Standard Of Care Research Articles

An evaluation of vilobelimab (anti-C5a) as a cost-effective option to treat severely ill mechanically ventilated patients with COVID-19.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. COVID-19 patients in intensive care units (ICUs) requiring invasive mechanical ventilation (IMV) have few available treatment options. PANAMO, a multicenter, double-blind, randomized, placebo-controlled phase 3 study of vilobelimab, which blocks the inflammatory process caused by complement component 5a, demonstrated a significant mortality benefit at 28 and 60 days in these patients. A cost-effectiveness analysis was conducted to assess the incremental cost per quality-adjusted life-year (QALY). A Markov model was used to estimate QALYs and the incremental cost-effectiveness ratio (ICER) of vilobelimab plus standard of care (SOC) versus SOC alone. The model simulated progression from severe COVID-19 to survival or death over a lifetime horizon. Outcomes data (COVID-19 all-cause mortality and renal replacement therapy) were incorporated from the PANAMO trial. COVID-19 mortality estimates were based on Centers for Disease Control and Prevention age-specific survival data. Utility values and hospital costs came from the literature. Vilobelimab cost was obtained from RED BOOK Online. For COVID-19 ICU patients, total costs of care were $103,414 (SOC) and $132,247 (SOC plus vilobelimab), respectively, resulting in an incremental cost of $28,833. SOC provided 6.70 QALYs versus 7.99 QALYs for vilobelimab, an additional 1.29 QALYs. The ICER for vilobelimab plus SOC versus SOC alone was $22,287/QALY. Probabilistic sensitivity analysis demonstrated the robustness of the cost-effectiveness result as vilobelimab plus SOC was favored at a willingness-to-pay threshold of $50,000 in over 81% of iterations. Vilobelimab provides a cost-effective option to treat ICU patients with severe COVID-19 receiving IMV compared to SOC, at well below the commonly accepted $50,000 US willingness-to-pay threshold.

Patient perspectives on health care models in cardiac surgery: a qualitative evaluation

BackgroundThe implementation of ERAS represents a promising solution to improve treatment efficiency and facilitate patient involvement. This innovative care model aims to optimize recovery processes following surgeries by adopting a holistic, interprofessional approach. At our hospital, ERAS was implemented in minimally invasive heart valve surgery, offering two distinct ERAS models. Additionally, there is also the standard of care without ERAS. The objective of the study is to gain insight into patient satisfaction and perceived differences across these various care models.MethodsPatients were interviewed using semi-structured interviews approximately two to three months after undergoing surgery. The data were analysed using qualitative content analysis in accordance with the methodology proposed by Kuckartz. Four main categories were established: Preoperative care, postoperative care and communication, patient participation and involvement, and rehabilitation and post-clinical course.ResultsComprehensive preoperative education and seamless communication throughout the perioperative care journey were identified as fundamental to patient satisfaction and optimal care processes. Patients in the ERAS + model reported higher overall satisfaction with their care compared to patients in the standard of care and ERAS groups.ConclusionPreoperative education establishes the foundation for patients’ subsequent behaviours and expectations regarding their treatment. Physical activity, nutrition, and mental health are significant aspects. The active involvement and participation of patients and their families in the treatment process facilitated superior postoperative care, intensive physiotherapy, mental support, and faster recovery. A functional flow of information throughout the entire care process is vital. Moreover, having a dedicated point of contact had a beneficial impact on patients´ well-being. The integration of innovative ERAS concepts, which encompass interprofessional preoperative patient education and psychosomatic support, represents a promising approach from a patient perspective, offering benefits to a broad spectrum of cardiac surgical patients.

Predictors of wound healing after surgical deroofing in Hidradenitis Suppurativa.

