Dose Of Therapy Research Articles

DOTATATE PET/MR Imaging Differentiates Secondary-Progressive from de Novo World Health Organization Grade 3 Meningiomas.

WHO grade 3 meningiomas are rare and poorly understood and have a higher propensity for recurrence, metastasis, and worsened clinical outcomes compared with lower-grade meningiomas. The purpose of our study was to prospectively evaluate the molecular profile, PET characteristics, and outcomes of patients with World Health Organization grade 3 meningiomas who were imaged with gallium 68 (68Ga) DOTATATE PET/MR imaging. Patients with World Health Organization grade 3 meningiomas enrolled in our prospective observational cohort evaluating the utility of (68Ga) DOTATATE PET/MR imaging in somatostatin receptor positive brain tumors were included. We stratified patients by de novo-versus-secondary-progressive status and evaluated the differences in the PET standard uptake value, molecular profiles, and clinical outcomes. Patients met the inclusion criteria (secondary-progressive: 7/14; de novo: 7/14). The secondary-progressive cohort had a significantly higher per-patient number of surgeries (4.1 versus 1.6; P = .011) and trended toward a higher number of radiation therapy courses (2.4 versus 1.6; P = .23) and cumulative radiation therapy doses (106Gy versus 68.3Gy; P = .31). The secondary-progressive cohort had a significantly lower progression-free survival compared with the de novo cohort (4.8 versus 37.7 months; P = .004). Secondary-progressive tumors had distinct molecular pathology profiles with higher numbers of mutations (3.5 versus 1.2; P = .024). Secondary-progressive tumors demonstrated higher PET standard uptake values (17.1 versus 12.4; P = .0021). Our study confirms prior work illustrating distinct clinical outcomes in secondary-progressive and de novo World Health Organization grade 3 meningiomas. Furthermore, our findings support (68Ga) DOTATATE PET/MR imaging as a useful management strategy in World Health Organization grade 3 meningiomas and provide insight into meningioma biology, as well as clinical management implications.

Diagnosis, Treatment and Long-Term Management of Vitamin B12 Deficiency in Adults: A Delphi Expert Consensus.

Background/Objectives: Vitamin B12 deficiency can cause variable symptoms, which may be irreversible if not diagnosed and treated in a timely manner. We aimed to develop a widely accepted expert consensus to guide the practice of diagnosing and treating B12 deficiency. Methods: We conducted a scoping review of the literature published in PubMed since January 2003. Data were used to design a two-round Delphi survey to study the level of consensus among 42 experts. Results: The panelists agreed on the need for educational and organizational changes in the current medical practices for diagnosing and treating B12 deficiency. Recognition of clinical symptoms should receive the highest priority in establishing the diagnosis. There is agreement that the serum B12 concentration is useful as a screening marker and methylmalonic acid or homocysteine can support the diagnosis. Patient lifestyle, disease history, and medications can provide clues to the cause of B12 deficiency. Regardless of the cause of the deficiency, initial treatment with parenteral B12 was regarded as the first choice for patients with acute and severe manifestations of B12 deficiency. The use of high-dose oral B12 at different frequencies may be considered for long-term treatment. Prophylactic B12 supplementation should be considered for specific high-risk groups. Conclusions: There is a consensus that clinical symptoms need to receive more attention in establishing the diagnosis of B12 deficiency. B12 laboratory markers can support the diagnosis. The severity of clinical symptoms, the causes of B12 deficiency, and the treatment goals govern decisions regarding the route and dose of B12 therapy.

Evaluation of the therapeutic efficacy of different doses of LT4 in pregnant women with high-normal TSH levels and TPOAb positivity in the first half of pregnancy.

The objective was to investigate the efficacy of different doses of levothyroxine therapy among pregnant women exhibiting high-normal thyroid stimulating hormone levels and positive thyroid peroxidase antibodies throughout the first half of pregnancy. Pregnant women exhibiting high-normal thyroid stimulating hormone levels and thyroid peroxidase antibodies positivity throughout the initial half of pregnancy were selected from January 2021 to September 2023. Based on the different doses of levothyroxine, the pregnant women were categorized into the nonintervention group (G0, 122 women), 25µg levothyroxine intervention group (G25, 69 women), and 50µg levothyroxine intervention group (G50, 58 women). Serum parameters, gastrointestinal symptoms, small intestinal bacterial overgrowth (SIBO), maternal and neonatal outcomes were compared after the intervention among the three groups. After the intervention, in the G25 and G50 groups, the thyroid stimulating hormone, triglyceride and low-density lipoprotein levels were notably less in contrast to those in the G0 group (P < 0.05). The rates of abdominal distension and SIBO in the G25 and G50 groups were notably lower in contrast to the G0 group (P = 0.043 and 0.040, respectively). The G50 group had a lower rate of spontaneous abortion and premature membrane rupture than the G0 group (P = 0.01 and 0.015, respectively). Before 11+ 2 weeks of gestation and at thyroid peroxidase antibodies levels ≥ 117 IU/mL, in contrast to the G0 group, the G50 group experienced a decreased rate of spontaneous abortion (P = 0.008). The G50 group had significantly higher newborn weight than the G0 group (P = 0.014), as well as a notably longer newborn length than the G0 and G25 groups (P = 0.005). For pregnant women with high-normal thyroid stimulating hormone levels and thyroid peroxidase antibodies positive during the first half of pregnancy, supplementation with 50µg levothyroxine was more effective in improving their blood lipid status and gastrointestinal symptoms, reducing the incidence of SIBO and premature rupture of membranes, and before 11+2 weeks, TPOAb ≥ 117IU/mL proved more beneficial in mitigating the risk of spontaneous abortion.

