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Pancreatic cancer is the most lethal common solid malignancy. Systemic therapies are often ineffective, and predictive biomarkers to guide treatment are urgently needed. We generated a pancreatic cancer patient-derived organoid (PDO) library that recapitulates the mutational spectrum and transcriptional subtypes of primary pancreatic cancer. New driver oncogenes were nominated and transcriptomic analyses revealed unique clusters. PDOs exhibited heterogeneous responses to standard-of-care chemotherapeutics and investigational agents. In a case study manner, we found that PDO therapeutic profiles paralleled patient outcomes and that PDOs enabled longitudinal assessment of chemosensitivity and evaluation of synchronous metastases. We derived organoid-based gene expression signatures of chemosensitivity that predicted improved responses for many patients to chemotherapy in both the adjuvant and advanced disease settings. Finally, we nominated alternative treatment strategies for chemorefractory PDOs using targeted agent therapeutic profiling. We propose that combined molecular and therapeutic profiling of PDOs may predict clinical response and enable prospective therapeutic selection.Significance: New approaches to prioritize treatment strategies are urgently needed to improve survival and quality of life for patients with pancreatic cancer. Combined genomic, transcriptomic, and therapeutic profiling of PDOs can identify molecular and functional subtypes of pancreatic cancer, predict therapeutic responses, and facilitate precision medicine for patients with pancreatic cancer. Cancer Discov; 8(9); 1112-29. ©2018 AACR.See related commentary by Collisson, p. 1062This article is highlighted in the In This Issue feature, p. 1047.

Poor linkage, engagement and retention remain significant barriers in achieving HIV treatment goals in the US. HIV-infected persons entering or re-entering care across three Southern California academic HIV clinics, were randomized (1:1) to an Active, Linkage, Engagement, Retention and Treatment (ALERT) specialist for outreach and health coaching, or standard of care (SOC). The primary outcome of time to loss to follow up (LTFU) was compared using Cox proportional hazards regression modeling. No differences in the median time to LTFU (81.7 for ALERT versus 93.6 weeks for SOC; HR 1.27; p = 0.40), or time to ART initiation was observed (N = 116). Although, ALERT participants demonstrated worsening depressive symptomatology from baseline to week 48 compared to SOC (p = 0.02). The ALERT intervention did not improve engagement and retention in HIV care over SOC. Further studies are needed to determine how best to apply resources to improve retention and engagement.

BackgroundThe number of active opioid analgesic prescriptions has risen steadily, causing increases in nonmedical opioid use, addiction, and overdose. Insufficient focus on patient discharge instructions has contributed to lack of patient awareness regarding dangers of opioids. This study examines whether an educational Khan Academy-style animation discharge instruction on the dangers and safe usage of opioid analgesics elicits higher knowledge acquisition than current standard of care. Additionally, it measures the feasibility of implementing this video discharge instruction in the emergency department (ED).MethodsFifty-two English-speaking patients aged 18 years or older receiving an opioid prescription were enrolled in this study. Patients were randomized into 2 groups. The standard of care group received verbal instruction and an informational sheet, whereas the video animation group received a 6-minute video on proper usage of opioids in addition to standard of care. Video content was sourced from samhsa.gov and administered within the ED prior to discharge. Both groups received a 26-question test regarding the dangers and safe usage of opioids immediately after education. An unpaired t test compared knowledge acquisition between the 2 groups.ResultsFifty-four patients were approached, 52 patients enrolled; 27 in the standard group and 25 in the animation group. The standard of care group averaged 65% knowledge acquisition (16.8/26 correct), whereas the animation group averaged 82% acquisition (21.2/26 correct). The video animation significantly increased patient knowledge acquisition about opioid medications' risks and proper usage and disposal (P = .001).ConclusionIt can be concluded that medical knowledge acquisition is improved in the video animation group compared with the current standard of care (P = .001). It can also be concluded that it is feasible to implement a novel media platform to educate patients receiving opioid analgesics in the ED (96.1%).

Abstract Background Minimally invasive breast biopsy (MIBB) is the standard of care for the diagnosis of breast cancer, with consensus guidelines suggesting MIBB goals of 90% of total biopsies. In a previous study of patients in the rural state of Vermont, USA (population size of 640,000), rural breast cancer patients had open biopsies 42% of the time compared to 29% of urban breast cancer patients. The aim of this study was to assess overall population‐based biopsy trends in Vermont. Methods The Vermont Breast Cancer Surveillance System (VBCSS) was used to identify women receiving MIBB and excisional breast biopsies in Vermont. Patient zip code at the time of initial biopsy was used to determine the patient residence rurality by rural–urban commuting area codes (RUCA 2.0™). Results There were 9122 diagnostic episodes from 1999 to 2018. MIBB was the initial biopsy method in 7524 (82.5%) cases, while surgical excision was the initial biopsy method in 1598 (17.5%) cases. A linear trend fit estimated an increase of 1.3% per year (p

Objective: HER-MES was the first head-to-head, phase 4 trial to assess the tolerability and effectiveness of erenumab against standard of care treatment (topiramate). This post hoc analysis compared the efficacy of erenumab with topiramate in patients who completed the trial on study medication. Methods: Post hoc sensitivity analysis was performed using the full analysis set. Outcomes assessed included the proportion of patients with a ≥50% reduction in monthly migraine days (MMD) from baseline (50% responder rate), over the last 3 months (months 4, 5, and 6) of the double-blind treatment phase (DBTP), the 50% responder rate during the first month of the DBTP, and change from baseline in MMD during the DBTP. Multiple imputation was done for efficacy values of patients who discontinued study treatment. Results: Patients (N = 777) were randomly assigned (1:1) to either 70 or 140 mg/month erenumab (N = 389) or 50–100 mg/day topiramate (N = 388). Of these, 334 patients (85.9%) receiving erenumab, and 231 patients (59.5%) receiving topiramate completed the DBTP on study medication. Patients on study medication until the end of the DBTP received a mean dose of 119 mg/month for erenumab and 92 mg/day for topiramate. At month 1, a significantly greater proportion of patients receiving erenumab (39.2%) reported ≥50% reduction in MMD from baseline compared with those receiving topiramate (24.0%; p < 0.001). In the last 3 months, a significantly larger proportion of patients receiving erenumab (60.3%) achieved ≥50% reduction in MMD from baseline compared with those receiving topiramate (43.3%; p < 0.001). Patients receiving erenumab demonstrated significantly greater reductions in MMD during the last 3 months from baseline versus those receiving topiramate (− 6.13 vs − 4.90; 95% CI: − 1.87 to − 0.61; p < 0.001). Conclusions: This post hoc analysis demonstrated significantly superior efficacy of erenumab versus topiramate in achieving a ≥50% reduction in MMD with an early onset of efficacy. Trial registration: ClinicalTrials.gov NCT03828539. [ABSTRACT FROM AUTHOR]