Surgical deroofing is an essential part of ongoing management of Hidradenitis Suppurativa, including persistent lesions non-responsive to medical therapy. The variables associated with delayed wound healing after surgical deroofing are contradictory within the literature due to the inclusion of heterogeneous surgical intervention methods. We aimed to assess the predictors of time to wound healing after surgical deroofing in HS. Patients who underwent in-office surgical deroofing between 2020 and 2024 at a single tertiary HS referral centre were included in analysis. Demographic, disease and blood variables were collected as per standard of care. Statistical analysis was performed using univariate correlation, with multiple regression performed to explore the interactions between variables and identify variables predictive of time to wound healing. A total of 270 individuals were included in the analysis. The median time to wound healing was 9.6 weeks with a range from 4 to 22 weeks. Kaplan-Meier curves demonstrated significant differences with the log rank test when comparing biologic use versus no use, normal versus abnormal CRP and normal versus abnormal haemoglobin. Cox regression analysis identified biologic use with a significant hazard ratio compared to no biologic therapy (HR = 2.512, p < 0.0001) along with baseline CRP (HR = 0.968, p < 0.0001) and baseline haemoglobin (HR = 1.052, p < 0.001). Time to wound healing after in-office deroofing can be decreased with prior biologic therapy and markers of systemic inflammation in blood are also significantly associated with delays in healing. This correlates well with the existing literature promoting concurrent medical and surgical therapy to improve patient outcomes in HS.

The Impact of Next-Generation Sequencing Workflows on Outcomes in Advanced Lung Cancer: A Retrospective Analysis at One Academic Health System.

Broad-based molecular testing with next-generation sequencing (NGS) is now the standard of care in advanced non-small cell lung cancer (NSCLC). Two approaches to molecular testing are (1) reflexive testing at pathologic NSCLC confirmation, often using an in-house molecular panel, and (2) send-out testing to private vendors, ordered by a clinician. This study explored the outcomes with reflex versus send-out testing. A retrospective chart review was conducted of patients diagnosed with de novo stage IV NSCLC in 2019 and 2020 at three hospitals in the same system, one academic hospital (Northwestern Memorial Hospital, or NMH) utilizing reflex, in-house NGS, and two community-based hospitals (Central DuPage Hospital, or CDH, and Delnor, or D) sending out tissue samples for testing. The outcomes assessed were the time from biopsy to results, biopsy to treatment, the incidence of first-line targetable mutations and the use of first-line targeted therapies, and overall survival. In total, 191 patients met the inclusion criteria, 85 at NMH, 106 at CDH + D, and in total, 131 in 2019 and 60 in 2020. The time to results was significantly shorter with reflexive NGS when compared with send-out testing; the time to treatment was also shorter but not statistically significant. At CDH + D, the time to results was significantly shorter with a limited panel than with comprehensive testing, but the time to treatment was similar. NGS testing rates were 95% at NMH and 84.5% at CDH + D (p = 0.009), with 31.0% at NMH receiving 1L targeted therapies versus 20.8% at CDH + D (p = 0.08). In 2019, the median time from biopsy to treatment was 35 days at NMH and 38 days at CDH and Delnor; in 2020, time to treatment was 26 days and 37 days, respectively. Overall survival trended longer in 2020 relative to 2019 independent of site. Reflexive NGS testing is associated with a shorter time to actionable results and higher rates of first-line targetable mutations than send-out testing. In practices with send-out testing, limited panels had slightly faster turnaround times but no difference in time to treatment. If resources allow, reflexive NGS should be considered in healthcare systems for patients with NSCLC.

Adjunct polymeric exclusive enteral nutrition helps achieve biochemical remission in active Crohn’s disease in adults irrespective of disease location and concomitant corticosteroid use

Background and aimData on the effectiveness of polymeric exclusive enteral nutrition (EEN) in inducing biochemical remission in adults with active Crohn’s Disease (CD) is scarce. We aimed to assess the effectiveness of polymeric EEN in inducing biochemical remission in adults with active CD.MethodsSingle-centre retrospective study, from January 2018 to September 2022, of patients with active CD who received therapy with EEN, along with standard of care. Active CD was defined as C-Reactive Protein (CRP) ≥10 mg/L and/or faecal calprotectin (FC) ≥250 µg/g. Primary endpoint (PE) was biochemical remission at 8 weeks. Biochemical remission was defined as CRP &lt;6 mg/L in patients with CRP ≥10 mg/L at baseline and/or FC &lt;150 µg/g in patients with an FC ≥250 µg/g at baseline.Results61 patients were included, 32 (52.4%) female. PE was achieved in 35 (57.4%) patients; 20 (58.8%) with concurrent corticosteroid (CS) and 15 (55.6%) without CS use at baseline, p=1. 43.7% (7/16) of patients with ileal, 50% (4/8) with colonic and 64.9% (24/37) with ileocolonic (p=0.33) disease phenotype achieved PE. Fewer patients with baseline concurrent biological achieved PE (12/29 (41.38%) vs 23/32 (71.9%), p=0.021). On univariable analysis, the absence of biological therapy at baseline was a predictor for achieving PE (OR 3.6 (95% CI 1.23 to 10.6), p=0.019).ConclusionPolymeric EEN is effective in inducing biochemical remission in adults with active CD irrespective of disease location or concurrent CS use. Significantly fewer patients on concurrent biologics at baseline achieved biochemical remission.