Effect of the timing of primary endodontic treatment and dosage of radiation therapy on the filling material removal.

This study investigated the effect of the timing of primary endodontic treatment and dosage of radiotherapy on the remaining filling material (RFM) during endodontic reintervention. 60 single-rooted human mandibular premolars were distributed into five groups (n = 12), according to the timing and dosage of radiation (55Gy or 70Gy): NegativeCG-non-irradiated teeth; Endo-pre-RT55/70-obturation before irradiation (55Gy or 70Gy); Endo-post-RT55/70-obturation and reintervention after irradiation (55Gy or 70Gy). Roots were cleaved and analysed under stereomicroscope and Scanning Electron Microscope to quantify (%) the RFM. Experimental groups had a significantly greater amount (p < 0.05) of RFM in the middle and apical thirds than the control group, except for Endo-pre-RT55 in the middle third (p < 0.0001). The apical third had greater amount of RFM (p < 0.05). Radiation therapy, before and after primary endodontic treatment, increased the amount of RFM, regardless of the dose delivered. When necessary, reintervention preferably must be performed before radiation therapy.

Safety and Efficacy of Inpatient Infliximab Rescue Therapy for Acute Crohn's Disease Flares.

Describe the safety, complications, and need for urgent surgery in patients requiring inpatient rescue infliximab for acute Crohn's disease (CD) flare. Infliximab is increasingly used for patients hospitalized with acute severe ulcerative colitis as rescue therapy; however, optimal management for patients hospitalized for CD flares remains unclear. A single-institution retrospective study of patients aged 18+ admitted from 2008 to 2020 with acute Crohn's flare requiring induction of rescue infliximab therapy. Outcomes included postoperative and medication-related complications and need for urgent surgery. 52 patients were included in analysis; 8% required surgery on index admission, and 19% required surgery within 90 days of infliximab. Postoperative complications included 1 anastomotic leak, 3 superficial wound infections, 3 prolonged ileus, and 1 urinary infection. There were no adverse reactions to infliximab infusion, and medical complication rates were low. Patients with penetrating disease were more likely to undergo surgery within 90 days of infliximab (43% vs 8%; P = .01). Mean LOS was longer for patients undergoing surgery within 90 days of therapy compared to those who did not (13.4 vs 8.3days, P = .04). Inpatient rescue infliximab is safe for treating acute Crohn's disease flare in addition to standard steroid therapy. The majority of patients hospitalized with Crohn's flare requiring rescue infliximab avoided surgery with low postoperative and medication-related complications. More research is needed to clarify the optimal rescue infliximab therapy dosage.

Unsupervised robot-assisted rehabilitation after stroke: feasibility, effect on therapy dose, and user experience

BackgroundUnsupervised robot-assisted rehabilitation is a promising approach to increase the dose of therapy after stroke, which may help promote sensorimotor recovery without requiring significant additional resources and manpower. However, the unsupervised use of robotic technologies is not yet a standard, as rehabilitation robots often show low usability or are considered unsafe to be used by patients independently. In this paper we explore the feasibility of unsupervised therapy with an upper limb rehabilitation robot in a clinical setting, evaluate the effect on the overall therapy dose, and assess user experience during unsupervised use of the robot and its usability.MethodsSubacute stroke patients underwent a four-week protocol composed of daily 45 min-sessions of robot-assisted therapy. The first week consisted of supervised therapy, where a therapist explained how to interact with the device. The second week was minimally supervised, i.e., the therapist was present but intervened only if needed. After this phase, if participants learnt how to use the device, they proceeded to two weeks of fully unsupervised training. Feasibility, dose of robot-assisted therapy achieved during unsupervised use, user experience, and usability of the device were evaluated. Questionnaires to evaluate usability and user experience were performed after the minimally supervised week and at the end of the study, to evaluate the impact of therapists’ absence.ResultsUnsupervised robot-assisted therapy was found to be feasible, as 12 out of the 13 recruited participants could progress to unsupervised training. During the two weeks of unsupervised therapy participants on average performed an additional 360 min of robot-assisted rehabilitation. Participants were satisfied with the device usability (mean System Usability Scale scores > 79), and no adverse events or device deficiencies occurred.ConclusionsWe demonstrated that unsupervised robot-assisted therapy in a clinical setting with an actuated device for the upper limb was feasible and can lead to a meaningful increase in therapy dose. These results support the application of unsupervised robot-assisted therapy as a complement to usual care in clinical settings and pave the way to its application in home settings.Trial registrationRegistered on 13.05.2020 on clinicaltrials.gov (NCT04388891).

