Treatment Modalities Research Articles

Clinical Investigation of Short-Term Axial Elongation Control After Orthokeratology Lens Correction: Exploring Its Predictive Role in Long-Term Therapeutic Efficacy

Objective: This study was developed with the goal of exploring the efficacy of orthokeratology (OK) as an approach to controlling axial length (AL) growth and identifying factors predictive of the long-term efficacy of this approach. Methods: This was a retrospective study that enrolled 157 myopic children 7 to 15 years of age undergoing OK correction for over 3 years. The short- and long-term effectiveness of this approach at 1 and 3 years post-OK correction, respectively, was assessed. All participants were classified into two groups based on whether they exhibited good or poor long-term efficacy outcomes. Measurements of changes in AL were made at baseline and at 1 and 3 years post-OK. Univariate analyses and binary logistic regression approaches were used to evaluate baseline age, baseline spherical equivalent refraction, baseline keratometry (K) values of flat and steep meridians, and short-term effectiveness with the goal of identifying predictors of long-term efficacy. Results: Univariate analyses led to the identification of significant differences in baseline age, baseline spherical equivalent refraction, baseline AL, and short-term efficacy between these two groups (P<0.05), whereas gender, baseline flat K, and baseline steep K did not differ significantly (P>0.05). In binary logistic regression analyses, baseline AL (P=0.017) and short-term efficacy (P<0.001) were both found to significantly influence long-term efficacy. Receiver operating characteristic curves demonstrated that short-term efficacy offered an area under the curve value >0.8, consistent with its highly accurate performance as a predictor of long-term efficacy. Conclusion: These results suggest that short-term efficacy outcomes can feasibly be used to predict the long-term effectiveness of OK correction in children. In patients exhibiting poor short-term efficacy, timely replacement or the incorporation of additional treatment modalities may aid efforts to better control the progression of myopia.

Contemporary Approaches to Wound Burn Healing

The World Health Organization (WHO) reports that over 11 million individuals get burns annually, resulting in 180,000 fatalities. A burn is a condition resulting by heat, chemical agents, electrical currents, or other forces that inflict tissue damage. Burns primarily impact the skin, however they may also include deeper structures, including bones and muscles. Upon combustion, the skin forfeits its primary functions, including protection against the external environment, infections, moisture evaporation, and thermal regulation. Based on the burn's stage, the patient's health, and the burn's etiology, it is essential to choose the most suitable therapy. Personalization and interdisciplinary teamwork are essential for the effective therapy of burn victims. This thorough study compiles and examines the existing treatment modalities, emphasizing current advancements in topical therapies, wound debridement, dressings, skin grafting, nutritional support, pain management, and scar tissue therapy.

Supracostal ultrasound guided approach percutaneous nephrolithotomy (SUGA-PNL) versus retrograde intrarenal surgery for large volume isolated upper calyceal stones: a prospective randomized analysis

To assess outcomes of supracostal ultrasound guided approach percutaneous nephrolithotomy (SUGA-PNL) and retrograde intrarenal surgery (RIRS) in isolated large volume upper calyceal stones (UCS). This was a prospective randomized study including patients with isolated UCS > 20mm. The patients were randomized into two groups: group (P) (SUGA-PNL) and group (R) (RIRS). Patients’ demographics, stones characteristics, operative, and postoperative outcomes essentially the stone free rate (SFR) and complications rate were documented. The stone clearance was defined as no fragments or residual fragments less than 2mm in the one month non contrast CT scan follow up. Eighty-nine patients opted to undergo the procedure according to the preoperative randomization. Four patients, 2 patients from each group, lost to follow up and other 2 patients were excluded from group (R) due to a tight ureter. Both groups were comparable as regards the preoperative demographics and stone characteristics. There were statistically significant differences regarding total operative time, the change in hemoglobin level, and postoperative pain score (P: 0.024, 0.010 and 0.032 respectively). The SFR was 88.1% in group (P) compared to 73.2% in group (R) (P: 0.019). Moreover, it did not differ significantly between both groups regarding the intraoperative and postoperative complications. No visceral and thoracic injuries were documented in group (P). On other side, 6 patients (14.6%) from group (R) had different grades of ureteral injury during access sheath placement. SUGA-PNL is a safe and effective treatment modality for UCS > 20mm with a higher SFR than RIRS.

Chronic Hepatitis D Virus Infection and Its Treatment: A Narrative Review

More than 12 million individuals worldwide are chronically infected with the hepatitis D virus (HDV). HDV infection is the most severe form of viral hepatitis since it requires hepatitis B virus co-infection and accelerates progression to cirrhosis and hepatocellular carcinoma. Therefore, treatment modalities to slow the progression of the disease are essential but not yet available. In addition, no antiviral treatment to date has been shown to reliably eradicate HDV. Pegylated interferon (PEG-IFN) is the only universally used treatment to suppress HDV RNA replication and improve liver inflammation and fibrosis. This treatment can be completed in 12–18 months, but cure rates remain low, and success does not reliably increase with the addition of a nucleos(t)ide analog. PEG-IFN therapy is also limited by poor tolerability and multiple adverse effects, including neutropenia, thrombocytopenia, and neuropsychiatric symptoms. Newer antiviral therapies in development target unique aspects of HDV viral replication and show promising results in combination with PEG-IFN for long-term HDV RNA suppression. These newer antiviral therapies include buleviritide (which blocks HDV entry), lonafarnib (which prevents HDV assembly), and REP-2139 (which prevents HDV export). In this manuscript, we discuss the characteristics of HDV infection and review the new antiviral therapies approved for treatment and those under investigation.

