Effectiveness of physiotherapy in children with functional constipation.

PURPOSE: The objective was to compare the immediate effects of pharmacological versus physiotherapy intervention versus a combination of physiotherapy and pharmacological treatment, as well as the quality of life and the recurrence of symptoms in children with functional constipation after 3 months. METHODS: A total of 69 children with functional constipation between the ages of 5 and 14 years of either gender were assessed and randomly assigned to one of three groups: Group A, B, and C. Visual Analogue Scale, Bristol Stool Form Scale, frequency of defecation, PedsQL GI symptom scale, and PedsQL Generic Core Scale were used as outcome measures. Pharmacology was used to treat Group A, physiotherapy was used to treat Group B, and a combination of both was used to treat Group C. RESULTS: The study revealed statistically significant results on Visual Analogue Scale, Bristol Stool Form Scale, and frequency of defecation in all groups. However, no significant changes were observed on the PedsQL GI symptom scale and the Generic Core scale in Group A, whereas significant changes were observed in Groups B and C. CONCLUSION: In this study, we found that there were significant differences in the short- and long-term effects across all groups. More changes occurred in Group C than in Groups A and B.

Big Decisions on Small Cell Lung Cancer: A Focus on Clinical Care Updates and Patient Perspectives.

Small cell lung cancer (SCLC) is an uncommon, aggressive high-grade neuroendocrine carcinoma, associated with tobacco use. It is a highly chemosensitive disease that initially responds quickly to systemic therapy, although patients with SCLC tend to develop relapse. Although the landscape of SCLC treatment has remained stagnant for many decades, the field has seen notable advances in the past few years, including the use of immunotherapy, the development of further lines of systemic therapy, the refinement of thoracic and intracranial radiotherapy, and-most recently-the promise of more targeted therapies. Patients with SCLC also must face unique psychosocial burdens in their experience with their cancer, distinct from patients with other lung cancer. In this article, we review the latest literature and future directions in the management and investigation of SCLC, as well as the critical decisions that providers and patients must navigate in the current landscape. We also present the perspectives of several patients with SCLC in conjunction with this summary, to spotlight their individual journeys in the context of this challenging disease.

Power-Doppler-based NH002 microbubble sonoporation with chemotherapy relieves hypoxia and enhances the efficacy of chemotherapy and immunotherapy for pancreatic tumors.

Pancreatic ductal adenocarcinoma (PDAC) poses challenges due to late-stage diagnosis and limited treatment response, often attributed to the hypoxic tumor microenvironment (TME). Sonoporation, combining ultrasound and microbubbles, holds promise for enhancing therapy. However, additional preclinical research utilizing commercially available ultrasound equipment for PDAC treatment while delving into the TME's intricacies is necessary. This study investigated the potential of using a clinically available ultrasound system and phase 2-proven microbubbles to relieve tumor hypoxia and enhance the efficacy of chemotherapy and immunotherapy in a murine PDAC model. This approach enables early PDAC detection and blood-flow-sensitive Power-Doppler sonoporation in combination with chemotherapy. It significantly extended treated mice's median survival compared to chemotherapy alone. Mechanistically, this combination therapy enhanced tumor perfusion and substantially reduced tumor hypoxia (77% and 67%, 1- and 3-days post-treatment). Additionally, cluster of differentiation 8 (CD8) T-cell infiltration increased four-fold afterward. The combined treatment demonstrated a strengthening of the anti-programmed death-ligand 1(αPDL1) therapy against PDAC. Our study illustrates the feasibility of using a clinically available ultrasound system with NH-002 microbubbles for early tumor detection, alleviating hypoxic TME, and improving chemotherapy and immunotherapy. It suggests the development of an adjuvant theragnostic protocol incorporating Power-Doppler sonoporation for pancreatic tumor treatment.

Treatment of Acne Scars with Microneedling and Chemical Reconstruction of Scarred Skin Therapy (CROSS) Using Penol/Croton Oil Combination.