In Vitro Investigation of the Antimicrobial Potential and Cell Viability of Different Dosages of Ozone Therapy

ABSTRACT The aim of the study was to evaluate and compare, in vitro, the cytotoxicity of different applied ozone dosages in keratinocyte (NOK) and fibroblast (L929) cell lines, as well as the antimicrobial potential for Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). NOK and L929 cells and strains of gram-positive bacteria S. aureus and gram-negative bacteria E. coli were divided into seven experimental groups: ozone at doses from 0, 0.005, 0.01, 0.02, 0.03, 0.04 and 0.05 mg/L. The effect of ozone on cell viability/cytotoxicity was determined using the alamarBlue® assay, the Live/Dead® assay and the morphometric analysis of the percentage of live and dead cells. The results show that applied ozone dosages of 0.005, 0.01 and 0.02 mg/L showed the highest viability values of NOK and L929 cells, as well as a higher density and percentage of live cells in the 72-hour experimental. However, no difference was observed in the percentage of dead cells between the experimental groups. Furthermore, ozone promoted a reduction in CFUs at all tested dosages. With the results obtained in the present study, it is possible to confirm the restorative potential of ozone therapy in a dose-dependent response, as well as its antimicrobial potential.

Abstract CT186: A first-in-human phase 1 dose-escalation and expansion study of intratumoral oncolytic reovirus (RC402) as a monotherapy or in combination with pembrolizumab in advanced solid tumors

Abstract Background: RC402 is an oncolytic reovirus that selectively infects and destroys cancer cells. Preclinical studies have shown that RC402 remodels the tumor immune microenvironments and elicits potent anti-tumor immunity, thereby enhancing immune checkpoint inhibitors. Methods: This Phase I clinical trial (ACTRN12620000777998) was designed to evaluate the safety profiles and antitumor efficacy of intratumoral (IT) RC402 in patients with advanced solid tumors refractory to standard therapy and with accessible tumor lesions for IT injection of RC402. For the dose-escalation part (Phase 1a), the RC402 monotherapy dose was evaluated at 3 dose levels in Part A and the RC402 combination therapy dose with pembrolizumab was evaluated at 2 dose levels in part B using an accelerated titration method followed by a standard 3+3 dose escalation. In the dose-expansion part (Phase 1b), patients were treated with IT RC402 in combination with pembrolizumab at the recommended dose selected from the dose escalation part. RC402 was IT injected on day 1 of each treatment cycle. Fixed-dose pembrolizumab (200mg Q3W) was intravenously administered on day 8 of each treatment cycle for Phase 1a Part B and Phase 1b. Viral shedding was assessed serially in serum, urine, sputum, and stool samples, and neutralizing antibodies to Reovirus Type 3 Dearing were analyzed in serum samples. Results: Nine patients (2 gastric cancer and 1 cutaneous squamous cell carcinoma [cSCC] in Phase 1a Part A, 1 cSCC and 1 colorectal cancer [CRC] in Phase 1a Part B, and 1 cSCC and 3 CRC in Phase 1b) were enrolled and treated with at least two doses of RC402. IT administration of RC402 was generally well tolerated with no dose-limiting toxicities at all dose levels (1.6 × 108, 1.4 × 109, and 1.4 ×1010 PFU) as a monotherapy or in combination with pembrolizumab. The maximum tolerated dose was not reached. There were no treatment-emergent adverse events (TEAEs) leading to treatment discontinuation and no RC402-related serious TEAEs. The most common AEs were chills, fatigue, injection site reactions (erythema and pain) and nausea. Response evaluation showed two complete responses (one patients with cSCC in Phase 1a Part A and another patient with cSCC in the dose expansion part) lasting longer than 90 weeks and 36 weeks, respectively. No viral shedding was detected in any serum, urine, sputum, and stool samples on days 1, 2, and 15 of cycle 1, on day 2 of subsequent cycles and at the end of treatment. All patients showed an initial increase in antireoviral antibody titers on day 1 of cycle 2, followed by a decrease in subsequent cycles. Conclusion: This first-in-human study demonstrated IT RC402 is well tolerated and has a manageable safety profile with preliminary clinical activity as a monotherapy and in combination with pembrolizumab. These results warrant further clinical development of RC402. Citation Format: Mark Voskoboynik, Jia Liu, Ki-Hoon Song, Dong-Guk Park, Min-Hee Ryu, Hong Jae Chon, Chan Kim. A first-in-human phase 1 dose-escalation and expansion study of intratumoral oncolytic reovirus (RC402) as a monotherapy or in combination with pembrolizumab in advanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT186.

