). After the intervention, the change in FEV1% was 1.35 (95% confidence interval [CI]: -0.47 to 3.17) and -2.44 (95% CI: -4.56 to -0.33) in the acupuncture and sham acupuncture groups, respectively. The difference was -3.97 (95% CI: -6.2 to -1.74), and the adjusted difference was -3.46 (95% CI: -5.69 to -1.24, P = 0.003) between the groups. A significantly less decline was found in forced expiratory volume for 1 s in the acupuncture group. All treatment-related adverse events (acupuncture = 11, sham = 2) were mild. Conclusions: Compared with sham acupuncture, acupuncture plus medication may delay lung function decline. However, further studies with a larger sample size and longer-term follow-up are needed to clarify the effects. [ABSTRACT FROM AUTHOR]

Simple Summary: In-transit metastases (ITM) are a challenging aspect of advanced melanoma, traditionally treated with surgery. However, recent advances in systemic therapies, such as immune checkpoint inhibitors and targeted treatments, have significantly improved patient outcomes. These modern therapies are now often preferred over surgery alone. This article reviews the benefits of combining systemic and locoregional treatments, highlighting their potential to enhance survival and quality of life for patients with ITM. By integrating these approaches, we aim to provide a comprehensive strategy for optimizing melanoma treatment outcomes. In-transit metastases (ITM) in melanoma present a significant therapeutic challenge due to their advanced stage and complex clinical nature. From traditional management with surgical resection, ITM treatment has evolved with the advent of systemic therapies such as immune checkpoint inhibitors and targeted therapies, which have markedly improved survival outcomes. This study aims to review and highlight the efficacy of both systemic and locoregional treatment approaches for ITM. Methods include a comprehensive review of clinical studies examining the impact of treatments like immune checkpoint inhibitors, targeted therapies, Isolated Limb Perfusion, and electrochemotherapy. The results indicate that combining systemic therapies with locoregional treatments enhances both local disease control and overall survival rates. The introduction of modern immunotherapies has not diminished the effectiveness of locoregional therapies but rather improved patient outcomes when used in conjunction. The conclusions emphasize that a multidisciplinary approach integrating systemic and locoregional therapies offers a promising strategy for optimizing the management of ITM in melanoma patients. This integrated treatment model not only improves survival rates but also enhances the quality of life for patients, suggesting a shift in standard care practices toward more comprehensive therapeutic regimens. [ABSTRACT FROM AUTHOR]

Simple Summary: Melanoma is the deadliest of all skin cancers. Therapy paradigms in cutaneous melanoma have changed significantly over the past 20 years, following both changes in the initial staging work-up of melanoma as well as in the available therapies. Regional recurrences after initial surgery are normally treated with nodal basin resection. However, some regional recurrences may present as bulky masses that can pose significant challenges in the treatment and control of the disease. It is well established that radiation therapy (RT) plays a role in locoregional control of malignancies in general. This review will attempt to discuss evidence for radiation therapy's role in reducing regional recurrence in the adjuvant setting in melanoma, identify adjuvant systemic therapy options, discuss systemic therapy–radiation therapy combinations, and identify paradigms and emerging evidence for the use of radiation therapy after neoadjuvant systemic therapy strategies are employed. In the landscape of Stage III locoregionally advanced cutaneous melanoma treatment, the post-immunotherapy era has sparked a number of questions on the management of the nodal basin. However, much of the available literature is not focused on radiation therapy as an adjuvant therapy. This literature review aims to illuminate the evidence surrounding radiation therapy's potential to mitigate regional recurrences in the adjuvant setting for melanoma. Additionally, it seeks to identify adjunct systemic therapy options and explore the synergy between systemic therapy and radiation. Despite strides in surgical techniques and systemic therapies, controlling regional Stage III melanoma remains a formidable clinical hurdle. While historical data strongly suggest the efficacy of adjuvant radiation therapy in reducing regional recurrence risk, its evaluation predates the advent of MAPK pathway inhibitors and robust immunotherapy options. Notably, clinical trials have yet to definitively demonstrate a survival advantage with adjuvant radiation therapy. Additional research should focus on refining the definition of high risk for regional recurrence through gene expression profiling or tumor immune profiling scores and elucidate the optimal role of adjuvant radiation therapy in patients treated with neoadjuvant systemic therapy. [ABSTRACT FROM AUTHOR]