Primary hepatoid adenocarcinoma of the lung in patient with silicosis: a case report and literature review

IntroductionHepatoid adenocarcinoma of the lung (HAL) is a special type of adenocarcinoma originating from the lung with adenoid- and hepatocyte-like differentiation. HAL is rare in clinical practice. Here, we present the case of a patient with HAL.Case presentationA 59-year-old man was admitted to the hospital 4 days because of lung mas observed. Chest computed tomography (CT) revealed a lobulated mass shadow in the right lower lobe, approximately 3.5 × 3.3 cm in size. CT-guided percutaneous biopsy of the right lower lung was performed. The pathological results indicated a moderately to poorly differentiated adenocarcinoma. The patient underwent thoracoscopic right middle and lower lobectomy and systematic lymph node dissection. The postoperative pathology was primary HAL, with the staging of T2bN2M0 (stage III A). Recurrence-free survival and overall survival were 6 and 19 months, respectively Preoperatively, the level of alpha-fetoprotein was negative; however, after recurrence, it increased to 87.8.ConclusionPulmonary hepatoid adenocarcinoma is a rare subtype of malignant lung tumor, combined silicosis is more rare. Early surgical intervention can benefit patients in the early stages of the disease, whereas chemotherapy remains the main systemic treatment modality for postoperative and advanced stages. With the increasing popularity of genetic testing, it is important to focus on improving genetic examination.

Targeting a chemo-induced adaptive signaling circuit confers therapeutic vulnerabilities in pancreatic cancer

Advanced pancreatic ductal adenocarcinomas (PDACs) respond poorly to all therapies, including the first-line treatment, chemotherapy, the latest immunotherapies, and KRAS-targeting therapies. Despite an enormous effort to improve therapeutic efficacy in late-stage PDAC patients, effective treatment modalities remain an unmet medical challenge. To change the status quo, we explored the key signaling networks underlying the universally poor response of PDAC to therapy. Here, we report a previously unknown chemo-induced symbiotic signaling circuit that adaptively confers chemoresistance in patients and mice with advanced PDAC. By integrating single-cell transcriptomic data from PDAC mouse models and clinical pathological information from PDAC patients, we identified Yap1 in cancer cells and Cox2 in stromal fibroblasts as two key nodes in this signaling circuit. Co-targeting Yap1 in cancer cells and Cox2 in stroma sensitized PDAC to Gemcitabine treatment and dramatically prolonged survival of mice bearing late-stage PDAC, whereas simultaneously inhibiting Yap1 and Cox2 only in cancer cells was ineffective. Mechanistically, chemotherapy triggers non-canonical Yap1 activation by nemo-like kinase in 14-3-3ζ-overexpressing PDAC cells and increases secretion of CXCL2/5, which bind to CXCR2 on fibroblasts to induce Cox2 and PGE2 expression, which reciprocally facilitate PDAC cell survival. Finally, analyses of PDAC patient data revealed that patients who received Statins, which inhibit Yap1 signaling, and Cox2 inhibitors (including Aspirin) while receiving Gemcitabine displayed markedly prolonged survival compared to others. The robust anti-tumor efficacy of Statins and Aspirin, which co-target the chemo-induced adaptive circuit in the tumor cells and stroma, signifies a unique therapeutic strategy for PDAC.

Clinical efficacy of intracavernous injection of platelet lysate for erectile dysfunction

BackgroundAmong the emerging treatments for erectile dysfunction (ED), platelet-rich plasma (PRP), known for its ability to enhance tissue repair and regeneration, stands out as a promising therapeutic approach. In this innovative study, we aimed to assess the efficacy of intracavernous injections of platelet lysate (PL), a derivative of PRP, in improving erectile function among ED patients.MethodsWe enrolled twenty-six patients, aged between 35 and 70 years (mean age 51.6 ± 11.3 years), who had been experiencing ED for over six months and had an International Index of Erectile Function-5 (IIEF-5) score of 21 or less. Participants received autologous PL injections intracavernously every two weeks for a total of five administrations. We assessed Erection Hardness Score (EHS) and International Index of Erectile Function-5 (IIEF-5) bi-weekly for 16 weeks and conducted penile Doppler ultrasounds pre- and post-treatment to record peak systolic velocity (PSV) and resistance index (RI).ResultsBefore treatment, the mean EHS was 2.15 ± 0.88 and IIEF-5 was 10.92 ± 5.28. Remarkable improvements were observed post-treatment, with the EHS significantly increasing to 3.15 ± 0.83 (p < 0.05) and IIEF-5 to 17.23 ± 5.26 (p < 0.05). Penile Doppler ultrasound exhibited an increase in both PSV and RI post-treatment, with the rise in RI being statistically significant.ConclusionsOur findings indicate that intracavernous injections of PL substantially enhance erectile function, as evidenced by improvements in EHS, IIEF-5, and the RI of penile Doppler ultrasound, without hemorrhagic events or other adverse reactions apart from temporary pain at the injection site during the 16-week follow-up period. These encouraging results suggest that PL injections are a safe and effective treatment modality for patients with moderate ED, potentially providing a less invasive and more physiologically friendly alternative to current ED management strategies.Trial registrationThe study received approval from the Institutional Review Board of National Taiwan University Hospital (IRB Number 202008061RIPC, date of registration 08/28/2020).

