Therapy Treatment Research Articles

Nomogram for the prediction of infected pancreatic necrosis in moderately severe and severe acute pancreatitis.

As a serious complication of moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP), infected pancreatic necrosis (IPN) can lead to a prolonged course of interventional therapy. Most predictive models designed to identify such patients are complex or lack validation. The aim of this study was to develop a predictive model for the early detection of IPN in MSAP and SAP. A total of 594 patients with MSAP or SAP were included in the study. To reduce dimensionality, least absolute shrinkage and selection operator regression analysis was used to screen potential predictive variables, a nomogram was then constructed using logistic regression analysis. The receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the discrimination, accuracy, and clinical efficacy of the model. External data were also obtained to further validate the constructed model. There were 476, 118, and 82 patients in the training, internal validation, and external validation cohorts, respectively. Platelet count, hematocrit, albumin/globulin, severity of acute pancreatitis, and modified computed tomography severity index score were independent factors for predicting IPN in MSAP and SAP. The area under the ROC curves were 0.923, 0.940, and 0.817, respectively, in the three groups. There was a good consistency between the actual probabilities and the predicted probabilities. DCA revealed excellent clinical utility. The constructed nomogram is a simple and feasible model that has good clinical predictive value and efficacy in clinical decision-making for IPN in MSAP and SAP.

#1387 Comprehensive evaluation of clinical consequences in diverse forms of fistula elevation procedure

Abstract Background and Aims Arteriovenous fistula (AVF) superficialization is a recommended alternative autologous vascular access (VA) in patients for whom conventional AVF creation is not possible because of insufficient forearm vessels. This procedure utilizes a deeply located vein as an outflow conduit in AVF creation and makes the vein accessible for cannulation. Tunnel transposition (TT) is employed in a standard manner as a venous superficialization technique. This is accomplished by tunneling the transected vein through a subcutaneous tunnel. However, TT is frequently associated with stenosis at the area of transposition because the transposed vein is torsed, kinked, or compressed by external tissue. Thus, TT tends to be exclusively applied to the basilic vein in the upper arm considering both the anatomic positional relation and the inherent limitations of this procedure. We recently reported that elevation transposition (ET) can serve as a practical substitute for TT (Contrib Nephrol. 2019:198:1-11). ET is a simplified minimally invasive superficialization approach in which the vein is elevated and positioned in a subcutaneous pocket immediately beneath the incision. In AVF superficialization employing ET (i.e., fistula elevation procedure [FEP]), three potential outflow veins are available in the upper arm: the cephalic, basilic, and brachial veins. This study was performed to comprehensively evaluate the clinical consequences of three valid FEP techniques to ascertain whether they are reasonable alternatives to autologous VA and which, if any, have superior performance. Method The demographic and outcome data of 111 patients who underwent the FEP from April 2016 to June 2023 were retrospectively collected and analyzed. The outcomes of the three fistula techniques were assessed and compared in terms of patency rates, requirements for VA intervention therapy (VAIVT), and complication rates. Results The mean follow-up period was 36.2 ± 20.1 (range, 1.3-80.8) months. The basilic, cephalic, and brachial vein-based FEP was performed in 63.1%, 23.4%, and 13.5% of cases, respectively. The overall cumulative primary and secondary patency rates were 76.2% and 98.2% at 1 year and 70.7% and 97.0% at 2 years, respectively. VAIVT was required in 32.4% of cases, and the patency rates at 1 and 2 years after VAIVT were 65.3% and 62.0%, respectively. There were no significant differences in these patency rates among the three FEP types. Minor complications such as lymphorrhea or epidermolysis occurred in only 4.5% of cases. Conclusion Our results suggest that the FEP provides three equivalently reliable options to accommodate the deeply located venous anatomy of the upper arm on individual-patient basis. The diversity of the FEP may contribute to avoiding prosthetic VA and central venous catheter-based dialysis, at least in part, by expanding the applicability of the autologous VA.