This study investigates a novel multimodal treatment for chronic tinnitus, a condition that significantly affects quality of life, by combining personalized sound therapy with both low- and high-frequency electromagnetic wave stimulation. Conducted at Tor Vergata University Hospital in Rome, the research involved 55 patients and employed a portable medical device for therapy delivery. Treatment effectiveness was measured through the Tinnitus Functional Index (TFI), Tinnitus Handicap Inventory (THI), Visual Analogue Scale (VAS), Hyperacusis Questionnaire (HQ), and Short Form-36 Health Survey (SF-36), encompassing initial sound therapy and subsequent multimodal treatment phases. Remarkably, 73% of participants experienced notable improvements in TFI scores, with 39% reporting a significant enhancement of 13 points or more. This improvement was mirrored in secondary outcomes like THI, VAS, and HQ scores, along with certain SF-36 domains, indicating enhanced life quality and reduced tinnitus distress. The study underscored high compliance and no adverse effects, suggesting the combined therapy's promising potential in chronic tinnitus management. The findings advocate for further research to discern the distinct contributions of each treatment modality, positing that this innovative approach could ameliorate tinnitus symptoms and improve patient well-being, confirming its safety and efficacy. [ABSTRACT FROM AUTHOR]

Pancreatic cancer comprises different subtypes, where most cases include ductal adenocarcinoma (PDAC). It is one of the deadliest tumor types, with a poor prognosis. In the majority of patients, the disease has already spread by the time of diagnosis, making full recovery unlikely and increasing mortality risk. Despite developments in its detection and management, including chemotherapy, radiotherapy, and targeted therapies as well as advances in immunotherapy, only in about 13% of PDAC patients does the overall survival exceed 5 years. This may be attributed, at least in part, to the highly desmoplastic tumor microenvironment (TME) that acts as a barrier limiting perfusion, drug delivery, and immune cell infiltration and contributes to the establishment of immunologically 'cold' conditions. Therefore, there is an urgent need to unravel the complexity of the TME that promotes PDAC progression and decipher the mechanisms of pancreatic tumors' resistance to immunotherapy. In this review, we provide an overview of the major cellular and non-cellular components of PDAC TME, as well as their biological interplays. We also discuss the current state of PDAC therapeutic treatments and focus on ongoing and future immunotherapy efforts and multimodal treatments aiming at remodeling the TME to improve therapeutic efficacy. [ABSTRACT FROM AUTHOR]

Objectives: Small vessel cerebrovascular disease (SVCVD) accounts for 35% to 67% of vascular dementias, and may be overlooked by healthcare providers due to its insidious onset. SVCVD involves chronic cerebral ischemia and hypoperfusion, endothelial dysfunction, blood-brain barrier disruption, and interstitial fluid reflux. The purpose of this study was to investigate the clinical efficacy of repetitive transcranial magnetic stimulation (rTMS) combined with donepezil hydrochloride compared to donepezil alone in the treatment of mild-to-moderate cognitive impairment in patients with SVCVD. Material and methods: A cohort of 115 individuals with mild-to-moderate cognitive impairment due to SVCVD was purposefully selected and randomized into two groups: a test group and a control group. The test group received a combination of repetitive transcranial magnetic stimulation (rTMS) and oral donepezil hydrochloride (10 mg/day), while the control group received oral donepezil alone (10 mg/day). The Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores were evaluated in both groups prior to and following the interventions. Results: Following 6 weeks of treatment, both groups demonstrated enhancement in cognitive function. However, a statistically significant difference was observed between the test group and the control group (p <.05 on both the MMSE and the MOCA), favoring the test group. Conclusions: Compared to donepezil alone, the combination of repetitive transcranial magnetic stimulation (rTMS) and donepezil has a significantly greater effect on enhancing cognitive function among individuals experiencing mild-to-moderate cognitive impairment resulting from SVCVD. [ABSTRACT FROM AUTHOR]