Lasers efficacy in pain management after primary and secondary endodontic treatment: a systematic review and meta-analysis of randomized clinical trials

Postoperative pain is a common concern following root canal treatments (RCT), impacting both patients and oral health practitioners. This systematic review and meta-analysis aimed to evaluate the effectiveness of laser treatment modalities in reducing postoperative pain compared to conventional methods after primary and secondary RCT in permanent mature teeth. A search of three electronic databases (PubMed, ScienceDirect, and The Cochrane Library) was conducted, using a broad range of keywords and terms. Gray literature and manual searches were conducted to complement the search. The inclusion criteria included randomized clinical trials based on the objective of the secondary study. A minimum sample size of 10 participants per group and a clearly defined criterion for postoperative pain assessment were required. The characteristics of the included studies were presented as tables. The Cochrane collaboration tool RoB 2.0 was used to assess the risk of bias within each study. Two reviewers extracted the data and assessed the studies independently, and discrepancies were resolved through consultation with a third reviewer. A random-effects model was employed for meta-analysis to estimate the overall effect measure. Heterogeneity was evaluated using Cochran’s Q test and the I2 index. Publication bias was explored via Funnel plots and Egger’s test. Subgroup analyses and meta-regression were conducted to assess variations among laser methods and examine the influence of independent factors. The significance threshold for all analyses was set at 5% (α = 0.05). Intraoral laser therapy demonstrated no significant advantage over conventional treatments but consistently outperformed placebo, particularly from 4 to 72 h post-treatment. Low-level laser therapy provided slight pain reduction in the first 8 h, though its effectiveness diminished in retreatment scenarios. Photodynamic therapy and laser disinfection showed marginal benefits, especially shortly after treatment, with reduced efficacy in longer-term or retreatment contexts. Further research is needed to explore different applications of laser modalities and assess distinct prognostic factors in more detail.

Acute myocarditis presentation and intra-hospital prognosis: results of the multicenter prospective MYOCARDITIRM study

Abstract Background Acute myocarditis (AM) usually presents as chest pain with rising troponin and normal coronary arteries. Despite frequent favorable evolution at the acute phase, it is associated with heart failure and ventricular rhythm disorders and is considered the leading cause of sudden cardiac death in young apparently healthy adults. There is no recommendation for AM, only expert consensus, given the lack of important databases for a strong level of confidence. Methods We performed a multicenter prospective observational study of patients admitted for AM acknowledged by cardiac MRI to describe baseline characteristics, management, in-hospital and long-term outcomes of AM patients in France. Secondary objectives were to investigate determinants of prognosis, modalities of treatment and follow-up, and to identify gaps between expert consensus and real-life management. Results We enrolled 805 consecutive patients hospitalized for AM in 49 participating centers between May 2016 and February 2019. Median age was 31 (IQR 23-41) with 19% of female. Chest pain was the most frequent symptom (93%) and 112 (14%) had severity criteria upon admission (LVEF&amp;lt;50% or severe ventricular arrythmia or high-grade AV block or cardiogenic shock). ST elevation was observed in 49% of patients. One 26-years old patient died during initial hospital stay. Overall, 62 patients (8%) experienced intra-hospital complication of their AM, defined as a combined endpoint of death, LVEF&amp;lt;40% (MRI), sustained ventricular or supraventricular arrythmia, acute renal failure, cardiogenic shock, need for ventricular assistance device, need for inotropic drugs, temporary cardiac pacing, pace-maker or cardiac defibrillator implantation. Patients with initial severity criteria were 10 times more likely to present intra-hospital complication (33% vs 3.6%, p&amp;lt;0.001). Conclusion This prospective cohort represents the largest database on AM worldwide. Here we report baseline characteristics and in hospital events. Most patients had typical presentation with favorable outcomes but as much as 8% of patients did exhibit intra-hospital complication. The prospective follow up will provide valuable data to better identify subset of patients with poor prognosis that may be of interest to develop new therapeutic strategies.Acute myocarditis on cardiac MRI

The impact of peptide receptor radionucleotide therapy with Lutetium-177 DOTATATE on cardiac metastases in neuroendocrine tumors

