Modality Therapy Research Articles

Circulating tumour DNA dynamics predict recurrence in stage III melanoma patients receiving neoadjuvant immunotherapy

BackgroundNeoadjuvant therapy improves recurrence-free survival (RFS) in resectable stage III cutaneous melanoma. However, accurately predicting individual recurrence risk remains a significant challenge. We investigated circulating tumour DNA (ctDNA) as a biomarker for recurrence in measurable stage IIIB/C melanoma patients undergoing neoadjuvant immunotherapy.MethodsPlasma samples were collected pre-neoadjuvant treatment, pre-surgery and/or six weeks post-surgery from 40 patients enrolled in the OpACIN-neo and PRADO clinical trials. Patients received two cycles of ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) before surgery. Cell free DNA (cfDNA) underwent unbiased pre-amplification followed by tumour-informed mutation detection using droplet digital polymerase chain reaction (ddPCR) with the Bio-Rad QX600 PCR system.ResultsPre-treatment ctDNA was detectable in 19/40 (48%) patients. Among these, 17/19 (89%) zero-converted within six weeks of surgery and none recurred. Positive ctDNA post-surgery (N = 4), irrespective of pre-treatment ctDNA status, was 100% predictive of recurrence (sensitivity 44%, specificity 100%). Furthermore, ctDNA cleared prior to surgery in 7/9 (78%) patients who did not recur, warranting further investigation into ctDNA-guided surgical management.ConclusionPost-surgery ctDNA positivity and zero-conversion are highly predictive of recurrence, offering a window for personalised modification of adjuvant therapy.

Does Electroencephalography Seizure Duration Account for an Adequate Treatment of Magnetic Seizure Therapy for Schizophrenia?

A seizure lasting >15 s has been considered to indicate treatment for magnetic seizure therapy (MST), a modification of electroconvulsive therapy (ECT), without much validation. This study aimed to investigate whether this seizure duration was suitable for the treatment of schizophrenia. Altogether, 34 and 33 in-patients with schizophrenia received 10 sessions of MST and ECT, respectively. Clinical symptoms were assessed using the Positive and Negative Symptom Scale at baseline and at the 4-week follow-up. Electroencephalogram (EEG) was monitored during each MST or ECT treatment using bifrontal electrodes. The proportion of participants who achieved the 15-second threshold was only 28.6% in the MST group, with a significant difference between responders and nonresponders. For patients receiving MST, the average EEG seizure duration correlated with the percentage of Positive and Negative Symptom Scale reduction (t(32) = 2.51, P = 0.017, uncorrected; t(32) = 2.00, P = 0.055, corrected with clinical characteristics). The average EEG seizure duration predicted the clinical response at a trend level (Z = 1.76, P = 0.078) with an optimal cutoff of 11.3 seconds. All patients in the ECT group achieved the 15-second threshold. However, their average EEG seizure duration was uncorrelated with clinical improvement. The duration of EEG seizures may be associated with the antipsychotic effects of MST. This association may have been influenced by various clinical and technical factors. More research is needed to define the specific criteria for adequate MST in schizophrenia in order to achieve personalized dosing.

Effectiveness of Use of Transcutaneous Electrical Nerve Stimulation (Tens) Modality To Reduce Pain In The Lower Back: Literature Review

Low back pain (LBP) is a common global health problem that causes disability, increases medical costs, and leads to labor loss. Eighty percent of the population has experienced low back pain at some point in their lives. Chronic low back pain is often associated with comorbidities, significant healthcare costs, and increased use of health services. This study aims to evaluate the effectiveness of Transcutaneous Electrical Nerve Stimulation (TENS) in reducing pain in LBP patients. This study uses a literature review method with strict inclusion and exclusion criteria. The study involved 142 samples, predominantly athletes over 40 years old. The TENS intervention was applied with a frequency of 5 times per week, intensity of 100 Hz, and a duration of 15 minutes for 6 weeks. Pain measurements were conducted using the Visual Analog Scale (VAS) and the Roland Morris Disability Questionnaire (RMQ). The results showed that the intervention group using TENS experienced a significant reduction in pain compared to the control group, with a p-value of <0.001. TENS has proven to be an effective non-invasive therapy method for reducing chronic low back pain. In conclusion, TENS is an effective therapy modality for reducing chronic low back pain and can be used as a non-pharmacological alternative in the management of LBP. Further research is needed to explore the application of TENS in various other clinical conditions.