Background: Breast cancer presents diverse molecular subtypes affecting treatment strategies. Human epidermal growth factor receptor 2 (HER2)-low, hormone receptor-positive (HR+) breast cancer poses a challenge due to limited targeted therapies. Current neoadjuvant treatment primarily utilizes chemotherapy, with conflicting results regarding efficacy in patients with HER2-low breast cancer. Trastuzumab deruxtecan (T-DXd) shows promise in HER2-low metastatic disease, and preliminary evidence suggests synergy with endocrine therapy. Objective: This editorial explores the hypothesis that neoadjuvant T-DXd with or without endocrine therapy offers efficacy in the clinical management of HR+/HER2-low breast cancer. Methods: We propose a phase II study with two treatment arms: T-DXd + letrozole and T-DXd alone. The primary endpoint is the radiological complete response rate. Secondary endpoints include pathological complete response rate, safety, event-free survival, and overall survival. Exploratory analyses will compare the arms to identify potential for optimizing treatment efficacy and minimizing side effects. Conclusions: This study design allows for initial assessment of T-DXd with or without endocrine therapy in the treatment of HER2-low breast cancer. The findings may pave the way for personalized treatment strategies and inform future research, potentially leading to a chemotherapy-sparing approach. [ABSTRACT FROM AUTHOR]

Simple Summary: The indications for neoadjuvant chemotherapy (NAT) have expanded in recent years both for locally advanced and early-stage breast cancer, with different pathological complete response (pCR) rates among different molecular subtypes. This retrospective two-center study aims to evaluate the diagnostic performance of Contrast-Enhanced Mammography (CEM) in assessing the response to NAT in breast cancer patients. The CEM sensitivity and specificity were 66.2% and 75.2%, with the highest specificity (80.9%) in HR+/HER2− and the highest sensitivity (70%) in triple-negative breast cancer. CEM is a valid tool to assess the pCR with different performances among the molecular subtypes and may be reliable in the decisional process of de-escalating surgical management. Neoadjuvant chemotherapy (NAT) plays a crucial role in breast cancer (BC) treatment, both in advanced BC and in early-stage BC, with different rates of pathological complete response (pCR) among the different BC molecular subtypes. Imaging monitoring is mandatory to evaluate the NAT efficacy. This study evaluates the diagnostic performance of Contrast-Enhanced Mammography (CEM) in BC patients undergoing NAT. This retrospective two-center study included 174 patients. The breast lesions were classified based on the molecular subtypes in hormone receptor (HR+)/HER2−, HER2+, and triple-negative breast cancer (TNBC). The histopathological analysis performed following surgery was used as a reference standard for the pCR. Sensitivity, specificity, PPV, and NPV were measured overall and for the different subtypes. We enrolled 174 patients, 79/174 (46%) HR+/HER2−, 59/174 (33.9%) HER2+, and 35/174 (20.1%) TNBC; the pCR was found in 64/174 (36.8%), of which 57.1% were TNBCs. In the total population, the CEM sensitivity and specificity were 66.2% and 75.2%, with a PPV of 61.4% and an NPV of 78.8%. The highest specificity (80.9%) and NPV (91.7%) were found in HR+/HER2−, while the highest sensitivity (70%) and PPV appeared (73.7%) in TNBC. The results indicate that CEM is a valid tool to assess the pCR, with different performances among the subtypes of BC. [ABSTRACT FROM AUTHOR]

Background: Globally, the demographic shift towards an aging population leads to significant challenges in healthcare systems, specifically due to an increasing incidence of multimorbidity resulting in polypharmacy among the elderly. Simultaneously, sleep disorders are a common complaint for elderly people. A treatment with pharmacological therapies often leads to side effects causing a high potential for dependency. Within this context, there is a high need to explore non-pharmacological therapeutic approaches. The purpose of this study is to evaluate the effectiveness of acupuncture and music therapy, both individually and combined as a multimodal therapy, in the treatment of sleep disorders in individuals aged 70 years and older. Methods: We conduct a confirmatory randomized controlled trial using a two-factorial study design. A total of n = 100 elderly people receive evidence-based standard care information for age-related sleep disorders. Beyond that, patients are randomly assigned into four groups of n = 25 each to receive acupuncture, receptive music therapy with a monochord, multimodal therapy with both acupuncture and music therapy, or no further therapy. The study's primary outcome measurement is the improvement in sleep quality as assessed by the Pittsburgh Sleep Quality Index (PSQI) (global score), at the end of intervention. Additionally, depression scores (Geriatric Depression Scale), health-related quality of life (Short-Form-Health Survey-12), neurovegetative activity measured via heart rate variability, and safety data are collected as secondary outcomes. Using a mixed-methods approach, a qualitative process evaluation will be conducted to complement the quantitative data. Discussion: The study is ongoing and the last patient in is expected to be enrolled in April 2024. The results can provide valuable insights into the effectiveness of non-pharmacological interventions for sleep disorders among the elderly, contributing to a more personalized and holistic approach in geriatric healthcare. Trial registration: German Clinical Trials Register (DRKS00031886). [ABSTRACT FROM AUTHOR]