Inductive and Deductive Reasoning in Byrom vs. Johns Hopkins Bayview Hospital

The status quo that results from medical malpractice litigation is 85,000 medical malpractice lawsuits filed per year, of which 66% are potentially frivolous. There are also 3 million claims but only 85,000 are represented. There is something wrong with this status quo, which prompts questions about traditional decision-making Traditional decision-making is inductive reasoning. Deductive reasoning is hypothesis testing. The objective evidence and the burden of proof are the same in both; except hypothesis testing has a greater level of confidence. The differences are examined in detail. Of the parties involved in dispute resolution, medical experts are essential, medical experts are doctors. Doctors are familiar with hypothesis testing and threats to validity. Doctors, who are medical experts, are duty-bound to be objective. Hypothesis testing best satisfies this duty. Nothing prohibits medical experts from using hypothesis testing when they review a case to arrive at an opinion; although, until now, none do. Yet, as doctors, it is expected of them and they can never be prohibited from doing so. In the final analysis, traditional decision-making subjectively infers a departure from the standard of care; however, hypothesis testing objectively proves it.

Treatment Strategies Used in Treating Myelofibrosis: State of the Art

Background: Current drug therapy for myelofibrosis does not alter the natural course of the disease or prolong survival, and allogeneic stem cell transplantation is the only curative treatment modality. For over a decade, the Janus kinase (JAK) inhibitor ruxolitinib has been the standard of care. More recently, newer-generation JAK inhibitors have joined the ranks of accepted treatment options. Objectives: The primary goal of treatment is to reduce spleen size and minimize disease-related symptoms. Prognostic scoring systems are used to designate patients as being at lower or higher risk. For transplant-eligible patients, transplant is offered to those with a bridge of a JAK inhibitor; patients who are not eligible for transplant are usually offered long-term therapy with a JAK inhibitor. Limited disease-modifying activity, dose-limiting cytopenias, and other adverse effects have contributed to discontinuation of JAK inhibitor treatment. Conclusions: Novel JAK inhibitors and combination approaches are currently being explored to overcome these shortcomings. Further research will be essential to establish optimal therapeutic approaches in first-line and subsequent treatments.

A randomized control trial evaluating the advice of a physiological-model/digital twin-based decision support system on mechanical ventilation in patients with acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is highly heterogeneous, both in its clinical presentation and in the patient's physiological responses to changes in mechanical ventilator settings, such as PEEP. This study investigates the clinical efficacy of a physiological model-based ventilatory decision support system (DSS) to personalize ventilator therapy in ARDS patients. This international, multicenter, randomized, open-label study enrolled patients with ARDS during the COVID-19 pandemic. Patients were randomized to either receive active advice from the DSS (intervention) or standard care without DSS advice (control). The primary outcome was to detect a reduction in average driving pressure between groups. Secondary outcomes included several clinically relevant measures of respiratory physiology, ventilator-free days, time from control mode to support mode, number of changes in ventilator settings per day, percentage of time in control and support mode ventilation, ventilation- and device-related adverse events, and the number of times the advice was followed. A total of 95 patients were randomized in this study. The DSS showed no significant effect on average driving pressure between groups. However, patients in the intervention arm had a statistically improved oxygenation index when in support mode ventilation (-1.41, 95% CI: -2.76, -0.08; p = 0.0370). Additionally, the ventilatory ratio significantly improved in the intervention arm for patients in control mode ventilation (-0.63, 95% CI: -1.08, -0.17, p = 0.0068). The application of the DSS led to a significantly increased number of ventilator changes for pressure settings and respiratory frequency. The use of a physiological model-based decision support system for providing advice on mechanical ventilation in patients with COVID-19 and non-COVID-19 ARDS showed no significant difference in driving pressure as a primary outcome measure. However, the application of approximately 60% of the DSS advice led to improvements in the patient's physiological state. clinicaltrials.gov, NCT04115709.