1. Daily life in patients with hereditary transthyretin amyloidosis: a qualitative study

Topic: Patient Reported Outcomes/Quality of Life Background: Variant transthyretin amyloidosis (ATTRv) is a rare genetic disease that affects patients’ quality of life by affecting various organs and tissues. Despite a wealth of research on medical and psychosocial interventions, the impact of occupational therapy on patients with ATTRv is not well understood. This research focuses on the assessment of activities of daily living and occupations as a fundamental tool in the management of patients after diagnosis. Objective: The aim of this study was to develop an occupational therapy programme for the improvement of daily functioning and quality of life in patients with ATTRv. Methods: After an initial semi-structured interview, fourteen patients with ATTRv were enrolled in the study. The occupational therapist worked with the patient to develop short- and medium-term occupational goals, based on the Model of Human Occupation. During the six-month intervention period, weekly or ten-day sessions were held to monitor and adjust the guidelines. Outcomes were measured using scores for activities of daily living and psychological well-being. Results: The results showed that twelve patients stayed the same in their activities of daily living, two got worse and eight improved their psychological scores and the occupational situation. The study highlights the importance of early intervention and further research into the effectiveness of occupational therapy interventions for patients with ATTRv. It also notes that patients who received occupational therapy intervention reported that 6 months was not enough and emphasizes the fundamental role of the therapist in providing motivation, facilitating meaningful activities, improving daily living and routines.

Restoration of normal central pain processing following manual therapy in nonspecific chronic neck pain.

To determine if a 4-week manual therapy treatment restores normal functioning of central pain processing mechanisms in non-specific chronic neck pain (NSCNP), as well as the existence of a possible relationship between changes in pain processing mechanisms and clinical outcome. Cohort study. Sixty-three patients with NSCNP, comprising 79% female, with a mean age of 45.8 years (standard deviation: 14.3), received four treatment sessions (once a week) of manual therapy including articular passive mobilizations, soft tissue mobilization and trigger point treatment. Pressure pain thresholds (PPTs), conditioned pain modulation (CPM) and temporal summation of pain (TSP) were evaluated at baseline and after treatment completion. Therapy outcome was measured using the Global Rating of Change Scale (GROC), the Neck disability Index (NDI), intensity of pain during the last 24 hours, Tampa Scale of Kinesiophobia (TSK) and Pain Catastrophizing Scale (PCS). Two sets of generalized linear mixed models with Gaussian response and the identity link were employed to evaluate the effect of the intervention on clinical, psychological and psychophysical measures and the association between psychophysical and clinical outcomes. Following treatment, an increased CPM response (Coefficient: 0.89; 95% credibility interval = 0.14 to 1.65; P = .99) and attenuated TSP (Coefficient: -0.63; 95% credibility interval = -0.82 to -0.43; P = 1.00) were found, along with amelioration of pain and improved clinical status. PPTs at trapezius muscle on the side of neck pain were increased after therapy (Coefficient: 0.22; 95% credibility interval = 0.03 to 0.42; P = .98), but not those on the contralateral trapezius and tibialis anterior muscles. Only minor associations were found between normalization of TSP/CPM and measures of clinical outcome. Clinical improvement after manual therapy is accompanied by restoration of CPM and TSP responses to normal levels in NSCNP patients. The existence of only minor associations between changes in central pain processing and clinical outcome suggests multiple mechanisms of action of manual therapy in NSCNP.

#1118 Direct delivery of novel gene therapy to podocytes enables pathway to clinical translation for the treatment of glomerular diseases