A seminal report, released in 2001 by the Institute of Medicine, spurred research on the design, implementation, and evaluation of multilevel interventions targeting obesity and related behaviors. By addressing social and environmental factors that support positive health behavior change, interventions that include multiple levels of influence (e.g., individual, social, structural) aim to bolster effectiveness and, ultimately, public health impact. With more than 20 years of multilevel obesity intervention research to draw from, this review was informed by published reviews (n = 51) and identified intervention trials (n = 103), inclusive of all ages and countries, to elucidate key learnings about the state of the science. This review provides a critical appraisal of the scientific literature related to multilevel obesity interventions and includes a description of their effectiveness on adiposity outcomes and prominent characteristics (e.g., population, setting, levels). Key objectives for future research are recommended to advance innovations to improve population health and reduce obesity. [ABSTRACT FROM AUTHOR]

Wilms tumor (WT) is the most common kidney tumor in pediatric patients. Intravascular extension of WT above the level of the renal veins is a rare manifestation that complicates surgical management. Patients with intravascular extension are frequently asymptomatic at diagnosis, and tumor thrombus extension is usually diagnosed by imaging. Neoadjuvant chemotherapy is indicated for thrombus extension above the level of the hepatic veins and often leads to thrombus regression, obviating the need for cardiopulmonary bypass in cases of cardiac thrombus at diagnosis. In cases of tumor extension to the retrohepatic cava, neoadjuvant therapy is not strictly indicated, but it may facilitate the regression of tumor thrombi, making resection safer. Hepatic vascular isolation and cardiopulmonary bypass increase the risk of bleeding and other complications when utilized for tumor thrombectomy. Fortunately, WT patients with vena caval with or with intracardiac extension have similar overall and event-free survival when compared to patients with WT without intravascular extension when thrombectomy is successfully performed. Still, patients with metastatic disease at presentation or unfavorable histology suffer relatively poor outcomes. Dedicated pediatric surgical oncology and pediatric cardiothoracic surgery teams, in conjunction with multimodal therapy directed by a multidisciplinary team, are preferred for optimized outcomes in this patient population. [ABSTRACT FROM AUTHOR]

Bladder cancer (BC) is the tenth most commonly diagnosed malignancy worldwide. In approximately 25% of cases, it presents as a muscle-invasive disease, requiring a radical treatment. Traditionally, the mainstay of treatment has been radical cystectomy (RC), but in the last decade, bladder-sparing treatments have been gaining growing interest. In particular, trimodal therapy (TMT) seems to yield survival results comparable to RC with less morbidity and better quality of life (QoL) outcomes. In this scenario, we aimed at shedding light on the role of the histological subtypes (HS) of BC and their prognostic significance in muscle-invasive BC (MIBC), treated either surgically or with TMT. We performed a narrative review to provide an overview of the current literature on this topic. When compared with patients diagnosed with conventional urothelial carcinoma (UC) of the same disease stage, survival did not appear to be significantly worse across the reports. But when sub-analyzed for separate subtype, some appeared to be independently associated with adverse survival outcomes such as the micropapillary, plasmacytoid, small-cell, and sarcomatoid subtypes, whereas others did not. Moreover, the optimal management remains to be defined, also depending on the therapeutic susceptibility of each histology. From this perspective, multi-disciplinary assessment alongside the routine inclusion of such entities in randomized clinical trials appears to be essential. [ABSTRACT FROM AUTHOR]