Effectiveness of multifaceted interventions including motivational interviewing and home-based rehabilitation program for improving mental and physical health in stroke patients: A randomized controlled trial

BackgroundIn Vietnam, early screening and intervention for post-stroke mental health are limited, with rising demand for home-based rehabilitation due to the scarcity of inpatient programs. ObjectivesWe aimed to evaluate the effectiveness of multifaceted interventions, including Motivational Interviewing and home-based rehabilitation, in improving the mental and physical health of stroke patients. DesignA randomized controlled trial at the Vietnam National Geriatric Hospital assessed a multi-intervention approach for stroke survivors from 2021 to 2022. Ninety-two participants (aged over 45 with a stroke diagnosis) were randomly assigned to an intervention group (Motivational Interviewing and home-based rehabilitation) or a control group (standard care), with 46 participants in each group. Outcomes for mental health (Patient Health Questionnaire-9, Fatigue Severity Scale, Mini-Mental State Examination) and physical health (Barthel Index) were measured at baseline and after 1, 3, and 6 months. Statistical analyses used t-tests, Cohen's d, and repeated measures ANOVA. ResultsOver 6 months, 37 participants completed the intervention program. Baseline characteristics were similar except for age, lesion locations, and National Institutes of Health Stroke Scale scores. The intervention group showed significant improvements in mental health and physical function. Patient Health Questionnaire-9 scores decreased from 9.1 to 1.8, and Fatigue Severity Scale scores dropped from 28.5 to 17.8, while Barthel Index scores improved from 58.8 to 68.8 (p < 0.001). ConclusionsWe found that participants who underwent Motivational Interviewing therapy and home-based rehabilitation were more likely than those receiving standard care to experience substantial improvements in both mental and physical health metrics. RegistrationThe research protocol was registered on ClinicalTrials.gov on August 1, 2021 (Identifier: NCT04941482, link: https://clinicaltrials.gov/study/NCT04941482).

Forimtamig, a novel GPRC5D targeting T cell bispecific antibody with 2+1 format for the treatment of multiple myeloma

Despite several approved therapies, multiple myeloma (MM) remains an incurable disease with high unmet medical need. “Off-the-shelf” T-cell bispecific antibodies (TCBs) targeting BCMA and GPRC5D have demonstrated high objective response rates (ORR) in heavily pre-treated MM patients, however, primary resistance, short duration of response and relapse driven by antigen shift frequently occurs. Although GPRC5D represents the most selective target in MM, recent findings indicate antigen loss occurs more frequently than with BCMA. Thus, anti-GPRC5D immunotherapies must hit hard during a short period of time to kill as many myeloma cells as possible. Here, we characterize forimtamig, a novel GPRC5D-targeting TCB with 2+1 format, using preclinical models of MM. Bivalent binding of forimtamig to the N-terminus of GPRC5D confers higher affinity as compared to classical 1+1 TCB formats correlating with formation of more stable immunological synapses and higher potency in tumor cell killing and T cell activation. Using an orthotopic mouse model of MM, forimtamig recruited T effector cells to the bone marrow and induced rapid tumor killing even after the introduction of step-up dosing to mitigate cytokine release. Combination of forimtamig with standard-of-care (SoC) agents including anti-CD38 antibodies, immunomodulatory drugs and proteasome inhibitors improved depth and duration of response. The combination of forimtamig with novel therapeutic agents including BCMA-TCB and Cereblon E3 Ligase Modulatory Drugs (CELMoDs) was potent and prevented occurrence of GPRC5D-negative tumor relapse. Forimtamig is currently being evaluated in Phase 1 clinical trials in relapsed and refractory myeloma (RRMM) patients for monotherapy and in combination treatments. NCT04557150