Abstract Background Cardiac metastasis from neuroendocrine tumors (NET) is rare and has been thought to potentially result in life threatening sequalae. Peptide receptor radionucleotide therapy (PRRT), such as Lutetium-177 (Lu-177) DOTATATE, has been validated as effective treatment for patients with NET who have progressed on somatostatin analogue (SSA) therapy and more recently suggested for use in SAA-naïve higher risk grade 2 and grade 3 NETs. However, Lu-177 DOTATATE therapy has been found to have potentially serious adverse effects both locally and systemically. Overall, the clinical significance of cardiac metastasis of NET, as well as the safety and efficacy of Lu-177 DOTATATE in this cohort, has not been thoroughly evaluated. Purpose This study assessed the outcomes and clinical consequences of cardiac metastatic involvement in patients with NET. Furthermore, this study investigated the safety of Lu-177 DOTATATE therapy in patients with cardiac metastases from NET. Methods All patients who underwent 68Ga-DOTATATE positron emission tomography for evaluation of NET across three tertiary centers between 2016 and 2022 were retrospectively evaluated. Patients with evidence of cardiac metastasis were further evaluated. Baseline characteristics, treatment modality, and clinical outcomes including mortality, arrhythmia or conduction disease, carcinoid heart disease, and heart failure admissions were recorded. Patients with cardiac metastases were grouped and compared based on therapeutic modality (conservative therapy with surveillance or SSA, Lu-177 DOTATATE therapy, or surgical resection of metastases). Results From 3253 patients with NET, 51 patients were identified to have cardiac metastases (mean age 66.7 ± 12.2 years, 54% male). Three patients underwent surgical resection of cardiac metastases, and in two of whom this was concomitant while undergoing valve surgery for carcinoid heart disease. Patients with cardiac metastasis had significantly higher mortality than patients without cardiac metastasis (HR 2.12, 95%CI 1.00 – 4.52, p = 0.049, Figure 1A). Median follow-up from diagnosis of cardiac metastasis was 3.64 years [IQR 1.59 – 5.64]. There was no significant difference in clinical outcomes between patients that received Lu-177 DOTATATE therapy (n = 27) and conservative therapy (n = 21). Specifically, there was no significant difference in mortality risk at five years post the diagnosis of cardiac metastasis between these groups (p = 0.47, Figure 1B). Conclusion Patients with cardiac metastasis from NETs have worse clinical outcomes than NET patients without cardiac metastatic involvement. Lu-177 DOTATATE therapy appears to be safe in patients with cardiac metastasis from NET.Figure 1AFigure 1B

Divergent hemometabolic dynamics: understanding the differences between acute myocardial infarction and heart failure related cardiogenic shock

Abstract Background Understanding the hemodynamic trajectories between acute myocardial infarction(AMI) &amp; non-AMI cardiogenic shock(CS) is crucial for tailored management. Purpose Describe different hemometabolic patterns in AMI vs AMI-CS, AMI vs AMI-CS survivors &amp; AMI vs AMI-CS non-survivors. Methods 354 AMI &amp; 81 Non-AMI CS patients with PAC-hemodynamics were included. ANOVA of repeated measures was used to compare trajectories. Cox regression analysis for hazard ratios of conventional cut-off values hemometabolic goals &amp; ideal with Youden index for LVSWi at baseline &amp; 24h(Fig2B/C). Results AMI-CS were older(62 vs 52,P&amp;lt;0.001), exhibit a higher prevalence of smoking, dyslipidemia, HTN, &amp; DM2(P&amp;lt;0.05). HF history &amp; AF were more prevalent in Non-AMI-CS(P&amp;lt;0.001). AMI-CS had lower heart rate, respiratory rate, BUN, pH; higher LVEF, hemoglobin, leucocytes, platelets, glucose, Cl-, Na+, AST, ALT, LDH(P&amp;lt;0.05). Treatment modalities, AMI-CS had higher mechanical circulatory support (P&amp;lt;0.001). AKI was more common in non-AMI(P=0.004). There were no differences in number of vasoactives(P=0.46), but non-AMI had more dobutamine use(P&amp;lt;0.001). MODS score, organ failures, VT/VF, Phenotype, SCAI, and mortality(46.9 vs 47.7% Non-AMI vs AMI-CS) had no differences(P&amp;gt;0.05). Dynamics congestion associated with phenotypes &amp; SCAI are shown in Fig 2A. SBP(F=12.39,P&amp;lt;0.001), DBP(4.72,0.03) &amp; MAP(9.98,0.002) (Fig1A) had differences in AMI vs non-AMI-CS, but none were seen in survivors(P&amp;gt;0.05), only in non-survivors (SBP 17.52, &amp;lt;0.001; DBP 6.59, 0.011 &amp; MAP 13.98, &amp;lt;0.001). RAP(7.4,0.007) &amp; PCWP(53.51,&amp;lt;0.001) (Fig1B/C) also differ among AMI vs non-AMI &amp; non-survivors(5.69,0.018 &amp; 28.77,&amp;lt;0.001); but only PCWP differs across survivors(27.49,&amp;lt;0.001). Cardiac output &amp; index(Fig1D)(13.65,&amp;lt;0.001 &amp; 18.88,&amp;lt;0.001) had both differences among survivors(4.17,0.042 &amp; 6.67,0.01) &amp; non-survivors(10.98,&amp;lt;0.001 &amp; 13.57,&amp;lt;0.001). Cardiac power, index, &amp; CPIRAP(Fig1E) also had this behavior being higher in AMI. Coronary perfusion pressure (Fig1F) differs among all 3 classes (P&amp;lt;0.001), AMI vs non-AMI(F=31.17), survivors(11.63) &amp; non-survivors(25.81). Perfusion pressure only had in AMI vs non-AMI(15.91,&amp;lt;0.001) &amp; non-survivors(20.39,&amp;lt;0.001). PAPI(Fig1G) had differences in AMI vs non-AMI(F=9.3,P=0.002) &amp; non-survivors(8.69,&amp;lt;0.001). API(Fig1H) differs across all spectrums(14.87 groups, 5.89 survivors &amp; 11.61 non-survivors). Finally, LVSWi &amp; RVSWi(Fig1I/J) had differences among AMI vs non-AMI in all categories: groups(22.5 &amp; 14.27 both &amp;lt;0.001), survivors(7.88,0.005 &amp; 9.29,0.003) &amp; non-survivors(21.27,&amp;lt;0.001 &amp; 5.17, 0.024). In the metabolic, only lactate(Fig1K) shows differences in AMI vs non-AMI(5.46,0.02) &amp; non-survivors(8.02,0.005); no differences were noted in survivors. Hazard ratios were assessed with the whole cohort, AMI, &amp; non-AMI; full data is shown in Fig 2B/C. Conclusion Our investigation elucidates nuanced hemodynamic disparities between AMI vs non AMI-CS, even in survivors and non-survivors of CS.Figure 1.Hemodynamic trajectoriesFigure 2.Alluvial. B/C Baseline &amp; 24h goals