Effect of Photobiomodulation Therapy Dosage on Orthodontic Movement, Temporomandibular Dysfunction and Third Molar Surgery Outcomes: A Five-Year Systematic Review

(1) Background: This five-year systematic review seeks to assess the impact of oral and peri-oral photobiomodulation therapies (PBMTs) on the adjunctive management of deeper tissue biofunction, pathologies related to pain and inflammatory disorders and post-surgical events. (2) Methods: The search engines PubMed, Cochrane, Scopus, ScienceDirect, Google Scholar, EMBASE and EBSCO were used with appropriate Boolean operatives. The initial number of 14,932 articles was reduced to 261. Further exclusions performed to identify PBM therapy in third molar surgery, orthodontic and TMJ articles resulted in 19, 15 and 20 of these, respectively. Each paper was scrutinised to identify visible red–NIR laser wavelength PBM applications, concerning dosimetry and outcomes. (3) Results: A dataset analysis was employed using post hoc ANOVA and linear regression strategies, both with a Bonferroni correction (p &lt; 0.05). The outcomes of articles related to oral surgery pain revealed a statistically significant relation between PBMT and a positive adjunct (p = 0.00625), whereas biofunction stimulation across all other groupings failed to establish a positive association for PBMT. (4) Conclusions: The lack of significance is suggested to be attributable to a lack of operational detail relating to laser operating parameters, together with variation in a consistent clinical technique. The adoption of a consistent parameter recording and the possible inclusion of laser data within ethical approval applications may help to address the shortcomings in the objective benefits of laser PBM.

Impact of COVID-19 on People Living With HIV: Data From Five Medical Monitoring Project Sites, 2020-2022.

The COVID-19 pandemic disrupted global economic and healthcare systems. People living with HIV (PLWH) represent a marginalized and stigmatized population who may have been particularly impacted. The purpose of this analysis was to describe the impact of the COVID-19 pandemic on PLWH in the United States. United States. We analyzed surveys of behavioral and clinical characteristics of PLWH residing in 5 states that participated in the Medical Monitoring Project between 2020 and 2022. We described the impact of COVID-19 illness, testing, and diagnoses; receipt of medical care; social service access; employment; and preventive measures by project site and demographic characteristics. Unweighted data from 1715 PLWH were analyzed. A high proportion of PLWH had medical care disrupted by the pandemic; 31% of PLWH missed medical appointments, 26% missed routine laboratory test results, and 7% missed antiretroviral therapy doses. In total, 30% of PLWH reported losing wages and 19% reported difficulty in accessing social services. Overall, 88% reported receiving at least 1 dose of COVID-19 vaccine, but vaccine uptake was low among younger, Black, and Hispanic or Latina/o/x PLWH. This descriptive analysis reinforces previous findings that show that COVID-19 negatively impacted PLWH and their ability to obtain medical care. Additional efforts will be critical to ameliorating the longer-term impacts of COVID-19 on the health of PLWH and supporting PLWH through future pandemics and healthcare system disruptions.

Study of the effect and safety of oral lactoferrin therapy for functional iron deficiency anemia in prevalent hemodialysis patients

Background The commonly available therapeutic approaches for treating anemia of chronic kidney disease include oral and IV iron supplementation and erythropoiesis-stimulating agents. Lactoferrin, an iron-binding glycoprotein, has been studied for its effect on iron homeostasis. Aim of the work To study the effect and safety of oral lactoferrin therapy for functional iron deficiency anemia in prevalent hemodialysis patients. Patients and methods This is an interventional case–control study, conducted at Ain Shams University Hospital hemodialysis unit on 70 prevalent hemodialysis patients, who were divided into two groups: (Group A): 35 patients with functional iron-deficiency anemia, who received lactoferrin together with the recommended dose of ESA therapy for 3 months, (Group B): 35 patients with functional iron-deficiency anemia, who received only their recommended dose of ESA therapy for 3 months. Results Both groups were age and sex-matched. Both groups showed a significant improvement in their hemoglobin, ferritin, and iron levels after 3 months’ follow-up, with no difference between both groups. No significant difference was noticed in either WBCs or platelets during the study period. Conclusion Oral lactoferrin failed to show a superior effect on ESAs alone and could not be used as a substitute to totally replace IV iron supplementation in hemodialysis patients with FID.