COVID-19 Disease in Children With ALL Receiving Maintenance Therapy: Do Not Discount the Risk.

Unlike most childhood cancers, therapy for ALL includes a prolonged maintenance phase during which children typically resume regular activities. Physicians need data regarding the persistent impact of COVID-19 in this population to help guide families after the pandemic. The Pediatric Oncology COVID-19 Case Report (POCC) collects deidentified data (sociodemographics, clinical data [cancer, COVID-19 course]) on children, adolescents, and young adults with cancer and COVID-19 from 104 US pediatric oncology institutions. The analysis presented here compares children (≤21 years) with ALL in maintenance (ALL-MTN) with all other children with cancer and COVID-19. Multivariable analyses adjust for age, race/ethnicity, insurance, absolute neutrophil count at the time of infection, vaccination, and comorbidities. Compared with other children reported to POCC (n = 1,190), those in ALL-MTN (n = 481) were less often hospitalized (23% v 29%, P = .01) or admitted to the intensive care unit (ICU: 3% v 5%, P = .01); these findings persisted in multivariable analysis (hospitalization: odds ratio [OR], 0.7 [95% CI, 0.6 to 0.9]; ICU: OR, 0.5 [95% CI, 0.2 to 0.8]). However, cancer-directed therapy was changed more often for children in ALL-MTN (50% v 33%, P ≤ .01; OR, 2.0 [95% CI, 1.6 to 2.5[). Vaccination was an independent prognostic factor in our multivariable model, decreasing odds of hospitalization (OR, 0.7 [95% CI, 0.5 to 0.9]). Children in ALL-MTN required fewer hospitalizations and ICU admissions but more therapy modifications than other children with cancer. Vaccination against COVID-19 reduced the odds of hospitalization.

Targeted 8-arm PEG Nanosystems for Localization of Choroidal Neovascularization Macular Degeneration Model.

8-arm PEG (polyethylene-glycol) is a highly promising nanoplatform due to its small size (<10 nm), ease-of-conjugation (many functionalized variants are readily available with "click-like" properties), biocompatibility, and optical inactivity. This study evaluates 8-arm PEG uptake into cells (in vitro) and localization and clearance in vasculature (in vivo) for targeting of choroidal neovascularization in mice, an animal model of macular degeneration. 8-arm PEG nanoparticles were labeled with fluorescein isothiocyanate (FITC) and functionalized in the absence or presence of pentameric Ar-Gly-Asp (RGD; 4 RGD motifs and a PGC linker), one of the most common peptide motifs used for active targeting. In vitro studies show that RGD-conjugated 8-arm PEG nanoparticles exhibit enhanced cellular uptake relative to non-RGD-conjugated control NPs at 34% ± 9%. Laser-induced choroidal neovascularization (CNV) was performed in a mouse model to measure 8-arm PEG localization and clearance to model macular degeneration lesions in vivo. It was determined that both RGD-conjugated and non-RGD-conjugated (nRGD) 8-arm PEG particles localized to CNV lesions, with a half-life around 24 h. In vivo experiments showed that RGD-conjugated nanoparticles exhibited enhanced localization by 15-20% relative to without RGD controls. Exhibiting a high rate of localization and fast clearance relative to larger nanoparticles, targeted 8-arm PEG nanoparticles with a conjugated RGD-peptide could be a promising modality for macular degeneration diagnosis and therapy.

Advancements in targeting tumor suppressor genes (p53 and BRCA 1/2) in breast cancer therapy.

Globally, among numerous cancer subtypes, breast cancer (BC) is one of the mostprevalent forms of cancer affecting the female population. A female's family history significantly increases her risk of developing breast cancer. BC is caused by aberrant breast cells that proliferate and develop into tumors. It is estimated that 5-10% of breastcarcinomas are inherited and involve genetic mutations that ensure the survival and prognosis of breast cancer cells. The most common genetic variations are responsible for hereditary breast cancer but are not limited to p53, BRCA1, and BRCA2. BRCA1 and BRCA2 are involved in genomic recombination, cell cycle monitoring, programmed cell death, and transcriptional regulation. When BRCA1 and 2 genetic variations are present in breast carcinoma, p53 irregularities become more prevalent. Both BRCA1/2 and p53 genes are involved in cell cycle monitoring. The present article discusses the current status of breast cancer research, spotlighting the tumor suppressor genes (BRCA1/2 and p53) along with structural activity relationship studies, FDA-approved drugs, and several therapy modalities for treating BC. Breast cancer drugs, accessible today in the market, have different side effects includinganemia, pneumonitis, nausea, lethargy, and vomiting. Thus, the development of novel p53 and BRCA1/2 inhibitors with minimal possible side effects is crucial. We have covered compounds that have been examined subsequently (2020 onwards) in this overview which may be utilized as lead compounds. Further, we have covered mechanistic pathways to showcase the critical druggable targets and clinical and post-clinical drugs targeting them for their utility in BC.