Introduction: The social worker (SW) role in the Hemophilia Treatment Center (HTC) is complex and broad, providing direct support, spanning across micro, mezzo and macro levels of care. Aim: Research demonstrates discrepancy between actual and ideal SW roles among the HTC SW community. Soliciting perceptions from HTC staff about the SW role can provide a deeper understanding of this discrepancy and improve collaboration amongst care team members in meeting the psychosocial needs of HTC patients. Methods: Funded by the National Hemophilia Foundation (NHF), a national online survey was conducted in 2020 to determine the views and attitudes of what the SW role is by HTC staff. Separate surveys were emailed to active HTC SWs and staff to collect anonymous data. Demographics of SWs gathered included age, education, years of practice, full time equivalent (FTE) status, and caseload. All disciplines were asked questions about perceptions, barriers, and potential ways to enhance and strengthen the SW role within HTCs. Results: Results demonstrated that subcategory‐oriented questions (40 in total) and qualitative responses highlighted diverse viewpoints and offered clarity about these differences. Conclusion: Findings indicated most HTC staff value the multi‐faceted role of SW at their centres, and both groups identified time, limited resources, and role confusion as barriers to utilizing SW services. Outcomes will inform the development of a "standards of practice" tool that will provide education for HTC staff, patients, and families, and serve as an empowerment tool for SW to highlight their skillset and define their role. [ABSTRACT FROM AUTHOR]

BackgroundThe high rate of attrition along the care cascade of infection with human immunodeficiency virus (HIV) results in lost opportunities to provide timely antiretroviral therapy (ART) and to prevent unnecessarily high mortality. This study aims to assess the effectiveness of a structural intervention, the one-stop ("One4All") strategy that streamlines China's HIV care cascade with the intent to improve testing completeness, ART initiation, viral suppression, and mortality.MethodA two-arm, cluster-randomized controlled trial was implemented in twelve county hospitals in Guangxi China to test the effectiveness of the One4All strategy (intervention arm) compared to the current standard of care (SOC; control arm). The twelve study hospitals were selected for homogeneity and allocated one-to-one to the intervention and control arms. All patients screening HIV positive in study hospitals were enrolled. Target study enrollment was 180 participants per arm, 30 participants per hospital. Basic demographic information was collected as well as HIV risk behavior and route of infection. In intervention hospitals, patients then went on to receive point-of-care CD4 testing and in-parallel viral load (VL) testing whereas patients in control hospitals progressed through the usual SOC cascade. The primary outcome measure was testing completeness within 30 days of positive initial HIV screening result. Testing completeness was defined as receipt of all tests, test results, and post-test counseling. The secondary outcome measure was ART initiation (receipt of first ART prescriptions) within 90 days of positive initial HIV screening result. Tertiary outcome measures were viral suppression (≤200 copies/mL) and all-cause mortality at 12 months.DiscussionWe expect that this first-ever, cluster-randomized controlled trial of a bundle of interventions intended to streamline the HIV care cascade in China (the One4All strategy) will provide strong evidence for the benefit of accelerating diagnosis, thorough clinical assessment, and ART initiation via an optimized HIV care cascade. We furthermore anticipate that this evidence will be valuable to policymakers looking to elevate China's overall HIV/AIDS response to meet the UNAIDS 90-90-90 targets and the broader, global goal of eradication of the HIV/AIDS epidemic.Trial registrationClinicalTrials.gov # NCT02084316 . (Registered on March 7, 2014).

Background: Point-of-care ultrasound (POCUS) has been reported as a valuable tool for bedside diagnoses of abdominal Aortic Aneurysms (AAA). However, no data exist regarding POCUS in measuring follow-up AAA diameter studies in patients with existing AAAs. The purpose of this study was to determine the variability of aortic measurements performed by a non-physician using POCUS vs standard of care (SOC) measurements by a registered vascular technologist or an abdominal/pelvic CT scan. Methods: A prospective observational ultrasound study was performed from 1/1/2019 to 3/31/2021 on patients with a diagnosis of an AAA (≥3.0 cm). A research coordinator (non-physician) underwent a 3-hour training session in ultrasound operation and basic human anatomy to measure AAA diameter. The maximum aortic diameter was documented and compared to measurements obtained by SOC ultrasonography or CT scan. The POCUS and SOC ultrasounds were separated by no more than 90 days. Clinical risk factors including age, race, body mass index, coronary artery disease, hypertension, peripheral vascular disease, cerebrovascular disease, diabetes, and current smoking were also collected. Results: Eighty-one patients (mean age: 73.6 ± 5.8 years, body mass index: 29.5 ± 6.2 kg/m2) were being followed in a vascular clinic and underwent both a POCUS and SOC ultrasounds. One indeterminant study was reported in identifying an AAA diagnosis, due to an overlying colostomy. The average follow-up time from initial screening aortic diameter to POCUS was 4.4 ± 3.7 years. Overall average aortic diameter measurements obtained were 4.1 ±.9 cm for POCUS and 4.0 ±.9 cm for SOC (P = NS). Average difference in aortic measurement for POCUS and SOC was −.1 ±.3 cm. Conclusions: POCUS is an accurate method to follow AAA diameter in patients. POCUS could improve patient follow up with AAA diameter measurements, streamline care and reduce overall burden for both patients and Radiology Departments in assessing follow up AAA diameters. [ABSTRACT FROM AUTHOR]