Immature platelets and platelet reactivity in patients with acute ST-segment Elevation Myocardial Infarction using whole blood flow cytometry with SYTO-13 staining

BackgroundReduced effect of antiplatelet therapy has been reported in patients with ST-segment elevation myocardial infarction (STEMI). Multiple factors may concur to explain this, including increased amount of highly reactive immature platelets. ObjectivesTo investigate the association between immature platelets and reactivity determined with multicolour flow cytometry using the SYTO-13 dye in STEMI patients. MethodsWe conducted an observational study of 59 patients with acute STEMI. Blood samples were obtained within 24 h after admission and after loading doses of dual antiplatelet therapy. For comparison, samples were obtained from 50 healthy individuals. Immature platelets and platelet reactivity were investigated using multicolour flow cytometry including the SYTO-13 dye that binds to platelet RNA and thus provides a method for subdividing platelets into immature and mature platelets. Additionally, we assessed platelet aggregation, serum-thromboxane B2 levels and standard immature platelet markers. ResultsImmature platelets were more reactive than mature platelets in both STEMI patients and healthy individuals (p-values < 0.05). STEMI patients had lower platelet aggregation and thromboxane B2 levels than healthy individuals. We found a positive association between automatically determined immature platelet markers and CD63 expression on activated platelets (Spearman's rho: 0.27 to 0.58, p-values < 0.05). ConclusionsOur study shows that immature platelets identified with a multicolour flow cytometric method using the SYTO-13 dye are more reactive than mature platelets in patients with acute STEMI and in healthy individuals. The presence of immature platelets may be important for the overall platelet reactivity, which may have implications for the effect of antiplatelet therapy.

Investigation of skin dose of post-mastectomy radiation therapy for the halcyon and tomotherapy treatment machine: Comparison of calculation and in vivo measurements

In treatments such as post-mastectomy radiation therapy (PMRT) for breast cancer patients, skin doses are of great importance in terms of tumor control and side effects. This dosimetric study aimed to measure the skin dose on the chest wall surface for post-mastectomy radiotherapy with Tomotherapy and Halcyon devices using thermoluminescence dosimetry (TLD) and to evaluate the accuracy of the skin dose calculated by treatment planning systems (TPS). Computed tomography (CT) images of the Alderson Rando phantom were obtained. Treatment plans were created with Tomotherapy and Halycon devices for a total of 50 Gy with a fraction dose of 2 Gy to the target volume. The left chest wall was divided into 9 regions for detailed surface dose assessment. 88 dose measurement points were determined on the left chest wall. The phantom was irradiated separately in Halycon and Tomotherapy devices. In vivo, dose measurements were performed with TLD in both devices. TPS and TLD doses were compared for the left chest wall surface. For skin dose, TLD measurements were lower than the dose estimate by Tomotherapy TPS and higher than the dose estimate by Halycon TPS. In addition, the skin dose measurements showed that the skin dose of the Tomotherapy device was higher than that of the Halycon. It is recommended to consider the distance of the treatment device and the accuracy of the TPS dose calculation in skin dose assessment in PMRT.

436 Immunotherapy Sensitization via Tumor Acidosis Mitigation by Esomeprazole Monitored with MRI

OBJECTIVES/GOALS: Acidity and the lactate-to-pyruvate ratio correlate with immunotherapy resistance. AcidoCEST MRI and hyperpolarized magnetic resonance spectroscopy (HP-MRS) measure extracellular pH and lactate-to-pyruvate ratio. We will establish a baseline for these biomarkers then observe changes after combination esomeprazole and immunotherapy. METHODS/STUDY POPULATION: We used multiple melanoma models created via serial in vivo passage under immunotherapeutic pressure (FVAX, CTLA-4, PD-1, PD-L1). We used four of these corresponding to 25%, 50%, 75% and 100% resistance (TMT, F2, F3, and F4, respectively). HP-MRS was performed two weeks post implantation in male BL6 mice with AcidoCEST MRI 2-3 days later. Tumors were implanted in additional mice and grown for 1 week. We used esomeprazole as a possible immunotherapy sensitizer. Esomeprazole (or PBS) alone and in combination with immune checkpoint blockade (ICB; αCTLA-4, αPD-1) was then conducted every 3 days for 3 doses. ICB was administered 3h after esomeprazole. AcidoCEST MRI was performed the day after the final dose of combination therapy and 3h after esomeprazole (or PBS) alone. HP-MRS was performed 2-3 days after acidoCEST MRI. RESULTS/ANTICIPATED RESULTS: There was a statistical increase in the lactate-to-pyruvate ratio of the F4 group compared with TMT, F2, and F3 groups (p &lt; 0.05). The TMT, F2, and F3 groups did not differ significantly. The extracellular pH (pHe) of the TMT group was statistically lower than the F2 and F4 groups (p &lt; 0.05). The pHe did not differ significantly between the TMT and F3 groups nor the F2, F3, and F4 groups. The lactate-to-pyruvate ratio and pHe after combination treatment with esomeprazole and ICB did not differ compared to PBS+ICB control. Treatment with esomeprazole alone generated higher lactate-to-pyruvate ratio compared with PBS alone. Tumor volume curves and survival curves of mice bearing F4 tumors treated with esomeprazole combination with ICB showed no difference compared with PBS+ICB, PBS alone, and esomeprazole alone. DISCUSSION/SIGNIFICANCE: We differentiated between the 100% and 25% resistant models with both pHe and lactate-to-pyruvate ratio, although the pHe was counterintuitive. Esomeprazole was ineffective, but other potential sensitizers exist. A non-invasive clinical imaging tool and sensitizer would permit more personalized treatment plans so treatment is more effective.