BACKGROUND: Microneedling has been shown to release growth factors, which improves the appearance of acne scars by itself and in combination with different therapy modalities. Combining microneedling with Chemical Reconstruction of Scarred Skin (CROSS) therapy using a 60% phenol and 0.2% croton oil combination results in a significant improvement of acne scarring. OBJECTIVE: To assess the safety and efficacy of combination treatments using microneedling in combination with CROSS therapy that contains 60% phenol and 0.2% croton preparation in patients with Fitzpatrick skin types III to V.  Materials and Methods: Patients were treated over a 5-year period for atrophic acne scars using microneedling combined with CROSS. Most of the patients had combination atrophic scarring. High-quality before and after photographs were taken of the patients to assess the improvement in the scars.  Results: Most of the patients (89.5%) had Fitzpatrick skin types IV through V.  Analysis was done on a maximum of 3 microneedling sessions with 1 to 3 CROSS sessions. Photographic evaluation using the Global Aesthetic Improvement Scale showed an 18% grade-1 improvement and 81% grade-2 improvement. The Goodman and Baron Qualitative scar grading system showed a 62% grade-1 improvement and 38% grade-2 improvement. CONCLUSION: Combination treatments work best for atrophic scars. This is the first published report of using microneedling with a 60% phenol/0.2% croton oil combination. It proved to be very effective and safe in treating atrophic acne scars in Fitzpatrick skin types III to V, with minimal side effects and a quick recovery. J Drugs Dermatol. 2024;23(6):418-422.     doi:10.36849/JDD.7657.

Long-term outcomes and prognosis of neuroendocrine neoplasms of the head and neck: a cohort from a single institution.

BACKGROUND: Neuroendocrine neoplasm is a rare cancer of head and neck. This study aimed to evaluate clinical features, treatment outcomes, and prognostic factors of neuroendocrine neoplasm of head and neck treated at a single institution. METHODS: Between Nov 2000 and Nov 2021, ninety-three patients diagnosed with neuroendocrine neoplasms of head and neck treated at our institution were reviewed retrospectively. The initial treatments included chemotherapy (induction, adjuvant, or concurrent) combined with radiotherapy in 40 patients (C + RT group), surgery followed by post-operative RT in 34 (S + RT group), and surgery plus salvage therapy in 19 patients (S + Sa group). RESULTS: The median follow-up time was 64.5 months. 5-year overall survival rate (OS), progression-free survival rate (PFS), loco-regional relapse-free survival free rate (LRRFS) and distant metastasis-free survival rate (DMFS) were 64.5%, 51.6%, 66.6%, and 62.1%, respectively. For stage I-II, the 5-year LRRFS for patients' treatment regimen with or without radiotherapy (C + RT and S + RT groups versus S + Sa group) was 75.0% versus 12.7% (p = 0.015) while for stage III-IV, the 5-year LRRFS was 77.8% versus 50.0% (p = 0.006). The 5-year DMFS values for patients with or without systemic therapy (C + RT group versus S + RT or S + Sa) were 71.2% and 51.5% (p = 0.075). 44 patients (47.3%) experienced treatment failure and distant metastasis was the main failure pattern. CONCLUSIONS: Radiotherapy improved local-regional control and played an important role in the management of HNNENs. The optimal treatment regimen for HNNENs remains the combination of local and systemic treatments.

Enhanced abscopal anti-tumor response via a triple combination of thermal ablation, IL-21, and PD-1 inhibition therapy.