The technical standards in anesthesiology govern the professional practice and allow for the provision of safer anesthesia and surgery. This article gives a historical perspective on the creation, main content, and consequences of the implementation of the Peruvian standards in anesthesiology. [ABSTRACT FROM AUTHOR]

Despite several new therapeutic options for acute myeloid leukemia (AML), disease relapse remains a significant challenge. We have previously demonstrated that augmenting ceramides can counter various drug‐resistance mechanisms, leading to enhanced cell death in cancer cells and extended survival in animal models. Using a nanoscale delivery system for ceramide (ceramide nanoliposomes, CNL), we investigated the effect of CNL within a standard of care venetoclax/cytarabine (Ara‐C) regimen. We demonstrate that CNL augmented the efficacy of venetoclax/cytarabine in in vitro, ex vivo, and in vivo models of AML. CNL treatment induced non‐apoptotic cytotoxicity, and augmented cell death induced by Ara‐C and venetoclax. Mechanistically, CNL reduced both venetoclax (Mcl‐1) and cytarabine (Chk1) drug‐resistant signaling pathways. Moreover, venetoclax and Ara‐C augmented the generation of endogenous pro‐death ceramide species, which was intensified with CNL. Taken together, CNL has the potential to be utilized as an adjuvant therapy to improve outcomes, potentially extending survival, in patients with AML. [ABSTRACT FROM AUTHOR]

Objectives The efficacy of belimumab (BEL) during maintenance therapy in patients with SLE remains unclear in the real-life clinical setting. This study investigated the efficacy and safety of BEL in patients with SLE during maintenance therapy. Methods In this retrospective observational study, maintenance therapy was defined as low-dose glucocorticoid (GC) therapy (prednisolone equivalent dose of ≤0.2 mg/kg/day) in patients with a Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) score <10. Participants comprised patients with SLE on HCQ or MMF [standard-of-care (SoC) group: n  = 103] and those on BEL plus SoC (BEL+SoC group: n  = 100). Selection bias was minimized using propensity score-based inverse probability of treatment weighting (IPTW). GC dose trajectories were modelled using growth mixture modelling (GMM). The primary end point was GC dose at 52 weeks. Results No significant difference was observed in patient characteristics between the two groups after IPTW adjustment. The BEL+SoC group exhibited a significant decrease in GC dose. GC dose at 52 weeks and relapse rate were significantly lower in the BEL+SoC group than in the SoC group. The proportion of patients in one of four groups defined by GMM for which GC dose was tapered to 0 mg within 52 weeks (GC tapering-discontinuation group) was significantly higher in the BEL+SoC group than in the SoC group. In the BEL+SoC group, low SELENA-SLEDAI score and low GC dose at baseline were associated with being GC dose-tapering discontinuation. Conclusion The present study suggests that BEL is suitable for patients with SLE during maintenance therapy. [ABSTRACT FROM AUTHOR]

Background: Worldwide, different strategies have been chosen to face the COVID-19-patient surge, often affecting access to health care for other patients. This observational study aimed to investigate whether the standard of burn care changed globally during the pandemic, and whether country´s income, geographical location, COVID-19-transmission pattern, and levels of specialization of the burn units affected reallocation of resources and access to burn care.Methods: The Burn Care Survey is a questionnaire developed to collect information on the capacity to provide burn care by burn units around the world, before and during the pandemic. The survey was distributed between September and October 2020. McNemar`s test analyzed differences between services provided before and during the pandemic, χ2 or Fisher's exact test differences between groups. Multivariable logistic regression analyzed the independent effect of different factors on keeping the burn units open during the pandemic.Results: The survey was completed by 234 burn units in 43 countries. During the pandemic, presence of burn surgeons did not change (p = 0.06), while that of anesthetists and dedicated nursing staff was reduced (<0.01), and so did the capacity to manage patients in all age groups (p = 0.04). Use of telemedicine was implemented (p < 0.01), collaboration between burn centers was not. Burn units in LMICs and LICs were more likely to be closed, after adjustment for other factors.Conclusions: During the pandemic, most burn units were open, although availability of standard resources diminished worldwide. The use of telemedicine increased, suggesting the implementation of new strategies to manage burns. Low income was independently associated with reduced access to burn care. [ABSTRACT FROM AUTHOR]

The standard of care to which doctors are held in medical practice is based on the peer professional standard in most common law jurisdictions. However, when it comes to the duty to inform the patient of risks in proposed treatment, courts across the common law world have adopted a prudent patient standard to strike a better balance between beneficence and autonomy. Instead of allowing doctors to control the information provided, courts assess what risks are material to a reasonable patient. Singapore is the most recent jurisdiction to follow suit, but the common law development may be short-lived following legislative intervention. This article critically analyses the law on the standard of care in medical negligence, arguing that the legislative reform was based on a misconception of the law. It highlights some of the potential difficulties in implementing the legislative framework. [ABSTRACT FROM AUTHOR]

Cutaneous vasculitis presents a significant challenge to wound care specialists with the potential to result in large areas of dermal necrosis complicated by multisystem pathology leading to poor physiological reserve and treatment options that arrest normal healing. Both surgical and conservative management needs to be flexible as plans can be derailed by the fluctuating course of disease. In this case the application of a synthetic dermal substitute, NovoSorb® Biodegradable Temporizing Matrix (BTM), and ongoing structured assessment using TIMERS and wound standards of care achieved unexpected positive results. [ABSTRACT FROM AUTHOR]