A Comparative Study of Clinical Outcomes in Locally Advanced Cervical Cancer: External Beam Radiotherapy (EBRT) and Sequential High Dose Rate Intracavitary Brachytherapy (HDRICBT) with or without Concurrent Cisplatin on the Day of ICBT Insertion - A Tertiary Care Center Randomized Controlled Trial in India.

The current study aimed to delve into the comparative clinical outcomes between external beam radiation therapy (EBRT) and sequential High Dose Rate Intracavitary Brachytherapy (HDRICBT) with or without concurrent cisplatin administration on the day of intracavitary brachytherapy (ICBT) insertion in women with locally advanced cervical cancer. In this study, conducted between January 2017 and July 2018 at a leading institute in India, diagnosed and untreated patients of locally advanced carcinoma cervix were randomized into two groups. Arm 1 received concurrent cisplatin before each course of brachytherapy, while Arm 2 underwent brachytherapy alone. The outcomes were compared in terms of acute and late toxicities, treatment response, and follow-up. Data analysis was performed using SPSS 16, with statistical significance set at p < 0.05. Both study arms showed similar complete response (CR) rates of 73.3%, with no significant advantage of concurrent cisplatin before brachytherapy. However, a noteworthy trend emerged during follow-up. In the concurrent cisplatin group, the CR rate increased from 73.3% post 1 month of brachytherapy to 86.7% at 3 months and 83.3% at 6 months. Contrastingly, the control group showed CR rates of 73.3% post 1 month, 80% at 3 months, and 76.6% at 6 months. While not statistically significant, this observation suggests a possible enhancement in response rates with concurrent cisplatin and ICBT. Future studies focusing on the optimal drug, dosage, scheduling, and combining cisplatin with other agents are recommended to further explore the potential benefits observed in this study.

Inhaled nitric oxide and postoperative outcomes in cardiac surgery with cardiopulmonary bypass: A systematic review and meta-analysis

Cardiac surgeries under cardiopulmonary bypass (CPB) are complex procedures with high incidence of complications, morbidity and mortality. The inhaled nitric oxide (iNO) has been frequently used as an important composite of perioperative management during cardiac surgery under CPB. We conducted a meta-analysis of published randomized clinical trials (RCTs) to assess the effects of iNO on reducing postoperative complications, including the duration of postoperative mechanical ventilation, length of intensive care unit (ICU) stay, length of hospital stay, mortality, hemodynamic improvement (the composite right ventricular failure, low cardiac output syndrome, pulmonary arterial pressure, and vasoactive inotropic score) and myocardial injury biomarker (postoperative troponin I levels). Subgroup analyses were performed to assess the effect of modification and interaction. These included iNO dosage, the timing and duration of iNO therapy, different populations (children and adults), and comparators (other vasodilators and placebo or standard care). A comprehensive search for iNO and cardiac surgery was performed on online databases. Twenty-seven studies were included after removing the duplicates and irrelevant articles. The results suggested that iNO could reduce the duration of mechanical ventilation, but had no significance in the ICU stay, hospital stay, and mortality. This may be attributed to the small sample size of the most included studies and heterogeneity in timing, dosage and duration of iNO administration. Well-designed, large-scale, multicenter clinical trials are needed to further explore the effect of iNO in improving postoperative prognosis in cardiovascular surgical patients.

Effects of Manual Therapy Plus Pain Neuroscience Education with Integrated Motivational Interviewing in Individuals with Chronic Non-Specific Low Back Pain: A Randomized Clinical Trial Study.