Development of the compliance with mechanical ventilator scale in: A validity and reliability study.

Mechanical ventilation is a widely used treatment modality in cardiac surgery intensive care units (ICUs), especially for patients requiring respiratory support during postoperative management. The aim of this study was to define the process of developing a scale to assess adherence to mechanical ventilation in cardiac surgery patients and to assess the validity and reliability of the scale. This is a scale development and scale validation study. The study was conducted with 222 patients between April and September 2023. In the first stage, face-to-face interviews were conducted with seven nurses. Based on the literature review and content analysis of the interviews, the researchers created an item pool. In the second stage, the validity and reliability of the Mechanical Ventilator Compliance Scale in cardiac surgery patients were assessed. The scale was developed to be used by nurses working in cardiac surgery ICUs. The first 36-item scale was subjected to content validity assessment by 14 experts. It was revised according to the experts' feedback and a content validity criterion of 0.83 was obtained. Confirmatory factor analysis showed good fit values for the scale (χ2/SD = 3.09, GFI = 0.90, AGFI = 0.90, CFI = 0.91, RMSEA = 0.06, and RMR = 0.07). Test-retest analysis to assess the reliability of the scale showed good agreement between responses over time (ICC: 0.932; p < .001). Cronbach's alpha values for the scale and its subscales, behavioural and physical responses were 0.956, 0.949 and 0.912, respectively. The study findings indicate that the scale is a reliable and valid tool for assessing mechanical ventilator compliance in cardiac surgery patients. This study provides nurses in cardiac surgery intensive care units with a measurement tool to objectively assess patients' compliance with mechanical ventilation therapy. The scale provides more reliable results by preventing subjective judgement and estimation in patient assessment.

Cardiovascular Mortality Risk among Patients with Liver Cancer: A SEER Database Study.

Data sourced from the Surveillance, Epidemiology, and End Results (SEER) database encompassing liver cancer diagnoses from 2000 to 2017 were utilized. The standardized mortality rate (SMR) was computed using general population reference data, and multivariate competing risk models were employed for analysis. Analysis of 70,733 liver cancer patient records revealed 1,954 instances of CVM. The overall CVM SMR for liver cancer patients was 12.01 (95% CI: 11.48-12.55). Various demographic and clinical factors, including sex, race, age, year of diagnosis, pathological type, general stage, treatment modalities, and matrimonial status, emerged as liver cancer pa-tients` independent predictors of CVM. Liver cancer patients have a notably heightened susceptibility to cardiovascular mortality (CVM) in contrast to the general populace. It is imperative to promptly recognize high-risk subcategories and execute tailored cardiovascular interventions as crucial measures to bolster survival rates within this cohort of patients.

Prognostic Evaluation of Conversion Therapy Following Hepatic Arterial Infusion Chemotherapy or Immunotherapy in Patients with Advanced or Transarterial Chemoembolization Unsuitable Intermediate-Stage Hepatocellular Carcinoma-A retrospective cohort study.