Triple Negative Evaluation of FFPE (Formalin Fixed Embedded Tissue) Breast Cancer Tissues in A Tertiary Health Institution of Bayelsa State, Nigeria

Breast cancer is a common disease worldwide, with over two million cases reported in 2018. Various therapy modalities use biological characteristics that influence treatment and outcomes to provide individualized care. Some biomarker advancements, such as hormone receptors, vascular endothelial growth factors, and HER2/neu receptors, have significantly contributed to the biological characterization of breast cancer. Triple-negative breast cancer is defined as malignancies that do not express hormone responsiveness or HER-2. Approximately 12% of women with breast cancer will have triple-negative illness, which is more common among non-Hispanic black women regardless of age, but is detected at a younger age than other subtypes. Women with triple-negative illness are more likely to be diagnosed at a later stage (stage III or IV). The pathogenesis of breast cancer is complex and poorly understood, however many risk factors are known. This cross-sectional study spanned from 2010 to 2022. In this study, the prevalence of triple-negative breast cancer in archived breast cancer cases at Federal Medical Centre Yenagoa, Bayelsa State, was analyzed using the Haematoxylin and Eosin Staining Technique on breast cancer samples collected over the study period. This study, done at Bayelsa State's Federal Medical Centre Yenagoa, analyzed 178 breast specimens. Ninety-six percent (96%) of the patients were IDC, and 5% were TNBC. The average age at presentation was 48.21 years, with 59.1% of patients being under 50 years. 40% of the patients exhibited HER-2/neu positive, and 65% had estrogen receptor (ER) positivity. The study was conducted in a single medical institution, and specific types of lesions were not included. Other potential limitations include comparing findings with various techniques and diagnostic protocols.

Shared decision-making in selecting modality of renal replacement therapy confers better patient prognosis after the initiation of dialysis.

The effect of shared decision-making (SDM) regarding the choice of renal replacement therapy (RRT) for chronic kidney disease (CKD) patients on their mortality after the induction of dialysis therapy has not been adequately investigated. Patients who initiated dialysis at our hospital were divided into two groups according to whether they participated in SDM in the outpatient clinic, and survival analysis was performed. We also examined the effect of SDM in the outpatient clinic on mortality. Of the 554 patients, 123 (22.2%) were in the SDM group. The survival rate was significantly higher in the SDM group (p = 0.001, log-rank test). Multivariate analysis excluding ADL, which competed with SDM, showed that SDM was significantly associated with mortality (HR 0.593, 95% CI: 0.353-0.997, p = 0.049). SDM regarding RRT selection in the outpatient clinic may be associated with a better patient prognosis after dialysis induction.

External breast prostheses after mastectomy: production and selection of a low-cost functional model to be performed in developing countries.

Breast cancer is one of the most common types of cancer affecting women. Despite advancements in early diagnosis, neoadjuvant therapy, and various treatment modalities, mastectomy remains a common procedure for many women. Although some women opt for reconstructive surgery (BR), many do not have the indication, desire, or opportunity to undergo this procedure. An easily manufactured, washable, lightweight, and inexpensive external breast prosthesis (EBP) model was developed specifically for the study. Participants were presented with five EBP models-one commercially available, three manufactured options, and one created for the study-and were asked to choose a prosthesis. We also evaluated the factors associated with non-adherence to EBP among women who had undergone mastectomy without BR. The chi-square test was used to assess adherence or non-adherence to EBP, while logistic regression was used to identify factors associated with non-adherence. We introduced a low-cost, lightweight, washable EBP model. When participants were asked to choose between two prostheses, the silicone prosthesis was the first choice for 33.9% of the participants, while the prosthesis created for the study emerged as the second choice for 70.5%. Out of the 72 women assessed, 45.8% (33) opted not to use any of the EBP models. Our analysis revealed that age and BMI were significantly associated with non-use of EBP. Multiple barriers contribute to non-adherence to EBP, underscoring the need for interventions aimed at improving patient knowledge and adherence. This study introduces a lightweight, easily reproducible, and low-cost EBP model.