Despite the success of immune checkpoint inhibitors (ICIs) in treating solid tumors, lots of patients remain unresponsive to this therapy. Microwave ablation (MWA) stimulates systemic adaptive immunity against tumor cells by releasing tumor antigens. Additionally, IL-21 has demonstrated importance in stimulating T-cell effector function. The combination of these three therapies-MWA, IL-21, and anti-PD-1 monoclonal antibodies (mAbs)-has yet to be explored in the context of cancer treatment.In this study, we explored the impact of thermal ablation on IL-21R expression in tumor-infiltrating lymphocytes (TILs). Subsequently, we assessed alterations in the tumor microenvironment (TME) and peripheral lymphoid organs. Additionally, we conducted a thorough examination of tumor-infiltrating CD45+ immune cells across various treatment groups using single-cell RNA sequencing (scRNA-seq). Moreover, we determined the potential anti-tumor effects of the triple combination involving MWA, IL-21, and anti-PD-1 mAbs.Our findings revealed that MWA upregulated the expression of IL-21R on various immune cells in the untreated tumors. The combination of MWA with IL-21 exhibited a robust abscopal anti-tumor effect, enhancing the effector function of CD8+ T cells and facilitating dendritic cells' maturation and antigen presentation in the untreated tumor. Notably, the observed abscopal anti-tumor effect resulting from the combination is contingent upon T-cell recirculation, indicating the reliance of systemic adaptive immunity for this treatment regimen. Additionally, the combination of MWA, IL-21, and PD-1 mAbs demonstrated profound abscopal anti-tumor efficacy. Our findings provide support for further clinical investigation into a triple combination therapy involving MWA, IL-21, and ICIs for the treatment of metastatic cancer.

Preclinical evaluation of cyclophosphamide and fludarabine combined with CD19 CAR-T in the treatment of B-cell hematologic malignancies in vivo.

Background: Chimeric antigen receptor T (CAR-T) cell therapy has achieved marked therapeutic success in ameliorating hematological malignancies. However, there is an extant void in the clinical guidelines concerning the most effective chemotherapy regimen prior to chimeric antigen receptor T (CAR-T) cell therapy, as well as the optimal timing for CAR-T cell infusion post-chemotherapy. Materials and Methods: We employed cell-derived tumor xenograft (CDX) murine models to delineate the optimal pre-conditioning chemotherapy regimen and timing for CAR-T cell treatment. Furthermore, transcriptome sequencing was implemented to identify the therapeutic targets and elucidate the underlying mechanisms governing the treatment regimen. Results: Our preclinical in vivo evaluation determined that a combination of cyclophosphamide and fludarabine, followed by the infusion of CD19 CAR-T cells five days subsequent to the chemotherapy, exerts the most efficacious therapeutic effect in B-cell hematological malignancies. Concurrently, RNA-seq data indicated that the therapeutic efficacy predominantly perturbs tumor cell metabolism, primarily through the inhibition of key mitochondrial targets, such as C-Jun Kinase enzyme (C-JUN). Conclusion: In summary, the present study offers critical clinical guidance and serves as an authoritative reference for the deployment of CD19 CAR-T cell therapy in the treatment of B-cell hematological malignancies.

Incorporating Music Therapy With Acupuncture in Managing Cancer Pain at an Acupuncture Practice.

BACKGROUND: Complementary and alternative medicine encompasses various nonpharmacologic interventions for managing pain, such as acupuncture and music therapy. Few studies have combined these two interventions in the management of cancer-related pain. OBJECTIVES: The purpose of this evidence-based project was to compare acupuncture-only therapy versus dual therapy (acupuncture and music therapy) on pain intensity scores in patients with cancer. METHODS: This evidence-based project included 102 participants at a private acupuncture practice. One group had acupuncture only for six weeks, and another had six weeks of acupuncture and music therapy. The Numeric Pain Rating Scale was used to assess pain before and after the interventions. FINDINGS: Findings showed that both groups had clinically and statistically significant improvements in pain intensity scores. Although a significant difference was not noted between the two groups, acupuncture and music therapy were each found to be effective for managing cancer-related pain.

Synergistic antitumor immune response mediated by paclitaxel-conjugated nanohybrid oncolytic adenovirus with dendritic cell therapy.