Background and Objectives: Chronic non-specific low back pain (CNLBP) persists beyond 12 weeks. Manual therapy recommended for CNLBP demonstrates short-term efficacy. Pain Neuroscience Education (PNE) teaches patients to modify pain perception through explanations, metaphors, and examples, targeting brain re-education. Motivational Interviewing (MI) enhances motivation for behavioral change, steering patients away from ambivalence and uncertainty. These approaches collectively address the multifaceted nature of CNLBP for effective management. The aim of this study was to investigate a manual therapy intervention combined with PNE with MI on pain, pressure pain threshold (PPT), disability, kinesiophobia, catastrophizing, and low back functional ability in individuals experiencing CNLBP. Materials and Methods: Sixty adults with CNLBP were randomly divided into three equal groups (each n = 20). The first group received manual therapy and PNE with integrated MI (combined therapy group), the second group underwent only manual therapy (manual therapy group), and the third group followed a general exercise program at home (control group). Pain in the last 24 h was assessed using the Numeric Pain Rating Scale (NPRS), functional ability with the Roland-Morris Disability Questionnaire (RMDQ), PPT in the lumbar region through pressure algometry, kinesiophobia with the Tampa Scale for Kinesiophobia (TSK), catastrophizing with the Pain Catastrophizing Scale (PCS), and performance using the Back Performance Scale (BPS) at baseline, in the fourth week, and six months post-intervention. Results: Statistically significant differences between the intervention groups and the control group were found in both the fourth-week measurement and the six-month follow-up, as evident in the NPRS and RMDQ scores, as well as in the total values of tested PPTs (p < 0.05). Differences were also observed between the two intervention groups, with a statistically greater improvement in the combined therapy group at both time points (fourth week and six-month follow-up) (p < 0.05). Regarding the TSK and PCS scores in the fourth week, statistically significant differences were observed between the two intervention groups compared to the control group, as well as between the two intervention groups (p < 0.05). However, in the six-month follow-up, statistically significant differences were found only between the combined therapy group and the other two groups, with the combined therapy group showing significant improvements (p < 0.05). In relation to BPS, both intervention groups exhibited statistically significant differences compared to the control group in the fourth week, without any significant differences between the two intervention groups. However, in the six-month follow-up, significant differences were noted between the combined therapy group and the other two groups (p < 0.05), with combined therapy demonstrating greater improvement. Conclusions: The addition of PNE with integrated MI enhanced the positive effects of a manual therapy intervention in all outcome measures. The combination of manual therapy plus PNE with integrated MI appeared to provide greater improvements compared to the isolated application of manual therapy, and these improvements also lasted longer. These short- and long-term positive effects are likely attributed to the combination of PNE with integrated MI, which contributed to increasing the effectiveness of the treatment. Further studies are required to investigate the optimum dosage of manual therapy and PNE with integrated MI in individuals with CNLBP.

Appropriate thromboprophylaxis strategy for COVID-19 patients on dosage, antiplatelet therapy, outpatient, and postdischarge prophylaxis: a meta-analysis of randomized controlled trials.

There was controversy surrounding the optimal thromboprophylaxis strategy for coronavirus disease 2019 (COVID-19) patients. This included debates on the dosage of anticoagulants for thromboembolism prophylaxis, the requirement for additional antiplatelet therapy, and the necessity of prophylaxis for outpatients and postdischarge. To explore this, the authors performed a meta-analysis of randomized controlled trials. PubMed, Cochrane Library, Embase, and Web of Science were last searched on 26 July 2023 for studies comparing the effect of different dose of anticoagulation, additional antiplatelet, and postdischarge prophylaxis for COVID-19 patients. The results of eligible studies were analyzed in terms of thromboembolism events, major bleeding and all-cause mortality during follow-up. Our study included a total of 25 randomized controlled trials, involving 17911 patients. Our results revealed that, compared to prophylactic dose, therapeutic dose showed lower thrombotic risk (RR, 0.66; 95% CI: 0.45-0.96) but had similar major bleeding risk for critically ill patients with COVID-19. On the other hand, intermediate dose and prophylactic dose demonstrated similar thromboembolism risk and major bleeding risk. For noncritically ill patients with COVID-19, therapeutic dose of anticoagulants was associated with lower thrombotic risk (RR, 0.50; 95% CI: 0.34-0.72) but, at the same time, increased the risk of major bleeding (RR, 2.01; 95% CI: 1.22-3.33). However, intermediate dose showed lower thromboembolism risk (RR, 0.38; 95% CI: 0.21-0.69) while maintaining a similar major bleeding risk. In critically ill patients, additional antiplatelet therapy showed similar thromboembolism, major bleeding risk, and mortality when compared to no treatment. For outpatients, additional prophylactic anticoagulation showed similar thromboembolism, major bleeding risk, and mortality when compared to no treatment. For postdischarge patients, postdischarge prophylaxis reduced thromboembolism risk (RR, 0.49; 95% CI: 0.31-0.76) but increased major bleeding risk (RR, 2.63; 95% CI: 1.13-6.14). For noncritically ill patients, therapeutic dose prophylactic anticoagulation significantly reduced venous thromboembolism but increases major bleeding risk. Intermediate dose effectively lowered venous thromboembolism without raising major bleeding risk. The optimal dose and need for additional antiplatelet therapy in critically ill patients, as well as the necessity of prophylactic anticoagulation in outpatient and postdischarge patients, required further investigation and confirmation through rigorous evidence studies.

Dysphagia therapy in adults with a tracheostomy: A scoping review protocol.