Introduction. Patients with hormone receptor‐positive (HR+), HER2‐negative (HER2−) breast cancers have the lowest response to neoadjuvant therapy of all subtypes. The role of neoadjuvant endocrine therapy (NET) in clinically node‐positive (cN+), HR+, HER2− patients is evaluated in this meta‐analysis. Methods. This study was performed between January 2010 and August 2022. We evaluated the node pathologic complete response (pCR) and axillary lymph node dissection (ALND) rates after neoadjuvant endocrine therapy (NET). Results. 18,037 HR+, HER2−, cN+ stage II and stage III breast cancer patients within eleven studies received neoadjuvant treatments. 3,707 (20.6%) patients received NET and 14,330 (79.4%) received NAC. The average age of the NET patients was higher than that of the neoadjuvant chemotherapy (NAC) patients (64.1 versus 47.6 years old, p < 0.001). 45.0% and 26.9% of the NET and the NAC groups underwent a lumpectomy. The pooled estimates of node pCR in NET and NAC groups were 8.9% and 14.9%, and the pooled proportion of ALND was 39.1% and 58.5%, respectively. Conclusion. The rate of node pCR was lower among cN+ patients who received NET compared to the NAC group. The rate of ALND among cN+ NET patients was lower than the NAC group, revealing more patients with residual nodal disease do not get ALND in the NET group. Further prospective studies are required to compare survival outcomes as a more reliable surrogate. [ABSTRACT FROM AUTHOR]

Background and Objectives: Hospitals streamline treatment pathways to reduce the length of time older adults admitted for planned procedures spend in hospital. However patient perspectives have been poorly evaluated. This systematic review aimed to understand the experiences of older patients, carers, families and staff of multi‐component interventions intended to improve recovery following elective treatment. Research Design and Methods: Bibliographic databases searched in June 2021 included MEDLINE ALL, HMIC, CENTRAL, CINAHL, AMED and ProQuest Dissertations and Theses. We conducted citation searching and examined reference lists of reviews. Two reviewers independently undertook screening and data extraction, resolving disagreements through discussion. We used an adapted Wallace checklist for quality appraisal and meta‐ethnography to synthesise data. Clinician, carer and patient views were incorporated throughout the review. Results: Thirty‐five papers were included in the synthesis. Thirteen studies were conducted in the UK, with patient views the most frequently represented. We identified six overarching constructs: 'Home as preferred environment for recovery', 'Feeling safe', 'Individualisation of structured programme', 'Taking responsibility', 'Essential care at home' and 'Outcomes'. Discussion and Implications: Findings explore the support patients, families and carers need throughout hospital admission, and may inform commissioning of services to ensure patients and carers receive appropriate follow‐up support after hospital discharge. The findings may help hospital and community‐based health and social care staff provide person‐centred care based upon assessments of emotional and physical wellbeing of patients and family/carers. Research is needed to establish a core‐set of patient‐reported outcome measures which capture aspects of recovery which are meaningful to patients. [ABSTRACT FROM AUTHOR]

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Background: The purpose of this paper is to provide a preliminary evaluation of treatment outcomes, retention and client satisfaction following a 12-week combined cognitive behavioural therapy (CBT) and motivational enhancement therapy (MET) group treatment for cannabis use disorder (CUD) delivered in an outpatient setting. Implementation of the program is also described. Methods: A retrospective observational cohort study was conducted using data collected from medical records and self-report assessments. Participants were treatment-seeking cannabis users at the Centre for Addiction and Mental Health, Toronto. Cannabis use, cannabis-related problems, craving, withdrawal symptoms, self-efficacy for remaining abstinent, depression and anxiety were assessed pre- and post-treatment. Treatment retention was calculated by inspecting clinic attendance records, and client satisfaction was evaluated using an anonymous feedback survey. Potential predictors of treatment outcomes and retention were investigated in exploratory analyses. Results: Cannabis use was lower and days of abstinence higher post-treatment (vs pre-treatment). Post-treatment improvements in cannabis-related problems, craving, withdrawal symptoms, self-efficacy and mood were also observed. Completion of group treatment (⩾75% of sessions attended) was 57% and moderate levels of treatment satisfaction were reported. Conclusions: This study provides preliminary evidence that a 12-week combined CBT and MET treatment for cannabis use disorder delivered in a novel group setting improves cannabis use outcomes. Potential predictors of reduced cannabis use and retention were identified. Future controlled studies are warranted, and strategies for increasing retention should be explored. [ABSTRACT FROM AUTHOR]