Enzyme-Dynamic Extracellular Vesicles for Metalloimmunotherapy of Malignant Pleural Effusions.

Malignant pleural effusions (MPEs) are hard to treat, and their onset usually signals terminal cancer. Immunotherapies hold promise but must overcome the immunosuppressive MPE microenvironment. Herein, we treat MPEs via synergistically combining two emerging cancer therapy modalities: enzyme-dynamic therapy (EDT) and metalloimmunotherapy. To do so, a nanoplatform termed "A-R-SOME" was developed which comprises MPE-targeted M1 type extracellular vesicles (EVs) loaded with (1) a manganese-based superoxide dismutase (SOD) enzyme, (2) stimulator of interferon genes (STING) agonist diABZI-2, and (3) signal transducer and an activator of transcription 3 (STAT3) small interfering RNA. Endogenous reactive oxygen species within tumors induced immunogenic cell death by EDT, along with STING activation by both Mn and diABZI-2, and suppression of the STAT3 pathway. Systemically administered A-R-SOME alleviated the MPE immunosuppressive microenvironment, triggered antitumor systemic immunity, and long-term immune memory, leading to the complete eradication of MPE and pleural tumors with 100% survival rate in an aggressive murine model. A-R-SOME-induced immune effects were also observed in human patient-derived MPE, pointing toward the translation potential of A-R-SOME as an experimental malignancy treatment.

Dynamic Responses of Human Skin and Fascia to an Innovative Stimulation Device-Shear Wave Stimulation.

Exposure to mechanical stimuli such as pressure and stretching prompts the skin to undergo physiological adaptations to accommodate and distribute applied forces, a process known as mechanotransduction. Mechanotherapy, which leverages mechanotransduction, shows significant promise across various medical disciplines. Traditional methods, such as massage and compression therapy, effectively promote skin healing by utilizing this mechanism, although they require direct skin contact. This study introduces a novel contactless modality, Shear Wave Stimulation (SWS), and evaluates its efficacy compared to traditional massage in eliciting responses from human skin and fascia. Fifteen healthy volunteers received SWS, while another fifteen volunteers received massage. Tests of skin mechanical properties revealed significant enhancements in skin shear modulus for both methods, showing an increase of approximately 20%. Additionally, deformation analysis of ultrasound images showed distinct responses of the skin and fascia to the two stimuli. SWS induced extension in the dermis (∼18%), hypodermis (∼16%), and fascia (∼22%) along the X and Y axes. In contrast, massage compressed the skin layers, reducing the dermis by around 15% and the hypodermis by about 8%, while simultaneously stretching the superficial fascia by approximately 8%. The observed extension across the entire skin with SWS highlights its potential as a groundbreaking contactless approach for promoting skin healing. Furthermore, the differing responses in blood flow reaffirm the distinct stimulation modes of SWS and massage. These findings establish a foundation for future innovative skin therapy modalities.

TRANSCUTANEOUS LASER IRRADIATION OF BLOOD IN SIMULTANEOUS MODE (S-ILIB) FOR FATIGUE RECOVERY

The modified transcutaneous laser irradiation on blood (ILIB), a systemic modality of photobiomodulation therapy (PBMT), consists of a laser application on the radial artery or other artery in the body, to improve systemic functions and physiological dynamics of the body. The available therapeutic strategies for the management of fatigue due to daily life stress are mainly focused on lifestyle changes associated with nutrition and exercise. Thus, the present study aims to report a series of cases in which transcutaneous modified ILIB therapy in simultaneous mode (S-ILIB), was used to treat fatigue symptoms. Four healthy patients, without any type of significant comorbidity, reported fatigue related to stress. They were treated by the new PBMT protocol with the modified ILIB technique. The intensity or perception of fatigue was rated using a visual analogue scale (VAS). The "simultaneous technique" used in the present study consisted of laser irradiation in four sites of the body: 1- the radial artery region of the right arm; 2- the radial artery region of the left arm; 3- the right dorsal pedis artery; and 4- the left dorsal pedis artery. For PBMT, two laser device were used at 660 nm, on contact mode, with 100 mW of power. The patients reported a clear recovery in the energy sensation after the S-ILIB session. The PBMT protocol seems to be a promising therapy for managing energy recovery in fatigue-stress-related daily routines; however, complementary studies are required to establish the safest and most efficient protocol

Potentially Inappropriate Medications Involved in Drug-Drug Interactions in a Polish Population over 80 Years Old: An Observational, Cross-Sectional Study.