Background: Schizophrenia is a chronic mental disorder associated with substantial morbidity and mortality affecting 0.25-1.6% of adults in the USA. Antipsychotic treatment is the standard of care for schizophrenia, but real-world treatment patterns and associated costs have not been systematically reviewed.Objective: We conducted a systematic review to summarize treatment patterns and associated costs related to oral antipsychotic treatment of patients with schizophrenia in the USA.Data Sources: We searched Medline (via PubMed) and Embase to identify relevant observational studies published from January 1, 2008, to June 1, 2018; costs were converted to 2018 US dollars.Study Eligibility: Observational, real-world studies reporting on patterns of treatment and/or associated costs for adult patients with schizophrenia treated with oral antipsychotics in the USA were included.Results: Eighty-one studies were identified. Frequently prescribed oral second-generation antipsychotics were olanzapine (up to 50.9%), risperidone (up to 40.0%), and quetiapine (up to 30.7%). Suboptimal adherence was common across studies. Antipsychotic switching occurred in about half of patients, while antipsychotic combination therapy occurred in nearly 30%; all were associated with increased medication-related costs. Mean annual direct medical costs differed by treatment, with reported costs of $17,115 to $26,138 for patients treated with olanzapine, $18,395 for risperidone, and $17,656 to $28,101 for quetiapine.Limitations: This systematic review is limited by the variations in definitions of schizophrenia-related clinical terms used between studies and by the inclusion of studies focused on only the US health care system.Conclusions: In the treatment of schizophrenia, suboptimal adherence, antipsychotic switching, and antipsychotic augmentation were all associated with high costs of care in comparison to patients who were adherent and did not require antipsychotic switching or augmentation. These findings illustrate the need for the development of new treatments that address efficacy and adherence challenges of currently available therapies. [ABSTRACT FROM AUTHOR]

Background: Standard-of-care (SoC) medications for the treatment of obstructive hypertrophic cardiomyopathy (oHCM) are recommended as first-line therapy despite the lack of evidence from controlled clinical trials and well known off-target side effects., Objectives: We describe the impact of SoC therapy downtitration and withdrawal in patients already receiving aficamten in FOREST-HCM (Follow-Up, Open-Label, Research Evaluation of Sustained Treatment with Aficamten in Hypertrophic Cardiomyopathy; NCT04848506)., Methods: Patients receiving SoC therapy (beta-blocker, nondihydropyridine calcium-channel blocker, and/or disopyramide) were eligible for protocol-guided SoC downtitration and withdrawal at the discretion of the investigator and after achieving a stable dose of aficamten for ≥4 weeks. Successful SoC withdrawal was defined as at least a 50% dose-reduction in ≥1 medication. Adverse events (AEs) were prospectively evaluated 1 to 2 weeks after any SoC withdrawal., Results: Of 145 patients with oHCM who were followed for at least 24 weeks (mean age 60.5 ± 13.2 years; 44.8% female; 42% NYHA functional class III), 136 (93.8%) were receiving ≥1 SoC therapy; of those, 64 (47%) had an attempt at withdrawal, with 59 (92.2%) successful. Thirty-eight (64.4%) patients completely discontinued ≥1 medication, and 27 (45.8%) achieved aficamten monotherapy with 2 later restarting a SoC medication. There were no significant differences in baseline characteristics on day 1 in FOREST-HCM in those with a SoC-withdrawal vs no-withdrawal attempt. In patients who underwent successful SoC therapy withdrawal, NYHA functional class improved by ≥1 class in 79.2% from baseline, Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score improved to 83.0 ± 15.8 points, and resting and Valsalva left ventricular outflow tract gradient improved to 14.3 ± 10.9 and 32.9 ± 21.4 mm Hg, respectively. N-terminal pro-B-type natriuretic peptide levels improved to a median of 220.0 pg/mL (Q1-Q3: 102.0-554.0.0 pg/mL) and high-sensitivity troponin I improved to a median of 6.0 ng/L (Q1-Q3:3.5-10.7 ng/L). Downtitration and withdrawal of SoC therapy did not impact these results (all P values for change were >0.05), and these changes were similar in patients who did not undergo SoC therapy withdrawal. There were no serious AEs attributed to SoC withdrawal and treatment emergent AEs were similar between groups., Conclusions: In FOREST-HCM, one-half of the patients with oHCM attempted downtitration and withdrawal of SoC medications while receiving aficamten treatment, with infrequent instances of resumption of SoC. Stopping and dose reduction of SoC medications were well tolerated with no adverse consequences in clinical measures of efficacy (Follow-Up, Open-Label, Research Evaluation of Sustained Treatment with Aficamten in Hypertrophic Cardiomyopathy [FOREST-HCM]; NCT04848506)., Competing Interests: Funding Support and Author Disclosures The FOREST-HCM trial is funded by Cytokinetics, Incorporated. Dr Masri has received consulting/advisor fees from Tenaya, Attralus, Cytokinetics, Bristol Myers Squibb, Eidos, Pfizer, Haya, Lexion, BioMarin, Alexion, and Ionis; and has received research grants from Ionis, Pfizer, Cytokinetics, and Attralus. Dr Choudhury has received advisor fees from Cytokinetics. Dr Barriales-Villa has received consulting/advisor fees from MyoKardia/Bristol Myers Squibb. Dr Elliott has received consulting fees from Bristol Myers Squibb, Pfizer, and Cytokinetics; has received speaker fees from Pfizer; and has received an unrestricted grant from Sarepta. Dr Maron has received consulting/advisor fees from Imbria, Edgewise, and Biomarin; and has received steering committee fees for SEQUIOA-HCM from Cytokinetics, Incorporated. Dr Nassif has received research and grant support from AstraZeneca and Cytokinetics; and has received consulting/advisory fees from Vifor and Cytokinetics. Dr Oreziak has received investigator fees from Cytokinetics and MyoKardia/Bristol Myers Squibb. Dr Owens has received consulting/advisor fees from Bristol Myers Squibb; and has received research grants from Bristol Myers Squibb, Cytokinetics, Novartis, and Actelion Pharmaceuticals. Dr Saberi has received consulting fees from Bristol Myers Squibb and Cytokinetics. Dr Tower-Rader has received research grants from Bristol Myers Squibb and Cytokinetics. Dr Rader has received consulting fees/honoraria from Medtronic, Cytokinetics, Bristol Myers Squibb, and Recor. Dr Garcia-Pavia has received Speakers Bureau fees from Bristol Myers Squibb, Pfizer, BridgeBio, Ionis, AstraZeneca, NovoNordisk, Intellia, and Alnylam; has received consulting fees from Bristol Myers Squibb, Cytokinetics, Rocket Pharma, Lexeo Therapeutics, Pfizer, BridgeBio, Daiichi-Sankyo, Neurimmune, Alnylam, AstraZeneca, Novo Nordisk, Attralus, Intellia, Idoven, General Electric, and Alexion; and has received research/educational support to his institution from Pfizer, BridgeBio, NovoNordisk, AstraZeneca, Intellia, and Alnylam. Dr Olivotto has received Speakers Bureau fees from Bristol Myers Squibb, Amicus, and Genzyme; has received consulting/advisor fees from Bristol Myers Squibb, Cytokinetics, Sanofi Genzyme, Amicus, Bayer, Tenaya, Rocket Pharma, and Lexeo; and has received research grant funding from Bristol Myers Squibb, Cytokinetics, Sanofi Genzyme, Amicus, Bayer, Menarini International, Chiesi, and Boston Scientific. Dr Wang has received Speakers Bureau fees from Bristol Myers Squibb; has received consulting/advisor fees from Bristol Myers Squibb and Cytokinetics; and has received research grants from Bristol Myers Squibb, Cytokinetics, and Abbott Vascular. Drs Heitner, Jacoby, Kupfer, Malik, Melloni, Meng, and Wei are employees of and hold stock in Cytokinetics Incorporated. Dr Sherrid has received consulting fees/honoraria from Pfizer Inc; and has served as a consultant for Cytokinetics Inc without payment. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Venous leg ulcers (VLUs) are often large and complicated wounds that, despite combinations of advanced wound care techniques and systemic treatment of underlying vascular issues, take many months to heal and have high rates of recurrence. In this study, we investigated the efficacy of a novel wound care solution-human keratin matrix (HKM)., Method: A case series of VLUs were treated with HKM in conjunction with indicated vascular intervention and standard of care (SoC) procedures. For analysis, these wounds were divided into very large (>200 cm 2 ) and smaller (<35 cm 2 ) wounds., Results: The cohort comprised 16 VLUs (very large=7; smaller=9). Very large VLUs were reduced in size by an average of 71% within 10 weeks, and showed a 50% size reduction within four applications of HKM. Smaller VLUs reduced by 50% in size within the first three weeks of treatment, and 88.9% of these wounds healed completely with an average of 4.5 HKM applications over an average of 6.5 weeks., Conclusion: The results of this series highlight the potential of HKM, in combination with indicated systemic interventions and SoC, as an effective treatment for hard-to-heal (chronic) VLUs, even in very large wounds.