Abstract Background and Aims Adeno associated vector (AAV) gene therapy has the potential to treat a wide range of kidney diseases via the targeted delivery of genes to kidney cells to repair cellular and renal function. Despite the potential to impact many kidney conditions, kidney AAV gene therapy has proven challenging due to technical and physiological hurdles limiting the ability of AAV to be effectively delivered to podocytes. We have developed a novel AAV gene therapy, PS-001, and local method of administration, to effectively and safely deliver the podocin gene NPHS2 to podocytes. Biallelic NPHS2 mutations are the most common cause of monogenic childhood nephrotic syndrome. Curative efficacy and resolution of disease phenotype was demonstrated in transgenic murine models following PS-001 gene therapy treatment. The potential for translation of this approach to NPHS2 nephropathy patients in the clinic was also demonstrated in pre-clinical studies in Gottingen Minipigs. Method Transgenic murine models representative of NPHS2-driven nephropathy were treated with an AAV gene therapy encoding NPHS2, including a knock in mouse model (Nphs2R140Q/−) which introduces a R140Q mutation in the podocin gene. Mice were assessed for improvement in disease phenotype via analysis of proteinuria, serum albumin, renal histopathology and survival. Mice were treated with an analogue of PS-001, as the PS-001 capsid is not permissive in rodents. Gottingen minipigs were treated with PS-001 and followed for 4 weeks. Clinically relevant doses and a procedure for local administration specifically to the kidney were established. In-life safety assessments from blood and urine were monitored and at study end pig tissues were assessed for podocin biodistribution using multiple assays (qPCR, RT-qPCR, ELISA, RNAScope and IF) and for toxicological effects via histopathological analysis. Results Using our AAV gene therapy platform, which includes a capsid that is highly effective at transducing human podocytes and promoter that drives gene expression specifically in the podocyte, the gene therapy product PS-001 encoding NPHS2 was generated. Using a murine analogue of PS-001, in vivo proof of concept studies in a translationally relevant murine disease model (Nphs2R140Q/−) showed NPHS2 delivery and podocin expression in glomeruli and efficacy in terms of renal function rescue. This was demonstrated by resolution of severe proteinuria (mean ACR ug/mg 6049 ± 2803 vs 192 ± 51 in PS-001 treated animals, n = 11), improved serum albumin (g/L 27.50 ± 3.33 g/L vs 30.75 ± 2.46 in PS-001 treated animals, P = .021) and reduction in glomerulosclerosis (mean sclerosed glomeruli 81% ± 19 vs 18.75% ± 12 in PS-001 treated animals, P < .0001). The methods to translate the approach to the clinical setting using a local administration were established in pigs. Administration of PS-001 resulted in transgene mRNA expression across 89% ± 11% of kidney glomeruli as assessed by RNAScope (n = 3 pigs), and transgene derived podocin could be specifically detected in podocytes as assessed by IF analysis. Using qPCR, RT-PCR and ELISA it was shown that using local administration, podocin gene expression was restricted exclusively to the kidney glomerulus, with gene expression undetectable in off-target organs including the liver. Additional toxicological assessments of renal and other organ function from urine and blood, and post-study histopathological assessments revealed no pre-clinical treatment-related safety concerns. Conclusion We present data showing development of an AAV gene therapy and method of administration for the delivery of transgenes specifically to podocytes. We have shown transgenes can be efficiently targeted to podocytes to replace defective genes or to use the podocyte as a protein factory to modulate glomerular biology. This technology therefore provides an important novel modality for potentially treating a broad range of glomerular disease. PS-001 is being developed as a novel approach to treat steroid resistant nephrotic syndrome caused by mutated NPHS2, and may become the first podocyte targeted gene therapy to enter clinical development.

Exploring the effect on primary endpoints in trials testing targeted therapy interventions for rheumatoid arthritis: a meta-epidemiological study on the appropriate use of a core outcome set

ObjectivesTo explore which core domain is best associated with the American College of Rheumatology (ACR) 20% response in trials assessing the effect of targeted interventions in rheumatoid arthritis (RA).MethodsA meta-epidemiological...

Evaluation of the Efficacy of Transcatheter Intervention, Surgery, and Pharmacological Treatment of Functional Mitral Regurgitation — A Bayesian Network Meta-Analysis with ≥12-Month Follow-up

Aim: Evaluate, using a Bayesian network meta-analysis system, the long-term prognosis of patients with functional mitral regurgitation (FMR) undergoing individual or combined treatment with percutaneous intervention, surgical intervention, or optimal medical therapy. Compare the prognostic outcomes of the different treatment modalities. Methods: Computerized searches of Embase, PubMed, and the Cochrane Library databases were performed. Randomized controlled trials (RCTs) and observational studies were searched to compare prognoses following transcatheter interventions, surgery, and optimal pharmacological treatment for FMR, all with a construction timeframe of 21 October 2023. The primary endpoint event was all-cause mortality. The secondary endpoint events were heart failure readmission rate, mitral regurgitation (MR) ≤2+ improvement rate, New York Heart Association (NYHA) improvement rate (improvement to I–II), and degree of left ventricular ejection fraction (LVEF) improvement. Results: Twenty-six (26) papers were included, comprising 10 RCTs and 16 observational studies involving 5443 patients. A network meta-analysis showed no significant difference in prognosis for all-cause mortality among transcatheter interventions, surgical procedures, and optimal pharmacological treatments. For heart failure readmission rates, mitral valve surgery was superior to MitraClip (odds ratio (OR) = 11.82; 95% confidence interval (CI): 1.67, 90.13). For NYHA (improvement to I–II) improvement rates, the results showed no significant differences for the various mitral interventions. For MR ≤2+ improvement rates, the MitraClip (OR = 3.07; 95% CI: 2.42, 3.76), MitraClip+Guideline-directed medical therapy (GDMT) (OR = 2.93; 95% CI: 2.38, 3.52), mitral valve surgery (OR = 3.01; 95% CI: 2.24, 3.8), and annuloplasty (OR = 4.31; 95% CI: 3.12, 5.58) were superior to GDMT, and mitral valve surgery (OR = 0.07; 95% CI: –0.45, 0.62) was superior to MitraClip+GDMT. For the degree of improvement in LVEF, Carillon+GDMT (mean difference (MD) = –0.97; 95% CI: –1.72, –0.22) was superior to GDMT, mitral valve surgery was superior to Carillon+GDMT (MD = 4.67; 95% CI: 0.92, 8.39); MitraClip+GDMT (MD = 4.01; 95% CI: 1.28, 6.66), GDMT (MD = 3.71; 95% CI: 0.04, 7.35), and annuloplasty were superior to mitral valve surgery (MD = –6.42; 95% CI: –11.96, –0.78). Conclusion: There were no significant differences among the three treatment modalities of transcatheter intervention, surgery, and optimal drug therapy in improving all-cause mortality hard endpoint events, and no significant differences were seen in the rates of heart failure readmission and NYHA improvement (improvement to I–II). However, surgery was superior to transcatheter intervention and optimal drug therapy in terms of improvement in the degree of regurgitation and LVEF.