Dendritic cell (DC)-based vaccines have emerged as a promising strategy in cancer immunotherapy due to low toxicity. However, the therapeutic efficacy of DC as a monotherapy is insufficient due to highly immunosuppressive tumor environment. To address these limitations of DC as immunotherapeutic agent, we have developed a polymeric nanocomplex incorporating (1) oncolytic adenovirus (oAd) co-expressing interleukin (IL)-12 and granulocyte-macrophage colony-stimulating factor (GM-CSF) and (2) arginine-grafted bioreducible polymer with PEGylated paclitaxel (APP) to restore antitumor immune surveillance function in tumor milieu and potentiate immunostimulatory attributes of DC vaccine. Nanohybrid complex (oAd/APP) in combination with DC (oAd/APP+DC) induced superior expression level of antitumor cytokines (IL-12, GM-CSF, and interferon gamma) than either oAd/APP or DC monotherapy in tumor tissues, thus resulting in superior intratumoral infiltration of both endogenous and exogenous DCs. Furthermore, oAd/APP+DC treatment led superior migration of DC to secondary lymphoid organs, such as draining lymph nodes and spleen, in comparison with either monotherapy. Superior migration profile of DCs in oAd/APP+DC treatment group resulted in more prolific activation of tumor-specific T cells in these lymphoid organs and greater intratumoral infiltration of T cells. Additionally, oAd/APP+DC treatment led to lower subset of tumor infiltrating lymphocytes and splenocytes being immunosuppressive regulatory T cells than any other treatment groups. Collectively, oAd/APP+DC led to superior induction of antitumor immune response and amelioration of immunosuppressive tumor microenvironment to elicit potent tumor growth inhibition than either monotherapy.

[Treatment strategies for recurrent rectal cancer]. / Therapiestrategien beim Rektumkarzinomrezidiv.

Multimodal treatment approaches with neoadjuvant radiotherapy and chemotherapy followed by oncological and total mesorectal excision (TME) have significantly reduced the recurrence rate even in locally advanced rectal cancer. Nevertheless, up to 10% of patients develop a local relapse. Surgical R0 resection is the only chance of a cure in the treatment of locally recurrent rectal cancer (LRRC). Due to the altered anatomy and physiology of the true pelvis as a result of the pretreatment and operations as well as the localization and extent of the recurrence, the treatment decision is individualized and remains a challenge for the interdisciplinary team. Even locally advanced tumors with involvement of adjacent structures can be treated in designated centers using multimodal treatment concepts with potentially curative intent.

Effectiveness and safety of the ablative fractional 2940-nm Er: YAG laser for the treatment of androgenetic alopecia.

Laser sources have established their potential effect in inducing hair regrowth. No large cohort study has evaluated the effect of ablative fractional 2940-nm erbium yttrium aluminum garnet (Er: YAG) laser in the treatment of androgenetic alopecia (AGA). To investigate the efficacy and safety of the ablative fractional 2940-nm Er: YAG laser in combination with medication therapy for the treatment of AGA. We performed a retrospective study between first July 2021 to 30th December 2021. All included patients received oral finasteride and topical minoxidil, or combined with six sessions of Er: YAG laser at 2-week intervals. Patients were divided into medication or combined therapy groups. The efficacy of the two therapies was evaluated by the investigator's Global Assessment (IGA) scores and the patient's Likert satisfaction scale at week 12 and week 24. Changes in total, terminal and villous hair count, total and terminal hair diameter, and AGA grade were also recorded. Adverse events were evaluated at each follow-up. A total of 192 male patients with AGA were included, including 67 receiving combination treatment, and 125 receiving medication treatment. At week 24, the combination treatment afforded superior outcomes in the IGA score, patient's global assessment, total and terminal hair counts, and diameters (all P<0.05). No severe adverse events were reported in both groups. The combined therapy of ablative fractional Er: YAG laser and medication was superior in treating male AGA than single medication therapy without serious adverse effects.

Combination of proton- or X-irradiation with anti-PDL1 immunotherapy in two murine oral cancers.