Phyllodes tumors, borderline (BPT) and malignant (MPT), represent a rare group of fibroepithelial breast tumors. Due to their rarity, their treatment remains poorly codified. The precise incidence of these tumors remains unknown. TPMs represent half of breast sarcomas and 1 % of breast tumors. Their treatment at the localized stage is based on surgery, that can be conservative surgery or a mastectomy. The impact of oncoplastic techniques and immediate breast reconstruction is not documented. The excision margins of the BPT and MPT must be free, a wider margin can provide a benefit in local recurrence but in also overall survival in the case of TPM. The optimal width of the excision margin is not known. In the event of positive margins, a second surgery could make up the result of an insufficient first surgery. Chemotherapy does not seem to provide any benefit on recurrence-free survival, but the available data are particularly weak. The data on adjuvant radiotherapy are more important. This allows better local control in the event of breast-conserving surgery. The benefit of post-mastectomy radiotherapy is less documented but can be considered in cases of poor prognostic factors. The management of TPM at the metastatic stage is based on the use of chemotherapy (anthracyclines, Ifosfamide) and local treatment of metastases in cases of oligometastatic disease. Due to the rarity of these tumors, it is essential that their management be discussed within a network of qualified professionals (NETSARC+)., (Copyright © 2024 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Objectives: To conduct an intrapatient comparison of ultra-low-dose computed tomography (ULDCT) and standard-of-care-dose CT (SDCT) of the chest in terms of the diagnostic accuracy of ULDCT and intrareader agreement in patients with post-COVID conditions., Methods: We prospectively included 153 consecutive patients with post-COVID-19 conditions. All participants received an SDCT and an additional ULDCT scan of the chest. SDCTs were performed with standard imaging parameters and ULDCTs at a fixed tube voltage of 100 kVp (with tin filtration), 50 ref. mAs (dose modulation active), and iterative reconstruction algorithm level 5 of 5. All CT scans were separately evaluated by four radiologists for the presence of lung changes and their consistency with post-COVID lung abnormalities. Radiation dose parameters and the sensitivity, specificity, and accuracy of ULDCT were calculated., Results: Of the 153 included patients (mean age 47.4 ± 15.3 years; 48.4% women), 45 (29.4%) showed post-COVID lung abnormalities. In those 45 patients, the most frequently detected CT patterns were ground-glass opacities (100.0%), reticulations (43.5%), and parenchymal bands (37.0%). The accuracy, sensitivity, and specificity of ULDCT compared to SDCT for the detection of post-COVID lung abnormalities were 92.6, 87.2, and 94.9%, respectively. The median total dose length product (DLP) of ULDCTs was less than one-tenth of the radiation dose of our SDCTs (12.6 mGy*cm [9.9; 15.5] vs. 132.1 mGy*cm [103.9; 160.2]; p < 0.001)., Conclusion: ULDCT of the chest offers high accuracy in the detection of post-COVID lung abnormalities compared to an SDCT scan at less than one-tenth the radiation dose, corresponding to only twice the dose of a standard chest radiograph in two views., Clinical Relevance Statement: Ultra-low-dose CT of the chest may provide a favorable, radiation-saving alternative to standard-dose CT in the long-term follow-up of the large patient cohort of post-COVID-19 patients., (© 2024. The Author(s).)