Patients with advanced-stage or intermediate-stage hepatocellular carcinoma (HCC) unsuitable for transarterial chemoembolization (TACE) had poor prognoses. Recent advancements in hepatic arterial infusion chemotherapy (HAIC) and immune checkpoint inhibitors (ICIs) have demonstrated higher tumor response rates, which improved overall survival (OS). HAIC achieves an OS rate of approximately 14.5-15.3 months with a 39.1-42.5% tumor response rate. In comparison, ICIs have a 12-14 month OS rate with a 26-33% tumor response rate. Given these promising responses, this study evaluates the efficacy of conversion therapy with curative intent following HAIC or ICIs, focusing on survival outcomes. We retrospectively analyzed 80 patients with advanced or TACE-unsuitable intermediate HCC. Patients completed two HAIC or four ICI cycles, followed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria imaging. Based on demographics, cirrhosis status, Barcelona Clinic Liver Cancer classification (BCLC) stage, treatment responses, and treatment modality, survival impacts were analyzed. OS was compared between HAIC and immunotherapy groups. The effect of conversion therapy with curative intent on survival outcomes was analyzed using a Cox regression model. Among the 80 patients, 26 achieved positive response (CR/PR) with HAIC or ICIs, and 9 of them subsequently underwent conversion therapy with curative intent. Key prognostic factors included Child-Pugh stage B vs. A (HR=2.21, p=0.041), BCLC stage C vs. B (HR=4.38, p=0.011), and elevated AFP levels (HR=5.02, p&lt;0.001). Positive responders saw substantial survival benefits (HR=0.26, p=0.001). Patients undergoing conversion therapy exhibited significantly enhanced survival. Median OS was 13.58 months with standard therapy, while the curative intent surgery group did not reach the median OS (p=0.002). For CR/PR patients, 48-month survival was 75.0% for the curative surgery group versus 38.0% for standard treatment. Conversion therapy with curative intent following HAIC or ICIs might enhances survival in patients with advanced or TACE-unsuitable intermediate-stage HCC.

Open Innovation and Regulatory Challenges in New Modality Development: The Pivotal Role of Contract Development and Manufacturing Organisations in Advancing Antibody Drugs.

Ensuring regulatory-compliant manufacturing capability is an essential challenge for new treatment modalities, but its internalisation is not easy for pharmaceutical companies, especially start-ups. This study examines the functions and requirements of contracted development and manufacturing organisations (CDMOs) using the development process of antibody medicines as a case study. Utilizing PubMed, Cortellis and Patent Integration databases, this study delves into publication and contractual trends in monoclonal antibody drugs (mAbs) development, alongside an analysis of patent filings by CDMOs, offering a comprehensive overview of the evolving landscape in mAbs innovation. In the early stages of mAbs development, dedicated bio firms (DBFs) led R&D with superior drug discovery technology but lacked manufacturing capability, which was complemented by CDMOs. This collaboration was an opportunity for CDMOs to expand their capabilities beyond manufacturing technology into antibody drug candidate discovery and structural optimisation technology. From mid-development onwards, it established a technology platform based on these capabilities and developed and established partnerships with existing pharmaceutical companies, including mega pharma. The impact of institutions and regulations on the innovation process was assessed during this development process. These findings are expected to provide valuable insights into the innovation system for new modalities.

An observational study on the efficacy of intralesional steroids in patients with idiopathic granulomatous lobular mastitis in a tertiary care centre

Background: Granulomatous lobular mastitis (GLM) is a rare benign disease of the breast which usually affects young women of childbearing age. The patients usually present with a painful breast mass or with multiple discharging sinuses of breast. Diagnosis is usually established by means of clinical examination followed by radiological, microbiological and histopathological evaluation. The ideal management of patients with GLM is still a matter of debate and treatment modalities such as surgery, systemic and intra-lesional steroids, as well as immunosuppressive agents are being used in clinical practice. In our study, we assessed the clinical response of patients with GLM, treated with intra-lesional steroid injection. Methods: In this prospective observational study, from December 2021 to December 2023, a total of 29 patients who were diagnosed as having GLM and who opted for intra-lesional steroid therapy as the solo treatment, were enrolled. After obtaining informed consent, intra-lesional steroid injection was administered in all the 29 patients. The treatment response was assessed after a period of 3 months from the date of injection. Results: A complete resolution of symptoms and signs was found in majority of the patients (75.9%), 4 (13.8%) had a partial resolution and 2 (6.9%) had persistence of symptoms. One patient (3.4%) was lost to follow up. None had any worsening of symptoms. Conclusions: Intra-lesional steroid can be effectively used in the treatment of GLM and this modality can be completed in a few minutes in an Outpatient setting and is extremely cost effective.