Adding Metastasis-Directed Therapy to Standard-of-Care Systemic Therapy for Oligometastatic Breast Cancer (EXTEND): a Multicenter, Randomized Phase II Trial

PurposePrior evidence suggests a progression-free survival (PFS) benefit from adding metastasis-directed therapy (MDT) to standard-of-care (SOC) systemic therapy for patients with some oligometastatic solid tumors. Randomized trials testing this hypothesis in breast cancer have yet to be published. We sought to determine whether adding MDT to SOC systemic therapy improves PFS in oligometastatic breast cancer. MethodsEXTEND is a multicenter phase II randomized basket trial testing the addition of MDT to SOC systemic therapy in patients with ≤5 metastases (NCT03599765). Patients were randomized 1:1 to MDT (definitive local treatment to all sites of disease, plus SOC systemic therapy) or to SOC systemic therapy only. Primary endpoint was PFS, and secondary endpoints included overall survival (OS), time to subsequent line of systemic therapy, and time to the appearance of new metastases. Exploratory analyses included quality of life (QOL) and systemic immune response measures. ResultsFrom September 2018 through July 2022, 22 and 21 patients were randomized to the MDT and no-MDT arms, respectively. At a median follow-up of 24.8 months, PFS was not improved with the addition of MDT to SOC systemic therapy (median PFS 15.6 months MDT vs 24.9 months no-MDT [hazard ratio {HR} 0.91; 95% CI 0.34–2.48, p=0.86]). Similarly, MDT did not improve OS, time to subsequent line of systemic therapy, or time to the appearance of new metastases (all p>0.05). No significant differences were found in QOL measures, systemic T-cell activation, or T-cell stimulatory cytokine concentration. ConclusionAmong patients with oligometastatic breast cancer, the addition of MDT to SOC systemic therapy did not improve PFS. These findings suggest that MDT may have no systemic benefit in otherwise unselected oligometastatic breast cancer patients, although this trial was limited by a heterogenous and small sample size and overperformance of both treatment arms.

A Comprehensive Blood Bank Management System:Optimizing Donor and Inventory Tracki

An essential part of today's healthcare infrastructure is the Blood Bank Management System (BBMS), which makes sure that blood donations, inventories, and distribution are managed effectively and efficiently. This study provides a thorough examination of BBMS, stressing its salient characteristics, range of applications, and effects on blood bank operations. The study looks into how BBMS implementation can boost patient care, increase overall blood bank efficiency, and lead to better healthcare outcomes. This paper offers important insights into the role of technology in blood bank management through a combination of literature review, system development, and evaluation. Because they offer a consistent supply of blood products for transfusions, surgeries, and medical treatments, blood banks are essential to healthcare systems. However, issues like inventory shortages, waste, and human error are common with traditional blood bank management procedures. This paper's introduction addresses the importance of effective blood bank management and poses the following research question: Howcan blood bank operations be made more effective and efficient with the use of a blood bank management system? The study intends to advance blood bank management techniques and the general standard of patient care by addressing this question.

NPR1 promotes cisplatin resistance by inhibiting PARL-mediated mitophagy-dependent ferroptosis in gastric cancer

Cisplatin-based chemotherapy serves as the standard of care for individuals with advanced stages of gastric cancer. Nevertheless, the emergence of chemoresistance in GC has detrimental impacts on prognosis, yet the underlying mechanisms governing this phenomenon remain elusive. Level of mitophagy and ferroptosis of GC cells were detected by fluorescence, flow cytometry, GSH, MDA, Fe2+ assays, and to explore the specific molecular mechanisms between NPR1 and cisplatin resistance by performing western blot and coimmunoprecipitation (co-IP) assays. These results indicates that NPR1 positively correlated with cisplatin-resistance and played a crucial part in conferring resistance to cisplatin in gastric cancer cells. Mechanistically, NPR1 affected levels of mitophagy and ferroptosis in human cisplatin-resistance GC cells with cisplatin treatment. Specifically, NPR1 inhibited mitophagy-dependent ferroptosis by reducing the ubiquitination-mediated degradation of PARL; moreover, NPR1 promoted PARL stabilization by disrupting the PARL–MARCH8 complex, which ultimately led to the development of chemoresistance in GC cells. Considering our findings, NPR1 appears to play an important role in chemotherapy for GC. NPR1 could potentially be used to overcome chemotherapy resistance.Graphical 1. NPR1 is highly expressed in cisplatin-resistant GC cells and promotes the cisplatin resistance.2. According to IP-MS, NPR1 inhibits mitophagy-dependent ferroptosis through its downstream protein PARL.3. NPR1 promoted PARL stabilization by disrupting the PARL–MARCH8 complex to inhibit the ubiquitination-mediated degradation of PARL.