Purpose: To evaluate previously popular technologies in the field of spine surgery, and to better understand their advantages and limitations to the current standards of care. Spine surgery is an ever-evolving field that serves to resolve various spinal pathologies in patients of all ages. While there are established treatments for various conditions, such as lumbar spinal stenosis, idiopathic scoliosis, and degenerative lumbar disease, there is always further research and development in these areas to produce innovative technologies that can lead to better outcomes. As this process progresses, we must remind ourselves of previously tried and tested inventions and their outcomes that have fallen short of becoming a standard to ensure we are able to learn lessons from the past., Methods: A thorough literature review was conducted with the aim of compiling literature of previously utilized technologies in spine surgery. Biomedical databases were utilized to gather relevant articles including PubMed, MEDLINE, and EMBASE. Emphasis was placed on gathering articles with technologies or therapeutics aimed at treating common spinal pathologies including lumbar spinal stenosis (LSS), adolescent idiopathic scoliosis (AIS), and other degenerative lumbar spine diseases. The keywords used were: "failed technologies", "historical technologies", "spine surgery", "spinal stenosis", "adolescent idiopathic scoliosis", and "degenerative lumbar spine disease". A total of 47 articles were gathered after initial review., Results: Different technologies pertaining to spine surgery were identified and critically evaluated. Some of these technologies included X-STOP, Vertiflex, Vertebral Body Stapling, and Dynesys. These technologies were evaluated for their strengths and limitations across their spinal pathology applications. While each type of technology had their benefits, the data tended to be mixed with various limitations across studies., Conclusion: These technologies have been trialed in the field of spine surgery across various spinal pathologies, but still prove of limited efficacy and shortcomings to the current standards of care., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Purpose: Axicabtagene ciloleucel (axi-cel) is an autologous CD19 chimeric antigen receptor (CAR) T-cell therapy that is approved for the treatment of relapsed or refractory large B-cell lymphoma. Little is known about the long-term survivorship after CAR T-cell therapy., Methods: We previously reported the results of 298 patients who were leukapheresed with the intent to receive standard-of-care axi-cel (n = 275 infused) after two or more previous lines of therapy at a median follow-up of 12.9 months. Here, we report extended follow-up of this cohort to a median of 58 months, with a focus on late survivorship events., Results: Among axi-cel-infused patients, progression-free survival at 5 years was 29% and overall survival (OS) at 5 years was 40%. The 5-year lymphoma-specific survival was 53% with infrequent late relapses. However, the 5-year nonrelapse mortality (NRM) was 16.2%, with over half of NRM events occurring beyond 2 years. Patients who were 60 years and older had a lower risk of relapse ( P = .02), but a higher risk of NRM compared with patients younger than 60 years (NRM odds ratio, 4.5 [95% CI, 2.1 to 10.8]; P < .001). Late NRM was mainly due to infections and subsequent malignant neoplasms (SMNs). In total, SMNs occurred in 24 patients (9%), including therapy-related myeloid neoplasms (n = 15), solid tumors (n = 7), and unrelated lymphoid malignancies (n = 2)., Conclusion: In the standard-of-care setting, axi-cel exhibits outcomes consistent with those reported in clinical trials, with sustained, durable responses observed at the 5-year time point. However, late infections and the development of SMN are key survivorship issues that reduce long-term survival after CAR T-cell therapy, particularly in the elderly.

Introduction: Obesity has been associated with increased incidence of cancer thereby impacting the number of patients with obesity who may require radiation therapy (RT) treatment. Previous studies have detailed the impacts of obesity on RT treatment delivery including considerations when positioning, imaging, and communicating with patients. However, there is limited literature regarding best clinical practices used by Canadian RT departments when treating patients with obesity. This study aimed to answer the following question: How can the current standards of care (SOC) used by Alberta RT departments be improved to ensure safe and quality care of patients with obesity?, Methods: Semi-structured interviews were conducted with 19 practitioners including three RT managers, two medical physicists, two clinical educators, two radiation oncologists, a senior practice lead, and nine radiation therapists from five cancer centers across Alberta. Interviews were transcribed and analyzed independently by two researchers and used to inform recommendations for improvement to existing care practices., Results: Four themes emerged as unique considerations for patients with obesity undergoing RT, which included technical factors, interpersonal interactions, patient care factors, and education and training. Recommendations to improve the current SOC in Alberta RT departments included the need for longer appointment times, sufficient staff, accessible mobility equipment, and additional education and training for HCPs tailored towards patients with obesity., Conclusion: SOC in Alberta could be improved for patients with obesity with modified appointment time, increased staff and resources, and more in depth and tailored education. Implementation of these considerations and recommendations for improvement to the current SOC used by Alberta RT departments has the potential to ensure safe and quality care of patients with obesity., (Copyright © 2024. Published by Elsevier Inc.)

Background: Multidisciplinary Shock Teams have improved clinical outcomes for cardiogenic shock, but their implementation costs have not been studied. This study's objective was to compare costs between patients treated with and without a Shock Team and determine if the team's implementation is cost-effective compared with standard of care., Methods: We examined patients with refractory cardiogenic shock treated with or without a Shock Team at a tertiary academic hospital from 2009 to 2018. Real-world hospital data were used to compare costs and outcomes, including survival at discharge, 1-year survival, and quality-adjusted life years gained at 1 year. Incremental cost-effectiveness ratios were calculated over a 1-year time horizon, with parameter uncertainty evaluated through probabilistic sensitivity analysis using 1000 second-order Monte Carlo simulations., Results: The study involved 244 patients, with 123 treated by the Shock Team and 121 receiving standard of care. Patients were predominantly male (77.5%), with a mean age of 58 (18-92) years. The Shock Team approach improved survival rates at hospital discharge and 1-year follow-up (61.0% versus 47.9%; P =0.04 and 55.0% versus 40.5%; P =0.03, respectively). The incremental cost-effectiveness ratio for increases in survival probability at discharge for the multidisciplinary Shock Team compared with standard of care was $102 088. The incremental cost-effectiveness ratio for increases in survival probability at 1-year was estimated at $96 152 and at $127 862 per 1 quality-adjusted life year gained. Probabilistic sensitivity analysis estimates showed that the Shock Team was cost-effective in the majority of simulations using a willingness-to-pay threshold of $150 000, while it was also dominant in almost one-third of the simulations., Conclusions: The Shock Team approach for treating refractory cardiogenic shock may be a cost-effective alternative to traditional standard of care. These findings can help prioritize the implementation of Shock Team initiatives to further improve cardiogenic shock outcomes.