The clinical characteristics and prognosis of patients with acute non-ST-segment elevation myocardial infarction complicated with impaired activity daily living

Abstract Background Impaired activities of daily living (ADL) have been identified as an independent risk factor for cardiovascular diseases. This study aims to describe the clinical characteristics, treatment modalities, and prognosis of acute non-ST-segment elevation myocardial infarction (NSTEMI) patients with impaired ADL. Methods The data for this study were derived from a Health and Medical Big Data Superplatform, comprising a retrospective cohort of patients admitted to and discharged from 72 secondary and tertiary hospitals from 2010 to 2023. The inclusion criteria encompassed patients with a discharge diagnosis of NSTEMI.ADL prior to NSTEMI was evaluated using the Barthel index(BI),a widely used assessment tool for evaluating ADL.The patients' BI were obtained from patients’ resident health records, and patients were categorized into two groups: ADL normal and ADL impaired group. A comparative analysis was conducted between the two groups regarding clinical characteristics, treatment regimens, and prognosis. Results The study included 28,227 NSTEMI patients with normal ADL and 1,576 NSTEMI patients with impaired ADL. Baseline data revealed that the ADL impaired group had a higher proportion of females (49.4% vs. 43.2%, p &amp;lt; 0.001), older age (77.0 [69.0, 83.0] vs. 71.0 [66.0, 78.0], p &amp;lt; 0.001), and a higher proportion of patients with KILLIP III and above (25.86% vs. 17.44%, p &amp;lt; 0.001). Additionally, the ADL impaired group had a greater number of pre-existing comorbidities. Regarding treatment, the proportion of patients undergoing percutaneous coronary intervention (PCI) was significantly lower in the ADL impaired group (16.5% vs. 65.3%, p &amp;lt; 0.001). Moreover, the ADL impaired group showed lower utilization rates of antiplatelet agents, ACEI/ARBs, beta-blockers, ARNI, statins, and nitrates, while the utilization rates of diuretics and cardiac glycosides were higher. In terms of prognosis, the ADL impaired group exhibited a higher in-hospital mortality rate (6.03% vs. 3.35%, p &amp;lt; 0.001). During a median follow-up period of 876 days, the ADL impaired group had significantly higher rates of all-cause mortality (61.2% vs. 35.9%, p &amp;lt; 0.001) and cardiovascular mortality (41.8% vs. 24.8%, p &amp;lt; 0.001), while the rate of revascularization (6.69% vs. 9.20%, p = 0.008) was lower. There were no significant differences in the risks of recurrent non-fatal myocardial infarction (10.7% vs. 10.8%, p = 0.935), recurrent stroke (10.90% vs. 9.48%, p = 0.08), and hemorrhagic stroke (0.82% vs. 0.74%, p = 0.806). Following adjustment for age, gender, KILLIP classification, medical history, and treatment strategies in a multivariable Cox regression analysis, impaired ADL remained an independent risk factor for increased all-cause mortality (aHR 1.167, 95%CI: 1.091-1.249, p &amp;lt; 0.001). Conclusions The decline in ADL is significantly associated with adverse clinical outcomes among NSTEMI patients.Baseline characteristics of patientsMedications of patients

Evaluation of clinical need, effectiveness, and safety of the first myosin inhibitor mavacamten in real world patients

Abstract Background Hypertrophic cardiomyopathy has a high burden of heart failure if obstruction in the left-ventricular outflow tract (HOCM) is present. Mavacamten is the first available myosin inhibitor specifically addressing the underlying pathophysiology of hypercontractility in HOCM. Based on positive results of respective approval studies, mavacamten is recommended for therapy of HOCM in recent ESC guidelines but clinical real world data are lacking. Methods In this ongoing study, consecutive patients with current or previous diagnosis of HOCM presenting at a single referral centre for hypertrophic cardiomyopathy from March 2023 to February 2024 were included and analysed by treatment modality. In patients initiating mavacamten therapy, clinical data of 4 weekly follow ups were assessed, including efficacy (NYHA class, LVOT gradient and biomarkers) and adverse events. Results A total of 72 patients were included (59.1 ± 13.0 years, 68% male). Mavacamten treatment was started in 30/72 (41.7%) patients, 3/72 (4.1%) were referred for transcatheter septal reduction therapy (SRT), and 39/72 (54.2%) did not require any escalation in their treatment due to low gradient with current treatment or few symptoms. Of the latter, 3/39 (7.7%) had previous SRT, 36/39 (92.3%) were stable on negative inotropic medication. The average age of patients selected for mavacamten therapy was 58.0 ± 13.0 years, 80% were male, and the average thickness of the interventricular septum was 18.8 ± 2.8 mm. 22/30 (73.3%) were on baseline therapy with beta-blockers, 3/30 (10.0%) with calcium channel blockers, 2/30 (6.7%) with both, and 4/30 (13.3%) had additional treatment with disopyramide. As shown in table 1, there was a significant decrease in the LVOT gradient under Valsalva maneuver observed 4 weeks after initiation of mavacamten treatment (p=0.006), while the reduction in peak exercise LVOT gradient was statistically significant after 8 weeks (p=0.02). Simultaneously, a significant decrease in Nt-pro-BNP levels was observed after 4 weeks of therapy (p&amp;lt;0.001). A significant drop in troponin T levels compared to baseline was only noted after 20 weeks of treatment (p=0.02). At baseline, 66.7% patients were classified as NYHA class III/IV, and 12.5% after 20 weeks of treatment. 75% of the patients improved ≥1 NYHA class after 20 weeks. Regarding adverse events, there was one case of ejection fraction dropping to &amp;lt;50%, which resolved after halting treatment. Additionally, there were two reports of dizziness and one reported syncope, all of which resolved without taking any actions. Conclusion In this real-world single centre HOCM cohort, 41.7% of patients had an indication for myosin inhibitor therapy. The safety and effectiveness in lowering the LVOT gradient and improving NYHA class were consistent with findings from the approval studies.