POST‐UK (Adjunctive Intra‐Arterial Urokinase After Successful Endovascular Thrombectomy in Patients With Large‐Vessel Occlusion Stroke): Study Protocol of a Multicenter, Prospective, Randomized, Open‐Label, Blinded‐End Point Trial

BACKGROUND Intra‐arterial infusion of an adjunctive thrombolytic agent after macrovascular recanalization by endovascular thrombectomy was regarded as a promising strategy to promote outcomes of patients with stroke. Given the characteristics of urokinase as an affordable, available, and widely applied medication, especially in Eastern countries, this trial aims to assess the safety and efficacy of intra‐arterial urokinase as adjunct to endovascular thrombectomy in improving outcomes among patients with anterior large‐vessel occlusion stroke after excellent to complete reperfusion. METHODS The POST‐UK (Adjunctive Intra‐Arterial Urokinase After Successful Endovascular Thrombectomy in Patients With Large Vessel Occlusion Stroke) trial is a multicenter, prospective, randomized, open‐label, blinded‐end point trial conducted in China. The planned sample size is 498. Those eligible patients with anterior circulation large‐vessel occlusion stroke and achieving excellent to complete reperfusion by endovascular thrombectomy are planned to be consecutively randomized in a 1:1 ratio to the experimental group (a single dose of intra‐arterial urokinase) or to standard of care. RESULTS The primary outcome is a freedom from disability (modified Rankin Scale score of 0–1) at 90±7 days. The safety outcomes are mortality within 90±7 days and symptomatic intracranial hemorrhage within 48 hours. CONCLUSION The POST‐UK trial will provide valuable insight of efficacy and safety of intra‐arterial urokinase in patients with large‐vessel occlusion stroke after achieving excellent to complete reperfusion by endovascular thrombectomy.

Overcoming genetic neuromuscular diagnostic pitfalls in a middle-income country.

Neuromuscular disorders affect almost 20 million people worldwide. Advances in molecular diagnosis have provided valuable insights into neuromuscular disorders, allowing for improved standards of care and targeted therapeutic approaches. Despite this progress, access to genomic diagnosis remains scarce and inconsistent in middle-income countries such as Brazil. The lack of public health policies to enable feasible genetic diagnosis and the shortage of neuromuscular disorders specialists are the main reasons in this process. We report our experience in a transcontinental genomic consortium for neuromuscular disorders highlighting how collaborative efforts have helped overcome various obstacles in diagnosing our patients. We describe several challenging cases categorized into three major themes, underlining significant gaps in genetic diagnosis: (i) reverse phenotyping and variant validation, (ii) deep phenotyping and identifying a bespoke molecular approach, and (iii) exploring the use of genomic tests beyond whole exome sequencing. We applied a qualitative case-based approach to exemplify common pitfalls in genomic diagnosis in a middle-income country. Our experience has shown that establishing a virtual transcontinental partnership is viable, offering effective exchange of scientific experiences, providing both guidance for rational decision-making and specialized training on a local level and access to diverse molecular diagnosis strategies and functional analyses. Collaborative efforts such as these have the potential to overcome local obstacles, strengthen scientific capabilities, foster diverse multi-ethnic cohorts, and ultimately provide improved care for patients.

Outcome and survival analysis of pulmonary metastasectomy for primary sarcoma with pulmonary metastases.