Geriatric ophthalmologic co-management : A case report of interdisciplinary collaboration

This case report details the assessment and interdisciplinary collaboration in the management of an 81-year-old patient presenting with acute visual impairment, dizziness, general weakness, gait disturbances and fear of falling. A holistic geriatric evaluation revealed orthostatic dysregulation and an underlying multifactorial gait disorder exacerbated by visual impairment. Ophthalmological findings included left central retinal artery branch occlusion and cataracts. A comprehensive geriatric assessment showed frailty, impaired mobility and decreased functional abilities. Subsequent patient-centered interdisciplinary approaches included treatment for retinal ischemia, orthostatic testing, medication reconciliation, physiotherapy and occupational therapy. This case emphasizes how interdisciplinary collaboration between ophthalmology and geriatrics enables proactive assessment and intervention to reduce the risk of functional decline and loss of autonomy in visually impaired patients, which is of particular relevance considering the increasing prevalence of visual impairment in the ageing population.

Advances in non-coding RNA in tendon injuries

Tendons serve as important weight-bearing structures that smoothly transfer forces from muscles to skeletal parts, allowing contracted muscle movements to be translated into corresponding joint movements. For body mechanics, tendon tissue plays an important role. If the tendons are damaged to varying degrees, it can lead to disability or pain in patients. That is to say, tendon injuries havea significant impact on quality of life and deserve our high attention. Compared to other musculoskeletal tissues, tendons are hypovascular and hypo-cellular, and therefore have a greater ability to heal, this will lead to a longer recovery period after injury or even disability, which will significantly affect the quality of life. There are many causes of tendon injury, including trauma, genetic factors, inflammation, aging, and long-term overuse, and the study of related mechanisms is of great significance. Currently, tendon there are different treatment modalities, like injection therapy and surgical interventions. However, they have a high failure rate due to different reasons, among which the formation of adhesions severely weakens the tissue strength, affecting the functional recovery and the patient’s quality of life. A large amount of data has shown that non coding RNAs can play a huge role in this field, thus attracting widespread attention from researchers from various countries. This review summarizes the relevant research progress on non-coding RNAs in tendon injuries, providing new ideas for a deeper understanding of tendon injuries and exploring new diagnostic and therapeutic approaches.

Hyperbaric oxygen therapy vs. pharmacological intervention in adults with fibromyalgia related to childhood sexual abuse: prospective, randomized clinical trial