Neoadjuvant chemoradiation for down staging of locally-advanced rectal cancer, and assessment of clinical response with digital rectal examination, magnetic resonance imaging and colonoscopy

Background: In this era of total neoadjuvant treatment (TNT) followed by rectal preservation non-operative management (NOM) or wait and watch (WW) approach for non-metastatic locally-advanced rectal cancer (LARC), reliable and reproducible response evaluation to neoadjuvant therapies forms the cornerstone. Through this study, we try to evaluate clinical response of locally-advanced rectal cancer to neoadjuvant chemoradiation (CRT) in terms of downstaging and total mesorectal excision (TME), and the accuracy of digital rectal examination (DRE), magnetic resonance imaging (MRI) and colonoscopy in the assessment of clinical response to neoadjuvant CRT. Methods: Histologically proven locally advanced rectal adenocarcinoma patients, after pretreatment evaluation, were considered for neoadjuvant chemoradiation, i.e., intensity-modulated radiation therapy (IMRT) with 5-fluorouracil (5-FU) and leucovorin-based concurrent chemotherapy. Patients were evaluated 6-8 weeks after completion of CRT and clinical response assessed by means of DRE, colonoscopy and MRI of pelvis. Following surgery, pathological response was assessed on the final histopathological examination (HPE). Results: Twenty-two patients were accrued for this protocol, of which, 15 (68.2%) were male and 7 (31.8%) were female. Downstaging and TME was achieved in 90.9% of the patients. The sensitivity of DRE, colonoscopy and MRI to detect a complete response was 66.67% and specificity was 94.74%. There were no severe toxicities or deaths reported. Conclusions: Neoadjuvant concurrent chemoradiotherapy with bolus 5-FU and leucovorin is an accepted modality of treatment for locoregionally-advanced rectal cancer, which offers higher rates of downstaging and TME. Digital rectal examination, colonoscopy and MRI together can be reliably used to assess response following neoadjuvant CRT.

Association of P2Y12 inhibitor pretreatment strategy with short and long term ischemic and bleeding outcomes in NSTE-ACS patients

Abstract Background and Aims Oral P2Y12 inhibitors form the basis of both short and long term antiplatelet therapy in NSTE-ACS patients. While reducing thrombogenic activity and ischemic risk is the basis of routine P2Y12 inhibitor pretreatment in NSTE-ACS patients, timing of treatment became controversial as a result of studies showing routine P2Y12 inhibitor pretreatment is associated with an increased risk of bleeding. Even though routine pretreatment is no longer recommended in the ESC guidelines, the inadequacies in RCTs combining all treatment modalities have been noted. Our study aims to determine the relationship between P2Y12 inhibitor pretreatment strategy and short and long-term ischemic and bleeding events. Methods The study was designed as a single-center, prospective and observational study. 2602 patients, aged between 18 and 85, diagnosed with NSTE-ACS in accordance with ESC guidelines were included in the study. 2189 patients were administered with P2Y12 inhibitor pretreatment while 413 patients weren't. Demographic data, CVD risk factors, ECG, echocardiography and laboratory findings at the time of admission, interventional procedural details, type of antiplatelet and anticoagulant treatment and application time were recorded. Patients were divided into two groups as pretreatment and no-pretreatment according to the time of administration of P2Y12 inhibitor loading dose. In the no-pretreatment group choice of P2Y12 inhibitor was left to operator in the cath lab before proceeding to PCI. Post-procedural in-hospital and long term follow up (1 year) were obtained through hospital and national registry systems and patient survey. Results In the no-pretreatment group 91.3% of patients underwent coronary angiography and PCI was performed in 51.8%. In patients proceeding to PCI, 58.5% were given clopidogrel and 41.5% were given a potent P2Y12 inhibitor. In the pretreatment group, clopidogrel was the drug of choice in 93.8% of patients. In the pretreatment group, the primary composite endpoint (MACE and bleeding events) were more common during in-hospital follow-up and this difference was due to a significant increase in both BARC class I &amp; II and class III, IV &amp; V bleedings (Table 1). In the long-term follow up, statistically significant difference was only seen in BARC class I &amp; II bleedings in the pretreatment group. There were no difference in MACE rates in neither in-hospital or long-term follow up (Table 2). Also in multivariate regression analysis, pretreatment with a P2Y12 inhibitor was found to be an independent predictor of short term primary composite endpoints and long-term all-cause mortality. Conclusion The results of our study investigating the effects of the P2Y12 inhibitor pretreatment strategy on ischemic and bleeding endpoints in NSTE-ACS patients showed that the pretreatment strategy did not lead to an improvement in MACE rates in in-hospital and long-term follow-up but caused on overall increase in bleeding events.Kaplan-Meier Survival Analysis