The Centers for Disease Control and Prevention (CDC) guidelines for hepatitis C virus (HCV) testing, although effective, may miss crucial diagnostic opportunities. The goal of this study was to assess the utility of an antibody (Ab) and antigen (Ag) combination immunoassay as an alternative to traditional HCV screening. Remnant specimens from 1,341 patients with concurrent third-generation serologic (Roche anti-HCV-II) and nucleic acid amplification testing (NAAT) were assessed using the HCV Duo Ab/Ag immunoassay (Roche). Patient demographics, risk factors, and standard of care (SOC) laboratory results from the medical records were recorded. Overall, 99.0% (197/199) of the HCV Duo Ab+/Ag+specimens accurately identified active infections as confirmed by NAAT, and 99.9% (670/671) Ab-/Ag- samples corresponded to those without HCV infections. Individually, the HCV Duo Ab component demonstrated a 95.6% positive percent agreement (PPA) (95% CI = 93.8-96.9) and 99.1% negative percent agreement (NPA) (98.8-99.6) compared with SOC anti-HCV II Ab assay. The HCV Duo Ag had a 73.5% PPA (67.9-78.4) and 99.8% NPA (99.3-100) with NAAT. Among RNA+ specimens, 73.4% (197/267) were HCV Duo Ag+, and 265/267 (99.3%) were successfully detected on the HCV Duo Ab component. Notably, 5/7 (71.4%) Ab-/RNA +specimens were detected by HCV Duo, which would have been missed by traditional algorithmic testing. Fourth generation HCV Duo Ab/Ag assay demonstrated comparable performance to SOC testing and shortens the diagnostic window but does not eliminate the need for NAAT in all patients. Ab/Ag testing identified several Ab-/RNA+ cases, a subgroup often undiagnosed by current algorithmic testing, demonstrating promise for improved diagnostic efficiency and accuracy in HCV detection.IMPORTANCEThis study highlights the potential of a combined hepatitis C virus (HCV) Duo antibody (Ab) and antigen (Ag) immunoassay to improve early detection of HCV infections. Traditional Ab-only screening methods recommended by the Centers for Disease Control and Prevention may miss early-stage infections. The HCV Duo assay showed high accuracy, detecting nearly all active infections confirmed by nucleic acid amplification testing. Dual detection of HCV Ab and Ag shortens the diagnostic window, enabling intervention and treatment in a single visit, which is crucial for improving patient outcomes and reducing HCV transmission, especially in areas with limited access to confirmatory molecular testing., Competing Interests: T.I.B. has no conflict of interest. N.W.A. has served on scientific advisory boards for Roche Diagnostics and Diasorin Molecular. C.W.F. has served on scientific advisory boards for Werfen, Abbott Laboratories, Roche Diagnostics, and Cytovale and received research funding from Beckman Coulter, Abbott Laboratories, Roche Diagnostics, Cepheid, Siemens Healthineers, and Biomerieux.

Objective: Lumbar pedicle screw placement surgery involves various assistive technologies, including fluoroscopic, stereotactic, or robotic navigation and intraoperative neuromonitoring (IONM). We aimed to discern neurosurgeons' preferences for screw placement techniques and IONM utility, while also considering the influence of experience., Methods: A survey was distributed to members of the Congress of Neurological Surgeons using REDCap software, collecting demographic data and querying preferred techniques for screw placement and IONM modalities. Opinions on IONM use during stereotactic or robotic navigation were also obtained. Responses were analyzed using Pearson's Chi Square and ANOVA tests via R software., Results: Of 188 responses, 35.5% (n=67) reported 1-10 years of experience and 64.5% (n=121) reported ≥11 years. Less experienced neurosurgeons utilized stereotactic navigation more than those with greater experience (p < 0.001). Seasoned neurosurgeons utilized fluoroscopic guidance more often (p = 0.038). Less experienced neurosurgeons employed 1.69 (±0.11) techniques for their fixation surgeries compared to 1.50 (±0.0.8) for more experienced neurosurgeons. Robotic navigation utilization was low and comparable between the groups. Surgeons employing multiple techniques utilized t-EMG the most (62.1%, p = 0.024). No strong opinions emerged on the necessity of multi-modality IONM with robotic or stereotactic navigation., Conclusions: This national survey shows that stereotactic navigation is the predominant technique for pedicle screw placement among less experienced neurosurgeons, with seasoned neurosurgeons leaning towards fluoroscopic guidance. Robotic guidance was the least utilized technique with no observed difference based on experience. Neurosurgeons employing multiple techniques use IONM the most, compared with surgeons who only use stereotactic navigation and/or robotic guidance., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Pharmacogenomic (PGx) factors significantly influence how patients respond to antipsychotic medications This systematic review was performed to synthesize the clinical utility of PGx-assisted treatment versus standard of care in schizophrenia., Methods: PubMed, Embase, and Cochrane CENTRAL databases were searched for randomized controlled trials (RCTs) from inception till June 2024 that had compared the clinical utility of PGx-assisted intervention as compared to the standard of care in schizophrenia. The primary outcome was safety, and the secondary outcomes were efficacy and medication adherence. Pooled standardized mean differences (SMD) along with a 95% confidence interval (CI) were calculated (random-effects model) wherever feasible., Results: A total of 18,821 studies were screened, and five were included for review. All the RCTs had a high risk of bias. Four studies included the commonly used antipsychotics. Three studies reported negative outcomes (safety, efficacy, and medication adherence) and two reported positive outcomes (safety) using different scales. In the meta-analysis, there were significant differences in the total Udvalg for Kliniske Undersogelser Side-Effect Rating scale score [SMD 0.95 (95% CI: 0.76-1.13), p < 0.001); I 2  = 0%] and the total Positive and Negative Syndrome Scale score [SMD 10.65 (95% CI: 2.37-18.93), p = 0.01); I 2  = 100%] between the PGx-assisted treatment and standard of care arms. However, the results were inconsistent, and the certainty of evidence (GRADE criteria) was very low., Conclusion: Current evidence on the clinical utility of PGx-assisted treatment in schizophrenia is limited and inconsistent and further evidence is required in this regard., (© 2024. The Author(s).)