The clinical context of drug interactions detected by automated analysis systems is particularly important in older patients with multimorbidities. We aimed to provide unique, up-to-date data on the prevalence of potentially inappropriate medications (PIMs) and drug-drug interactions (DDIs) in the Polish geriatric population over 80 years old and determine the frequency and the most common PIMs involved in DDIs. We analyzed all non-prescription and prescription drugs in a representative national group of 178 home-dwelling adults over 80 years old with excessive polypharmacy (≥10 drugs). The FORTA List was used to assess PIMs, and the Lexicomp® Drug Interactions database was used for DDIs. DDIs were detected in 66.9% of the study group, whereas PIMs were detected in 94.4%. Verification of clinical indications for the use of substances involved in DDIs resulted in a reduction in the total number of DDIs by more than 1.5 times, as well as in a nearly 3-fold decrease in the number of interactions requiring therapy modification and drug combinations that should be strictly avoided. The most common PIMs involved in DDIs were painkillers, and drugs used in psychiatry and neurology. Special attention should be paid to DDIs with PIMs since they could increase their inappropriate character. The use of automated interaction analysis systems, while maintaining appropriate clinical criticism, can increase both chances for a good therapeutic effect and the safety of the elderly during treatment processes.

A preliminary investigation into the impact of soft tissue augmentation-based periodontal phenotype modification therapy for patients exhibiting class III decompensation

BackgroundPatients with skeletal angle Class III malocclusion usually have inadequate hard and soft tissue volume at the mandibular anterior teeth. The labial proclination at the teeth may lead to gingival recession. The purpose of this study was to explore whether periodontal phenotype modification therapy with soft tissue augmentation (PhMT-s) can prevent gingival recession in these patients.MethodsFour patients with skeletal Class III malocclusion and a thin periodontal phenotype underwent surgical-orthodontic treatment. Prior to tooth movement, they underwent a minimally invasive vestibular incision with subperiosteal tunnel access combined with autogenous connective tissue grafts for periodontal phenotype modification with soft tissue augmentation (PhMT-s). The labial gingival thickness of the anterior mandibular teeth was measured at three distinct levels: at the cementoenamel junction (GT0), 3 mm apical to the CEJ (GT3), and 6 mm apical to the CEJ (GT6). These measurements were taken at baseline, three months following PhMT-s, and after tooth decompensation. Additionally, a biopsy sample was obtained from the PhMT-s site of one patient. All sections were subsequently stained using hematoxylin and eosin, Masson trichrome, Sirius Red, and immunohistochemistry.ResultsThe thickness of the labial gingiva was increased about 0.42 to 2.00 mm after PhMT-s. At the end of pre-orthognathic surgical orthodontic treatment, the thickness of the labial gingiva was increased about − 0.14 to 1.32 mm compared to the baseline and no gingival recession occurred after the pre-orthognathic surgical orthodontic treatment. The histologic results demonstrated that the grafts obtained from the PhMT-s site exhibited increased deposition of collagen fibers. Moreover, the proportion of type III collagen increased and the grafts displayed significantly reduced positive expression of CD31 and OCN.ConclusionsPhMT-s increased the thickness of the soft tissue, stabilizing the gingival margin for teeth exhibiting a thin periodontal phenotype and undergoing labial movement. This is attributed to the increased deposition of collagen fibers.

Implementation of Cognitive Behavioral Therapy for psychosis via telehealth: An expert consultation and clinical service model.