Fibromyalgia syndrome (FMS) is a chronic pain syndrome characterized by disruptions in pain processing within the central nervous system. It exhibits a high prevalence among patients with a history of traumatic experiences, notably childhood sexual abuse (CSA). This study compared the efficacy of hyperbaric oxygen therapy (HBOT) to the current pharmacological standard of care for individuals suffering from CSA-related FMS. Forty-eight participants diagnosed with FMS and a history of CSA were randomly assigned to either the HBOT group (60 sessions of 100% oxygen at 2 ATA for 90 min, with air breaks every 5 min) or the medication (MED) group (FDA-approved medications, Pregabalin and Duloxetine). The primary endpoint was the Fibromyalgia impact questionnaire (FIQ) score, while secondary endpoints encompassed emotional status and daily functioning questionnaires, as well as pain thresholds and conditioned pain modulation tests. Brain activity was evaluated through single photon emission computed tomography (SPECT). Results revealed a significant group-by-time interaction for the FIQ score favoring HBOT over MED (p < 0.001), with a large effect size (Cohen's d = − 1.27). Similar findings were observed in emotional symptoms and functional measures. SPECT imaging demonstrated an increase in activity in pre-frontal and temporal brain areas, which correlated with symptoms improvement. In conclusion, HBOT exhibited superior benefits over medications in terms of physical, functional, and emotional improvements among FMS patients with a history of CSA. This associated with increased activity in pre-frontal and temporal brain areas, highlighting the neuroplasticity effect of HBOT.

Efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy in hematologic malignancies: a living systematic review (protocol)

Objective To determine the efficacy and safety of CAR-T therapy in the treatment of patients with hematologic malignancies, in comparison with other current therapies. Design A living systematic review Methods We will include randomized trials evaluating the effect of CAR-T therapy versus other active treatments, hematopoietic stem cell transplantation, best supportive care or any other intervention in patients with hematologic malignancies. Non-randomized primary studies will be searched in case we found no direct evidence from randomized controlled trials. Two reviewers will independently screen each study for eligibility, extract data, and assess the risk of bias. Efficacy measures will include overall survival rate, overall response rate, complete response/remission (CR) rate, partial response/remission (PR) rate, relapse from CR, progression-free survival, and time from CAR-T infusion to transplantation. Safety measures will include serious adverse events, the incidence of cytokine release syndrome, graft-versus-host disease, neurotoxicity, and total adverse events. Quality of life will also be assessed. Meta-analyses will be carried out to summarize the results. We will apply the GRADE approach to assess the certainty of the evidence for each outcome. A living, web-based version of this review will be openly available until there is solid evidence to respond to the review objective. We will resubmit it for publication every time the conclusions change or whenever there are substantial updates.

Amphiphilic AIE Fluorescent Probe: A Dual-Functionality Strategy for Efficient Antibacterial Therapy Fluorescence Bioimaging against Staphylococcus aureus.

Drug-resistant bacteria present a grave threat to human health. Fluorescence imaging-guided photodynamic antibacterial therapy holds enormous potential as an innovative treatment in antibacterial therapy. However, the development of a fluorescent material with good water solubility, large Stokes shift, bacterial identification, and high photodynamic antibacterial efficiency remains challenging. In this study, we successfully synthesized an amphiphilic aggregation-induced emission (AIE) fluorescent probe referred to as NPTPA-QM. This probe possesses the ability to perform live-bacteria fluorescence imaging while also exhibiting antibacterial activity, specifically against Staphylococcus aureus (S. aureus). We demonstrate that NPTPA-QM can eliminate S. aureus at a very low concentration (2 μmol L-1). Moreover, it can effectively promote skin wound healing. Meanwhile, this NPTPA-QM exhibits an excellent imaging ability by simple mixing with S. aureus. In summary, this research presents a straightforward and highly effective method for creating "amphiphilic" AIE fluorescent probes with antibacterial properties. Additionally, it offers a rapid approach for imaging bacteria utilizing red emission.

Growth Patterns of the Maxillomandibular Complex in Preadolescent Patients With Pierre-Robin Sequence Using Cluster Analysis and Longitudinal Follow-Up Cephalometric Data.