Swallowing impairment (dysphagia) and tracheostomy coexist. Research in this area has often provided an overview of dysphagia management as a whole, but there is limited information pertaining to specific dysphagia therapy in the tracheostomy population. The aim of this scoping review is to provide a detailed exploration of the literature with regard to dysphagia therapeutic interventions in adults with a tracheostomy. The scoping review will describe current evidence and thus facilitate future discussions to guide clinical practice. A scoping review using the Joanna Briggs Institute and Preferred Reporting Items for Systematic Reviews guideline will be used. Ten electronic databases from inception to December 2023 and grey literature will be searched. From identified texts forward and backward citation chasing will be completed. Data extraction will compose of population demographics, aetiology and dysphagia therapy (type, design, dose and intensity). A number of citations and papers included in the scoping review will be presented visually. The scoping review aims to expand upon the existing literature in this field. A detailed description of the evidence is required to facilitate clinical discussions and develop therapeutic protocols in a tracheostomised population. The results of this scoping review will support future research in dysphagia therapy and provide the basis for the development of best practice guidelines. What is already known on this subject There is an abundance of evidence available regarding dysphagia therapy targeting impairments of the swallowing sequence in a variety of populations including stroke, head and neck cancer, progressive neurological conditions and critical illness. However, there is a paucity in the literature with regard to identifying dysphagia therapy for adults with a tracheostomy. What this study adds The study protocol aims to describe the methodological features that need to be extracted from existing studies to outline dysphagia therapy for adults with a tracheostomy. To the researchers' knowledge, this is the first study protocol to describe the methodological features of dysphagia therapy for people with a tracheostomy from the literature using a standardised approach (Joanna Briggs Institute and Preferred Reporting Items for Systematic Reviews and Meta-Analyses [PRISMA] guideline). This will ensure that the protocol is replicable for other researchers to use and demonstrates transparency in research methods. What are the clinical implications of this work? The development of a robust protocol is necessary in order to facilitate the scoping review to describe the current evidence and thus facilitate future discussions to guide clinical practice for speech and language therapists working with adults who have a tracheostomy and dysphagia. The publication of the scoping review protocol allows future clinical researchers in the area of tracheostomy and dysphagia management a blueprint with which to narrow their own research questions and it also enables replicability as the principles of good research practice dictate.

Abstract 6382: Risk prediction of dyslipidemia in long-term survivors of childhood cancer: A report from the St. Jude Lifetime Cohort

Abstract Background: Dyslipidemia is a significant contributor to the increased risk of cardiovascular morbidity and premature mortality in long-term survivors of childhood cancer. Identifying individuals at risk at an early stage provides an opportunity for tailored prevention approaches. Methods: Long-term childhood cancer survivors from the St. Jude Lifetime Cohort, (SJLIFE, n=2,559; median age 41 years, range 20-77 years) were directly assessed for dyslipidemia. Risk factors under consideration included demographic characteristics, cancer treatment exposures (cumulative doses of anthracyclines, platinum agents, glucocorticoids, and radiation therapy), comorbid conditions at the time of assessment (hypertension, diabetes mellitus, growth hormone deficiency, hypogonadism, hypothyroidism, cardiomyopathy, and chronic kidney disease), and externally validated multi-ancestry general-population polygenic risk scores (PRSs) for lipid values (total cholesterol, LDL-C, HDL-C, and triglycerides). Multivariable logistic regression predicted a 15-year risk of dyslipidemia (CTCAE grade ≥2 hypercholesterolemia and/or hypertriglyceridemia) including variables selected by the stepwise approach. Performance of the model was assessed by the area under the receiver operating characteristic curve (AUC). Results: Dyslipidemia was clinically identified in 543 (25.1%) SJLIFE survivors. AUC of a clinical model with sex, race, age at prediction, and comorbid conditions (diabetes, growth hormone deficiency, hypogonadism, hypothyroidism, and hypertension) was 0.80 (95% CI, 0.78-0.82). Inclusion of cancer treatment exposures (cumulative doses of anthracyclines, cisplatin, carboplatin, glucocorticoids, abdominal and cranial radiation therapy) significantly increased AUC to 0.82 (95% CI, 0.80-0.84; P=2.1×10-4). Addition of two PRSs for LDL-C (one included only genome-wide significant variants adjusted for statins and another consisted of all genome-wide variants) and the PRS for triglycerides provided further significant improvement in AUC to 0.86 (95% CI, 0.84-0.88; P=4.2×10-12). Conclusions: We developed a prediction model with good performance for identifying the risk of dyslipidemia in childhood cancer survivors. In addition to demographics and comorbidities, cancer treatments and inherited genetic factors contributed significantly to improving the risk prediction of dyslipidemia. Results may refine risk stratification for dyslipidemia in survivors and present opportunities for more precise and personalized preventive strategies to address cardiovascular health. Independent validation in survivors from the Childhood Cancer Survivor Study and the Dutch Childhood Cancer Survivor Study (DCCSS)-LATER is currently underway. Citation Format: Kateryna Petrykey, Kendrick Li, Lu Xie, Achal Neupane, Angela Delaney, Christine Yu, Stephanie B. Dixon, Bonnie Ky, Cindy Im, Isaac B. Rhea, Jeffrey A. Towbin, Jason N. Johnson, Melissa Bolier, Vincent G. Pluimakers, Linda Broer, Sebastian J. Neggers, Marry M. van den Heuvel-Eibrink, Rebecca M. Howell, Kirsten K. Ness, Melissa M. Hudson, Gregory T. Armstrong, Yutaka Yasui, Yadav Sapkota. Risk prediction of dyslipidemia in long-term survivors of childhood cancer: A report from the St. Jude Lifetime Cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6382.