Individuals living with psychosis are often underserved in the United States, partly due to the dearth of providers trained in evidence-based practices for this population. One such practice is Cognitive Behavioral Therapy for psychosis, which the Substance Abuse and Mental Health Services Administration has identified as a standard of care for this population. The explosion of telehealth, in large part due to the COVID-19 pandemic, has led to increased opportunities for virtual psychotherapy. Telehealth offers a number of benefits, such as the ability to address service inequities, including lack of access to a local provider well-trained in the modality of therapy needed. The current article describes the National Psychosis Telehealth Program within the National Expert Consultation and Specialized Services (formerly VA National Telemental Health Center) program, U.S. Department of Veterans Affairs. The goal of this telehealth program is to utilize an expert consultation model and offer a remote individual, time-limited Cognitive Behavioral Therapy for psychosis protocol to Veterans across the nation in order to decrease access disparities to this relatively scarce service. We share our initiation activities and lessons learned as we developed this program in hopes of encouraging others to consider similar efforts at their sites. We also include a typical, complex case that serves to illustrate the challenges and benefits of this approach. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Perioperative Immunotherapy for Resectable Non-Small Cell Lung Cancer: Current Evidence and New Standard of Care

Immunotherapy has drastically changed the treatment of lung cancer not only in systemic disease but also in the perioperative setting in locally advanced non-small cell lung cancer. In particular, the neoadjuvant and perioperative therapy regimes of the CheckMate 816 and KEYNOTE-671 studies as well as the adjuvant therapy according to the IMPower010 and the PEARLS/KEYNOTE-091 protocols have already been approved by the European Medicines Agency (EMA) for the treatment of selected cases. Other therapy protocols and combination therapies with varying drug classes and therapy modalities are currently being examined for their effectiveness and tolerance. The new treatment landscape creates new opportunities but also challenges for the treating disciplines. This article will focus on the current evidence for perioperative immunotherapy for resectable lung cancer and the resulting therapy standards, especially with regard to patient selection for both neoadjuvant and adjuvant immunotherapy, as well as current research efforts.

Ginsenoside RB1 Influences Macrophage–DPSC Interactions in Inflammatory Conditions

Unresolved inflammation and tissue destruction are supposed to underlie the failure of dental pulp repair. As crucial regulators of the injury response, dental pulp stem cells (DPSCs) play a key role in pulp tissue repair and regeneration. M2 macrophages have been demonstrated to induce osteogenic/odontogenic differentiation of DPSCs. Ginsenoside Rb1 (GRb1) is the major component of ginseng and manifested an anti-inflammatory role by promoting M1 macrophage polarised into M2 macrophage in inflammatory disease. However, whether GRb1 facilitates odontogenic differentiation of DPSCs via promoting M2 macrophage polarisation under inflammatory conditions has yet to be established. Human monocyte leukemic cells (THP-1) differentiated macrophages were induced into M1 subsets and then treated with GRb1. After that, the conditioned medium was added to DPSCs. The cell co-cultured system was then subjected to odontogenic differentiation in osteogenic media. Effects of GRb1 on human dental pulp stem cells' (hDPSCs') osteogenic/odontogenic differentiation under inflammatory conditions were assessed by alkaline phosphatase (ALP) staining, Alizarin Red S (ARS) staining, and quantitative polymerase chain reaction testing. Results demonstrated that GRb1 could facilitate the polarisation of macrophages from the M1 subtype to the M2 subtype. Conditioned medium from GRb1 + M1 macrophages, in comparison with M1 macrophages, may markedly increase the gene expression of ALP, DSPP, and DMP1. Moreover, ALP and ARS staining uncovered that the osteogenic/odontogenic differentiation ability of hDPSCs was strengthened in the M1 + GRb1 co-culture group. GRb1 plays a crucial role in the inflammatory response and reparative dentine formation after dental pulp injury. Findings show that GRb1 modulates the interaction between macrophages and DPSCs during inflammation. The current study discusses modifications of deep caries therapy.

Kidney failure amongst Irish Travellers.