To investigate the growth patterns of the maxillomandibular complex in preadolescent patients with Pierre-Robin sequence (PRS). The samples consisted of 20 preadolescent PRS patients who had cleft palate and did not undergo growth-modification therapy or surgical intervention [6 boys and 14 girls; mean age of lateral cephalograms taken, 8.8 y (T1) and 13.7y (T2)]. According to k-means cluster analysis, four clusters were defined over 3 major groups at T1: (1) Both very retrusive maxilla and mandible group: Cluster-4 [n=4, very large gonial angle, very low facial height ratio (FHR)] and Cluster-1 (n=5, small gonial angle, normal FHR); (2) Retrusive maxilla and very retrusive mandible group (Cluster-3, n=7, normal gonial angle, very low FHR); and (3) Both normal maxilla and mandible group (Cluster-2, n=4, very large gonial angle, low FHR). Seven angular and ratio variables [sella-nasion-A point (SNA), sella-nasion-B point (SNB), A point-nasion-B point (ANB), saddle angle, gonial angle, mandibular-body-length/anterior-cranial-base-length (MBL/ACBL), and FHR] at T1 and T2 and growth change from T1 to T2 were investigated. At T1, SNA, SNB, saddle angle, gonial angle (all P<0.05), and FHR (P<0.01) showed significant difference among 4 clusters. At T2, SNA, SNB and gonial angle (all P<0.05) still showed significant difference among 4 clusters. During T1 to T2, there was no significant change in variables at each cluster except an increase in MBL/ACBL in Cluster-1 and FHR in Cluster-3 (all P<0.05). Preadolescent PRS patients exhibited diverse skeletal phenotypes at T1, which did not change significantly from their original skeletal patterns by growth during T1 to T2.

Biological dose optimization incorporating intra-tumoural cellular radiosensitivity heterogeneity in ion-beam therapy treatment planning

Objective. Treatment plans of ion-beam therapy have been made under an assumption that all cancer cells within a tumour equally respond to a given radiation dose. However, an intra-tumoural cellular radiosensitivity heterogeneity clearly exists, and it may lead to an overestimation of therapeutic effects of the radiation. The purpose of this study is to develop a biological model that can incorporate the radiosensitivity heterogeneity into biological optimization for ion-beam therapy treatment planning. Approach. The radiosensitivity heterogeneity was modeled as the variability of a cell-line specific parameter in the microdosimetric kinetic model following the gamma distribution. To validate the developed intra-tumoural-radiosensitivity-heterogeneity-incorporated microdosimetric kinetic (HMK) model, a treatment plan with H-ion beams was made for a chordoma case, assuming a radiosensitivity heterogeneous region within the tumour. To investigate the effects of the radiosensitivity heterogeneity on the biological effectiveness of H-, He-, C-, O-, and Ne-ion beams, the relative biological effectiveness (RBE)-weighted dose distributions were planned for a cuboid target with the stated ion beams without considering the heterogeneity. The planned dose distributions were then recalculated by taking the heterogeneity into account. Main results. The cell survival fraction and corresponding RBE-weighted dose were formulated based on the HMK model. The first derivative of the RBE-weighted dose distribution was also derived, which is needed for fast biological optimization. For the patient plan, the biological optimization increased the dose to the radiosensitivity heterogeneous region to compensate for the heterogeneity-induced reduction in biological effectiveness of the H-ion beams. The reduction in biological effectiveness due to the heterogeneity was pronounced for low linear energy transfer (LET) beams but moderate for high-LET beams. The RBE-weighted dose in the cuboid target decreased by 7.6% for the H-ion beam, while it decreased by just 1.4% for the Ne-ion beam. Significance. Optimal treatment plans that consider intra-tumoural cellular radiosensitivity heterogeneity can be devised using the HMK model.

Estimating scenarios for survival time in patients with advanced melanoma receiving immunotherapy and targeted therapy.

We aim to provide survival scenario estimates for patients with advanced melanoma starting targeted therapies and immunotherapies. We sought randomized trials of targeted therapies and immunotherapies for advanced melanoma and recorded the following percentiles (represented survival scenario) from each overall survival (OS) curve: 90th (worst-case), 75th (lower-typical), 50th (median), 25th (upper-typical), and 10th (best-case). We tested whether these scenarios can be estimated for each OS curve by multiplying its median by 4 multiples: 0.25 (worst-case), 0.5 (lower-typical), 2 (upper-typical), and 3 (best-case). We identified 15 trials with 8025 patients. For first-line combination targeted therapy treatment groups, the median (interquartile range, IQR) in months for each percentile was: 90th, 6.2 (6.0-6.5); 75th, 11.3 (11.3-11.4); and median, 24.4 (23.5-25.3). For the first-line combination immunotherapy treatment group, the percentiles in months were: 90th, 3.9 (2.8-4.5); 75th, 13.4 (10.1-15.4), median 73 (not applicable). In targeted therapy groups, simple multiples of the median OS were accurate for estimating the 90th percentile in 80%; 75th percentile in 40%; 25th percentile in 100%. In immunotherapy groups, these multiples were accurate at 0% for the 90th percentile, and 43% for the 75th percentile. The 90th percentile (worst-case scenario) was better estimated as 1/6× median OS, and the 75th percentile (lower-typical) as 1/3× median OS. Simple multiples of the median OS are a useful framework to estimate scenarios for survival for patients receiving targeted therapies, not immunotherapy. Longer follow-up is required to estimate upper-typical and best-case scenarios.