Combining radiation therapy with immunotherapy is a strategy to improve both treatments. The purpose of this study was to compare responses for two syngeneic head and neck cancer (HNC) tumor models in mice following X-ray or proton irradiation with or without immune checkpoint inhibition (ICI). MOC1 (immunogenic) and MOC2 (less immunogenic) tumors were inoculated in the right hind leg of each mouse (C57BL/6J, n = 398). Mice were injected with anti-PDL1 (10 mg/kg, twice weekly for 2 weeks), and tumors were treated with single-dose irradiation (5-30 Gy) with X-rays or protons. MOC2 tumors grew faster and were more radioresistant than MOC1 tumors, and all mice with MOC2 tumors developed metastases. Irradiation reduced the tumor volume in a dose-dependent manner. ICI alone reduced the tumor volume for MOC1 with 20% compared to controls, while no reduction was seen for MOC2. For MOC1, there was a clear treatment synergy when combining irradiation with ICI for radiation doses above 5 Gy and there was a tendency for X-rays being slightly more biologically effective compared to protons. For MOC2, there was a tendency of protons being more effective than X-rays, but both radiation types showed a small synergy when combined with ICI. Although the responses and magnitudes of the therapeutic effect varied, the optimal radiation dose for maximal synergy appeared to be in the order of 10-15 Gy, regardless of tumor model.

Efficacy of neoadjuvant chemotherapy combined with surgery in patients with nonsmall cell lung cancer: A meta-analysis.

INTRODUCTION: This meta-analysis sought to investigate the effect of neoadjuvant chemotherapy (NACT) combined with surgery in patients with nonsmall cell lung cancer (NSCLC). METHODS: With time span from January 2010 to December 2022, PubMed, Web of Science and Embase, China National Knowledge Infrastructure, and WanFang databases were searched for randomized controlled trials on comparison between NACT combined with surgery and surgery alone in patients with NSCLC. Then a meta-analysis was performed in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: A total of 1511 studies were retrieved and 12 were finally included. Meta-analysis results showed that compared with surgery alone, a combination of NACT and surgery was associated with higher treatment response rate (odds ratio, OR = 2.459, 95% confidence interval, CI [1.785, 3.388], P < 0.001), 1-year survival rate (OR = 2.185, 95% CI [1.608, 2.970], P < 0.001), and 3-year survival rate (OR = 2.195, 95% CI [1.568, 3.073], P < 0.001) and lower levels of intraoperative blood loss (standardized mean difference, SMD = -0.932, 95% CI [-1.588, -0.275], P = 0.005) and length of hospital stay (SMD = -0.481, 95% CI [-0.933, -0.028], P = 0.037). CONCLUSION: NACT combined with surgery is superior to surgery alone in the treatment of NSCLC and can promote postoperative recovery. Collectively, such combination is a safe and effective treatment for patients with NSCLC.

Efficacy of ganglion impar block combined with pudendal nerve pulsed radiofrequency for pudendal neuralgia management-a randomized clinical trial.