The occurrence of Kidney Failure with Replacement Therapy (KFRT) amongst Irish Travellers has not been well described. This study aims to determine the burden of KFRT amongst the Irish Traveller population and identify determinants of health amongst this cohort which may differ from the general population in Ireland. This retrospective cohort study included self-identifying Irish Travellers with KFRT registered in the National Kidney Disease Clinical Patient Management System between 1995 and 2022. KFRT was defined as Chronic Kidney Disease stage 5 (CKD G5) treated by dialysis or CKD G1-G5 after transplantation. The primary outcome measure was the prevalence of KFRT in Irish Travellers. Secondary exploratory outcomes included age at diagnosis, family history, biopsy diagnosis, kidney replacement therapy (KRT) modality, time to initiation of KRT, primary vascular access used, and time to receive a kidney transplant. Four of six Irish hospital groups participated in the study. A total of 38 patients were identified as Irish Travellers with KFRT, with a crude prevalence rate of KFRT of 0.12% (CI 0.084-0.161, 95%) or 11.9 per 10,000 Irish Travellers. The mean age for diagnosis of kidney disease was 43 (SD, 20.8) and at commencement of KRT was 45 (SD, 20.9) years. A biopsy-proven diagnosis was provided in 24%. Twenty-two per cent was diagnosed with polycystic kidney disease or congenital anomalies of the kidney and urinary tract. The predominant modality for KRT was haemodialysis (89%), with central venous catheters being the most common initial vascular access (79%). Kidney transplants occurred in 45% of those studied, with a mean waiting time of 1.96 (SD, 1.6) years. The Irish Traveller community have similar prevalence of KFRT when compared to the national prevalence, with a short time interval from diagnosis to commencement of KRT. They are less likely to avail of home therapies but have comparable wait times to the national waiting time to receive a kidney transplant.

Mechanistic Insights From Trials of Atrial Fibrillation Ablation: Charting a Course for the Future.

Success rates for catheter ablation of atrial fibrillation (AF), particularly persistent AF, remain suboptimal. Pulmonary vein isolation has been the cornerstone for catheter ablation of AF for over a decade. While successful for most patients, pulmonary vein isolation alone is still insufficient for a substantial minority. Frustratingly, multiple clinical trials testing a diverse array of additional ablation approaches have led to mixed results, with no current strategy that improves AF outcomes beyond pulmonary vein isolation in all patients. Nevertheless, this large collection of data could be used to extract important insights regarding AF mechanisms and the diversity of the AF syndrome. Mechanistically, the general model for arrhythmogenesis prompts the need for tools to individually assess triggers, drivers, and substrates in individual patients. A key goal is to identify those who will not respond to pulmonary vein isolation, with novel approaches to phenotyping that may include mapping to identify alternative drivers or critical substrates. This, in turn, can allow for the implementation of phenotype-based, targeted approaches that may categorize patients into groups who would or would not be likely to respond to catheter ablation, pharmacological therapy, and risk factor modification programs. One major goal is to predict individuals in whom additional empirical ablation, while feasible, may be futile or lead to atrial scarring or proarrhythmia. This work attempts to integrate key lessons from successful and failed trials of catheter ablation, as well as models of AF, to suggest future paradigms for AF treatment.

Unraveling the Mechanisms Behind the Short-Term Effects of Dry Needling: New Insights From a Mediation Analysis With Repeatedly Measured Mediators and Outcomes

ObjectiveTo explore the causal pathways underlying the short-term effects of deep dry needling (DDN) in people with chronic neck pain. DesignExplanatory longitudinal mediation analysis with repeatedly measured mediators and outcomes. SettingPrimary care setting. ParticipantsPatients (N=128) with chronic neck pain. InterventionsParticipants were randomized into 2 groups; DDN of the neck muscles combined with stretching (n=64) and stretching alone (n=64). Main Outcome MeasuresTwo outcomes (pain intensity and neck pain–related disability) and 3 candidate mediators (local pressure pain thresholds [PPTs], cervical range of motion [ROM], and neck muscle strength) were included. Pain intensity was also included as a competing mediator in the mediation analysis for disability. Mediators and outcomes were measured at 3 time points: after intervention and at 2- and 4-week follow-up. Age, sex, and the baseline values of the outcome and mediators were included as pretreatment mediator-outcome confounders. ResultsReductions in pain intensity strongly mediated the short-term effects of DDN on disability, from after intervention to 4-week follow-up. In addition, the attenuation of local hypersensitivity (via increasing PPTs) moderately mediated reductions in pain intensity at each time point. On the other hand, gains in cervical ROM contributed to reducing neck pain–related disability. Changes in muscle strength did not lead to better outcomes. ConclusionsThis novel study demonstrated that DDN effect on neck pain–related disability is strongly driven by the analgesic effects of this physical therapy modality. Increasing PPTs and cervical ROM seem to be also part of the mechanisms behind DDN's effect.