Radiologically guided interventional therapies for the treatment of neuroendocrine tumors

The majority of patients with neuroendocrine tumors (NET) develop liver metastases during the course of the disease, significantly impacting prognosis and quality of life. Radiologically guided interventional therapies, such as thermal ablation, transarterial embolization (TAE)/chemoembolization (TACE), and selective internal radiotherapy (TARE), can play acrucial role in the treatment of metastatic NET. Due to the rarity of the disease, the majority of evidence is based on retrospective studies. For thermal ablation, the complete response rates ranging from 31.6to 95.3% depending on the study. No significant differences in outcomes were found between TAE, TACE, and TARE. In several studies, all intra-arterial procedures led to areduction of tumor-related symptoms and achieved disease control. Thermal ablation can be used as acurative therapy in oligometastatic patients with nonresectable liver metastases from NETs. In cases of disseminated liver metastases, intra-arterial therapy using TAE, TACE, or TARE can be employed.

Treatment of portal hypertension complicated by variceal bleeding

Background. Mortality in variceal bleeding (VB) on the background of portal hypertension (PH) is highest among patients with gastrointestinal bleeding. The treatment of PH complicated by VB is a complex problem that is far from being solved, especially in case of Child-Pugh class B and C decompensation. The aim of the study was to determine the causes of PH complicated by VB, features of conservative and interventional therapy, indications and nature of surgical procedures, treatment efficacy, as well as causes of complications and mortality. Materials and methods. We analyzed treatment outcomes of 923 inpatients with PH complicated by VB who were treated in the clinic of the Department of Surgery of the Faculty of Dentistry of Bogomolets National Medical University on the basis of the Kyiv City Clinical Emergency Hospital from 2012 to 2023. It was possible to talk about the cause of PH based on anamnestic data in 61 % of cases. In 711 (77 %) patients, the source of bleeding was detected endoscopically within 30–60 minutes from the moment of admission to the clinic. Conservative therapy included the administration of hemostatic and agents lowering pressure in the portal system, as well as vasoconstrictors that reduce portal blood flow. For the failure of conservative therapy, unstable hemostasis, and repeated previous bleedings, 59 (6.4 %) patients were operated. The methodology of the research analysis consisted in the fact that the arithmetic mean and standard error (M ± m) were determined as the characteristics of the groups for features with a distribution corresponding to the Gaussian law. This reference method of descriptive statistics was applied to evaluate surgical treatment in comparison with conservative therapy and interventional measures. Results. Endoscopic hemostasis by the ligature method was achieved in 97 (10.5 %) patients. Repeated endoscopy due to VB recurrence was done in 276 (29.9 %) participants. In cases of unsatisfactory endoscopic hemostasis, as well as recurrent VB, a Sengstaken-Blakemore probe was installed. In case of right-sided PH, the formation of varices in the esophagus is caused by the discharge of blood mainly through the coronary vein, which required its transection during еsophagogastric devascularization. In compliance with this rule, the patients underwent esophagogastric devascularization, circular transection of the esophagus, which provided portoazygous disconnection. The total mortality rate was 43.1 %, among operated people — 8.5 %, and among non-operated ones — 42.1 %. Conclusions. PH complicated by VB is evidence of decompensated processes in the liver parenchyma or obstruction in the portal system. Conservative therapy and interventional measures make it possible to stop bleeding and prepare the patient for elective surgery, if necessary. An operation that stops blood flow through dilated veins of the esophagus or stomach is an effective method of treating bleeding in portal hypertension.

A Cost–Consequence Analysis of Nutritional Interventions Used in Hospital Settings for Older Adults with or at Risk of Malnutrition