Sarcomas are rare malignancies, accounting for approximately 1% of all cancers. Pulmonary metastases are the most preferential site for distant metastasis in malignant soft tissue sarcomas. Despite the lack of evidence from large randomized trials to support treatment guidelines, surgical resection of resectable metastatic tumors remains the current standard of care. This study aimed to explore the survival status of patients with soft tissue sarcoma after resection of pulmonary metastases. This study is a retrospective analysis of patients who mestastasectomy by means of lobar or sublobar resections at National Taiwan University Hospital and its branches. The statistical and investigation period was from February 2007 to December 2020. Among 110 samples during the investigation period, the overall 5-year survival rate was 62.9%, which was higher than the 15%-50.9% reported previously. A disease-free interval of more than 12 months and the occurrence of local recurrence of sarcoma at the time of resection of pulmonary metastases are associated with overall survival. Most of the samples were treated with minimally invasive surgery (VATS), and therefore, most patients had a shorter hospital stay and better postoperative recovery. For pulmonary metastatic sarcoma, pulmonary metastasectomy is a relatively safe treatment method with short hospital stay and short ICU stay. The results of this study suggest that VATS is preferred over thoracotomy, but further observations are needed to confirm these findings.

Detection of a Water-Soluble Hypericin Formulation in Glioblastoma Tissue with Fluorescence Lifetime and Intensity Using a Dual-Tap CMOS Camera System.

High hypericin-loaded polyvinylpyrrolidone (HHL-PVP) constitutes a novel approach to utilize the promising characteristics of hypericin for photodynamic diagnosis (PDD) and therapy (PDT) of brain tumors in an orally bioavailable formulation. The aim of this study was to investigate the ability of a Complementary Metal-Oxide-Semiconductor (CMOS) camera-based fluorescence imaging system to selectively visualize HHL-PVP in glioblastoma tissue even in the presence of 5-Aminolvevulinic acid (5-ALA) induced fluorescence, which is widely utilized in brain tumor surgery. We applied a previously established system with a non-hypericin specific filter for 5-ALA fluorescence visualization and a newly introduced hypericin-specific filter at 575-615 nm that transmits the spectrum of hypericin, but not 5-ALA fluorescence. Glioblastoma specimens obtained from 12 patients (11 with preoperative 5-ALA intake) were ex vivo incubated with HHL-PVP. Subsequently, fluorescence intensity and lifetime changes using both the non-hypericin specific filter and hypericin-specific filter were measured before and after HHL-PVP incubation and after subsequent rinsing. While no significant differences in fluorescence signal were observed using the non-hypericin specific filter, statistically significant increases in fluorescence intensity (p = 0.001) and lifetime (p = 0.028) after HHL-PVP incubation were demonstrated using the hypericin-specific filter. In consequence, specimens treated with HHL-PVP could be identified according to the fluorescence signal with high diagnostic sensitivity (87.5%) and specificity (100%). Our CMOS camera-based system with a hypericin-specific filter is capable of selectively visualizing hypericin fluorescence in glioblastoma tissue after ex vivo HHL-PVP incubation. In the future, this technique could facilitate clinical investigations of HHL-PVP for PDD and PDT while maintaining the current standard of care with 5-ALA guidance.

Impact of a Clinical Decision Support System on the Change over Time in the Anticholinergic Load in Geriatric Patients: The SADP-Antichol Study

Purpose: Anticholinergic drugs can cause adverse events (AEs) in older adults. Clinical decision support systems (CDSSs) can detect prescriptions with a high anticholinergic load. Our starting hypothesis was that the anticholinergic load could be reduced by combining a CDSS with a strategy for generating pharmacist interventions. The objective of the present study was to assess the impact of this combination on the change over time in the anticholinergic load in hospitalized older adults. Methods: This prospective, single-centre study was divided into two 6-week periods. During the interventional period, a pharmacist analyzed the alerts generated by the CDSS for 30 targeted anticholinergic drugs and decided whether to issue a pharmacist intervention. A control period corresponds to standard care. The primary endpoint of the study is the delta of the anticholinergic load between the alert and hospital discharge; the secondary endpoint is the incidence of anticholinergic adverse events (AEs). Results: Of the 144 alerts generated, 87 were considered to be relevant (36 in the interventional period and 51 in the control period). A significant difference was observed between the delta anticholinergic load between the experimental and control periods (1.61 vs. 0.67, p-value = 0.0115). For the targeted drugs (n = 94) over the 87 alerts, 46.8% were for antihistamines and 21.3% were for desloratadine. Of the 36 pharmacist interventions sent by the pharmacist, 19 (52.8%) were accepted. The most deprescribed drug class was the antihistamine class (n = 7), and the most deprescribed drug was amitriptyline (n = 5). Among these 87 patients with alerts, the correlation between the anticholinergic load and the number of AEs was not statistically significant (p = 0.887). The most common AE affecting the peripheral nervous system was constipation (28.6%), and the most common AE affecting the central nervous system was confusion (29.9%). Conclusions: Our results showed that the combination of specific CDSS rules with pharmacist-mediated risk management procedures could further reduce the anticholinergic load in hospitalized older adults, relative to routine care. It remains to be determined whether this reduction in the anticholinergic load has an impact on the incidence of peripheral and central anticholinergic AEs, and thus the health of these patients.