BACKGROUND: Pudendal neuralgia is a chronic and debilitating condition. Its prevalence ranges from 5 to 26%. Currently, therapeutic approaches to treat pudendal neuralgia include patient education, medication management, psychological and physical therapy, and procedural interventions, such as nerve block, trigger point injections, and surgery. Drug therapy has a limited effect on pain relief. A pudendal nerve block may cause a significant decrease in pain scores for a short time; however, its efficacy significantly decreases over time. In contrast, pudendal nerve pulsed radiofrequency can provide pain relief for 3 months, and ganglion impar block has been widely used for treating chronic perineal pain and chronic coccygodynia. This study aimed to determine the efficacy and safety of monotherapy (pudendal nerve pulsed radiofrequency) and combination therapy (pudendal nerve pulsed radiofrequency plus ganglion impar block) in patients with pudendal neuralgia. METHODS: This randomized, controlled clinical trial will include 84 patients with pudendal neuralgia who failed to respond to drug or physical therapy. Patients will be randomly assigned into one of the two groups: mono or combined treatment groups. The primary outcome will be a change in pain intensity measured using the visual analog scale. The secondary outcomes will include a Self-Rating Anxiety Scale score, Self-Rating Depression Scale score, the use of oral analgesics, the Medical Outcomes Study Health Survey Short Form-36 Item score, and the occurrence of adverse effects. The study results will be analyzed using intention-to-treat and per-protocol analyses. Primary and secondary outcomes will be evaluated between the mono and combined treatment groups. Subgroup analyses will be conducted based on the initial ailment, age, and baseline pain intensity. The safety of the treatment will be assessed by monitoring adverse events, which will be compared between the two groups. DISCUSSION: This study protocol describes a randomized, controlled clinical trial to determine the efficacy and safety of mono and combination therapies in patients with pudendal neuralgia. The study results will provide valuable information on the potential benefits of this combination therapy and contribute to the development of more effective and safer treatments for patients with pudendal neuralgia. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2200061800).

Pediatric and Adolescent Hodgkin Lymphoma: Paving the Way for Standards of Care and Shared Decision Making.

Hodgkin lymphoma (HL) is a treatable cancer with an incidence peak in adolescent and young adult years. Treatment strategies have been developed to balance the intensity of therapy needed to maintain disease-free survival while simultaneously preserving overall survival. Risk-based, response-adapted frontline therapy has long used a combination of chemotherapy and radiotherapy (RT). Successive clinical trials over the past three decades have safely reduced cumulative alkylator, anthracycline, and RT exposures for many patients. The advent of checkpoint inhibitors and the CD30-targeted antibody drug conjugate, brentuximab vedotin, has provided new options for de-escalation of conventional therapies associated with late effects in survivors treated at a young age. The ability to evaluate novel agents has been accelerated in collaborative trials inclusive of children and adolescents within the US National Clinical Trials Network and between the Children's Oncology Group and the EuroNet Pediatric Hodgkin Lymphoma Consortium. With numerous treatment options, patients with HL and their clinicians have an opportunity for shared decision making from diagnosis, through cancer treatment, and into survivorship. Given excellent survival outcomes, decisions about treatment in classic HL should be collaborative and attention to long-term survivorship needs should remain a high priority. Patient-reported outcomes remain an important tool to aid clinicians working with survivors to optimize health status and related quality of life for decades after HL therapy.

The synergistic immunotherapeutic impact of engineered CAR-T cells with PD-1 blockade in lymphomas and solid tumors: a systematic review.

Currently, therapies such as chimeric antigen receptor-T Cell (CAR-T) and immune checkpoint inhibitors like programmed cell death protein-1 (PD-1) blockers are showing promising results for numerous cancer patients. However, significant advancements are required before CAR-T therapies become readily available as off-the-shelf treatments, particularly for solid tumors and lymphomas. In this review, we have systematically analyzed the combination therapy involving engineered CAR-T cells and anti PD-1 agents. This approach aims at overcoming the limitations of current treatments and offers potential advantages such as enhanced tumor inhibition, alleviated T-cell exhaustion, heightened T-cell activation, and minimized toxicity. The integration of CAR-T therapy, which targets tumor-associated antigens, with PD-1 blockade augments T-cell function and mitigates immune suppression within the tumor microenvironment. To assess the impact of combination therapy on various tumors and lymphomas, we categorized them based on six major tumor-associated antigens: mesothelin, disialoganglioside GD-2, CD-19, CD-22, CD-133, and CD-30, which are present in different tumor types. We evaluated the efficacy, complete and partial responses, and progression-free survival in both pre-clinical and clinical models. Additionally, we discussed potential implications, including the feasibility of combination immunotherapies, emphasizing the importance of ongoing research to optimize treatment strategies and improve outcomes for cancer patients. Overall, we believe combining CAR-T therapy with PD-1 blockade holds promise for the next generation of cancer immunotherapy.