Background: Malnutrition is a significant and prevalent issue in hospital settings, associated with increased morbidity and mortality, longer hospital stays, higher readmission rates, and greater healthcare costs. Despite the potential impact of nutritional interventions on patient outcomes, there is a paucity of research focusing on their economic evaluation in the hospital setting. This study aims to fill this gap by conducting a cost–consequence analysis (CCA) of nutritional interventions targeting malnutrition in the hospital setting. Methods: We performed a CCA using data from recent systematic reviews and meta-analyses, focusing on older adult patients with or at risk of malnutrition in the hospital setting. The analysis included outcomes such as 30-day, 6-month, and 12-month mortality; 30-day and 6-month readmissions; hospital complications; length of stay; and disability-adjusted life years (DALYs). Sensitivity analyses were conducted to evaluate the impact of varying success rates in treating malnutrition and the proportions of malnourished patients seen by dietitians in SingHealth institutions. Results: The CCA indicated that 28.15 DALYs were averted across three SingHealth institutions due to the successful treatment or prevention of malnutrition by dietitians from 1 April 2021 to 31 March 2022, for an estimated 45,000 patients. The sensitivity analyses showed that the total DALYs averted ranged from 21.98 (53% success rate) to 40.03 (100% of malnourished patients seen by dietitians). The cost of implementing a complex nutritional intervention was USD 218.72 (USD 104.59, USD 478.40) per patient during hospitalization, with additional costs of USD 814.27 (USD 397.69, USD 1212.74) when the intervention was extended for three months post-discharge and USD 638.77 (USD 602.05, USD 1185.90) for concurrent therapy or exercise interventions. Conclusion: Nutritional interventions targeting malnutrition in hospital settings can have significant clinical and economic benefits. The CCA provides valuable insights into the costs and outcomes associated with these interventions, helping healthcare providers and policymakers to make informed decisions on resource allocation and intervention prioritization.

Available Therapeutic Options for Corneal Neovascularization: A Review

Corneal neovascularization can impair vision and result in a poor quality of life. The pathogenesis involves a complex interplay of angiogenic factors, notably vascular endothelial growth factor (VEGF). This review provides a comprehensive overview of potential therapies for corneal neovascularization, covering tissue inhibitors of metalloproteinases (TIMPs), transforming growth factor beta (TGF-β) inhibitors, interleukin-1L receptor antagonist (IL-1 Ra), nitric oxide synthase (NOS) isoforms, galectin-3 inhibitors, retinal pigment epithelium-derived factor (PEDF), platelet-derived growth factor (PDGF) receptor inhibitors, and surgical treatments. Conventional treatments include anti-VEGF therapy and laser interventions, while emerging therapies such as immunosuppressive drugs (cyclosporine and rapamycin) have been explored. Losartan and decorin are potential antifibrotic agents that mitigate TGF-β-induced fibrosis. Ocular nanosystems are innovative drug-delivery platforms that facilitate the targeted release of therapeutic agents. Gene therapies, such as small interfering RNA and antisense oligonucleotides, are promising approaches for selectively inhibiting angiogenesis-related gene expression. Aganirsen is efficacious in reducing the corneal neovascularization area without significant adverse effects. These multifaceted approaches underscore the corneal neovascularization management complexity and highlight ideas for enhancing therapeutic outcomes. Furthermore, the importance of combination therapies and the need for further research to develop specific inhibitors while considering their therapeutic efficacy and potential adverse effects are discussed.

Influence of Music Therapy on the Improvement of Perceived Well-Being Indices in Women with Breast Cancer Undergoing Hormonal Treatment

ABSTRACT Background Although there are a growing number of studies investigating the benefits of music therapy interventions with patients diagnosed with cancer, few studies have taken an approach that specifically examines indices of perceived well-being in women with breast cancer. Overcoming these challenges can be an important step in the recovery process. Purpose The purpose of our study was to know the positive influence of responsive music therapy through gong sounds, emitted live, on different areas of well-being of women with breast cancer. Methods Four individual sessions of responsive music therapy with live gong sounds were conducted in which three women (M = 54; SD = 5.57) participated both in the music therapy program and in the completion of the Functional Assessment of Cancer Therapy – Breast (FACT-B) and a semi-structured interview with ad hoc designed questions about perception of qualitative aspects. Results The results showed that the music therapy sessions significantly improved, p = .043 < 0.05, various domains of perceived well-being in women with breast cancer. Discussion This article highlights several key benefits associated with music therapy and various indices of well-being in women with breast cancer, identifies the limitations of the study, and discusses the findings. It is considered necessary to replicate this practice in future studies that include a larger sample and age range over longer follow-up periods. Translation for Health Education Practice The text highlights the importance of considering music therapy as a complementary intervention in comprehensive cancer care programs, which may be relevant to health educators when considering intervention and support approaches for cancer patients. Health education interventions targeting the enhancement of cancer patients’ well-being should incorporate music therapy techniques.