Surgery With or Without Radiotherapy Versus Radiotherapy Alone for Malignant Spinal Cord Compression: An Updated Meta-analysis.

A systematic review and meta-analysis. To conduct a meta-analysis of studies that compared surgery with or without radiotherapy to radiotherapy alone for patients with malignant spinal cord compression, and a subgroup analysis of patients stratified by hematologic and solid malignancies. Two previous meta-analyses showed that surgery with or without radiotherapy was better than radiotherapy alone in patients with malignant spinal cord compression. Nevertheless, there was no stratification by tumor type, leading to uncertainty regarding best approach for patients with hematologic malignancies. We searched PubMed, Scopus, and Web of Science, for studies comparing surgery with or without radiotherapy to radiotherapy alone in patients with malignant spinal cord compression. The primary outcomes were improvement in ambulatory status and survival at 12 months. For neurological outcomes, we included studies involving both locally advanced primary malignancies of the spine and metastatic tumors. We restricted our analysis to studies on metastases for survival outcomes. We included 2536 patients from 18 studies. Surgery was performed in 890 (35%) patients. The pooled analysis of all studies revealed that improvement in ambulatory status (OR 2.65; 95% CI 1.60-4.39) and survival at 12 months (OR 1.66; 95% CI 1.10-2.52) were significantly higher in patients who underwent surgery with or without radiotherapy. Improvement in ambulatory status (OR 1.92; 95% CI 1.19-3.09) and survival at 12 months (OR 4.24; 95% CI 2.35-7.66) were significantly higher in patients with hematologic malignancies in the surgical arm. The primary outcomes were not significantly different between patients with solid malignancies. Surgical intervention demonstrates superior neurological outcomes and increased survival compared with radiotherapy alone. Subgroup analysis revealed that patients with hematologic malignancies on surgery group experienced superior primary outcomes; however, high risk of bias of the included studies preclude definitive changes in standard care based on this data. These findings underscore the need for further research regarding the efficacy of surgical versus radiotherapeutic approaches for specific tumor types. 2.

Effect of aluminum foil reflector on serum bilirubin and duration of phototherapy among term neonates undergoing phototherapy for hyperbilirubinemia: A randomized controlled trial

Background: Jaundice is a common clinical issue especially in the first week of life and one of the leading causes for readmission to the hospital. This study aimed to assess the effect of aluminium foil reflector on serum bilirubin level ,duration of phototherapy and duration of hospital stay. Methods: A randomized controlled trial was carried among 50 term neonatesin neonatal intensive care unit(NICU) .Term neonates were randomly assigned in to experimental and control group by block randomization. Consecutive sampling technique was used to enroll the neonates who met the inclusion criteria. During photo therapy neonates in the control group received standard careand the neonatesin the experimental group received standard care along with aluminium foil reflector around all the four sides of neonatal cot. Data were analysed using chi square test, fisher exact test and independentt-test. Results: After the intervention the serum bilirubin levels in the experimental and control groupswere13.20±3.35 and 14.07±3.12 respectively (P = 0.348),total duration of phototherapy in hours in experimental group and control groupswere 35.76±17.20 and 38.08±16.36 respectively(P = 0.627) and duration of hospital stay in days in experimental group and control group were 2.6±0.91 and 2.92±1.22 respectively (P = 0.299). Conclusion: Aluminium foil reflector aids in decreasing bilirubin level, reduced the duration of phototherapy and duration of hospital stay among term neonates.