Background: People with schizophrenia often experience long-term psychosocial disabilities and frequent relapse. Family plays a key role in caring for ill relatives, which in turn probably contributes to high levels of distress and burdens for the family. Family-based interventions have been developed and applied to family members and their relatives with schizophrenia to improve their outcomes. This is an update of a Cochrane review that was last updated in 2011, which has been split into this review, one on group- versus individual-based family interventions and one on family-based cognitive versus behavioural management interventions., Objectives: To assess the effects of family-based interventions for people with schizophrenia or schizophrenia-like disorders and their families compared with standard care., Search Methods: We searched the following electronic databases from inception until April 2023: CENTRAL, Medline, Embase, PsycInfo, CINAHL, WHO International Clinical Trials Registry Platform (ICTRP), Clinicaltrials.gov, SinoMed, China Network Knowledge Infrastructure (CNKI), Wanfang, and Chinese Scientific Journals Database (VIP). We also searched the reference lists of included studies and accessible reviews for additional references., Selection Criteria: We included randomised controlled trials (RCTs) that compared the effects of family-based interventions for people with schizophrenia or schizophrenia-like disorders and their families and reported at least one patient's and one family member's outcomes. In this update, we only investigated standard care as the comparator., Data Collection and Analysis: We used standard Cochrane methods. The review authors independently screened studies, extracted data, and assessed risk of bias for each study using the Cochrane risk of bias tool for RCTs. We pooled data and estimated effects with the mean difference (MD), standardised mean difference (SMD), or risk ratio (RR) with 95% confidence interval (CI). We judged the certainty of evidence using GRADEpro GDT. We divided the outcomes into short-term (≤ 1 month postintervention), medium-term (> 1 to 6 months postintervention), and long-term follow-up (> 6 months postintervention), if available., Main Results: We identified 26 RCTs in this review, with 1985 people with schizophrenia or schizophrenia-like disorders, and 2056 family members. Most family-based interventions were conducted on a weekly or biweekly basis, with duration ranging from five weeks to two years. We had substantial concerns regarding the methodological quality of the included studies given that we judged all studies at high risk of performance bias and several studies at high risk of detection, attrition or reporting bias. Low-certainty evidence indicated that family-based interventions may reduce patients' relapse at one month or less postintervention (RR 0.66, 95% CI 0.49 to 0.89; 4 RCTs, 229 participants). We downgraded the evidence by two levels due to imprecision (small number of participants) and high risk of performance, detection and attrition bias. Compared to standard care, family-based interventions probably reduce caregiver burden at one month or less postintervention (MD -5.84, 95% CI -6.77 to -4.92; 8 RCTs, 563 participants; moderate-certainty evidence) and may result in more family members shifting from high to low expressed emotion (RR 3.90, 95% CI 1.11 to 13.71; 2 RCTs, 72 participants; low-certainty evidence). Family interventions may result in little to no difference in patients' death (RR 0.48, 95% CI 0.18 to 1.32; 6 RCTs, 304 participants; low-certainty evidence) and hospital admission (≤ 1 month postintervention; RR 0.81, 95% CI 0.51 to 1.29; 2 RCTs, 153 participants; low-certainty evidence) in comparison with standard care. Due to the heterogeneous measures and various follow-up periods, we were unable to provide pooled effect estimates for patients' compliance with medication and quality of life. We were very uncertain whether family interventions resulted in enhanced compliance with medication and improved quality of life for patients. We downgraded the evidence to very low certainty due to high risk of bias across studies, inconsistency (different directions of effects across studies), and imprecision (small number of participants or CIs of most studies including the possibility of no effect)., Authors' Conclusions: This review synthesised the latest evidence on family interventions versus standard care for people with schizophrenia or schizophrenia-like disorders and their families. This review suggests that family interventions might improve patients' outcomes (e.g. relapse) and families' outcomes (e.g. caregiver burden and expressed emotion), with little to no difference in patients' hospital admission and adverse effects in terms of death. However, evidence on patients' compliance with medication and quality of life was very uncertain. Overall, the evidence was of moderate to very low certainty. Future large and well-designed RCTs are needed to provide more reliable evaluation of effects of family interventions in people with schizophrenia or schizophrenia-like disorders and their families., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Objective: To present a list of key points for good Temporomandibular Disorders (TMDs) clinical practice on behalf of the International Network for Orofacial Pain and Related Disorders Methodology (INfORM) group of the International Association for Dental, Oral and Craniofacial Research (IADR)., Methods: An open working group discussion was held at the IADR General Session in New Orleans (March 2024), where members of the INfORM group finalized the proposal of a list of 10 key points., Results: The key points covered knowledge on the etiology, diagnosis, and treatment. They represent a summary of the current standard of care for management of TMD patients. They are in line with the current need to assist general dental practitioners advance their understanding and prevent inappropriate treatment., Conclusions: The key points can be viewed as a guiding template for other national and international associations to prepare guidelines and recommendations on management of TMDs adapted to the different cultural, social, educational, and healthcare requirements.

Diabetic foot ulcers (DFUs) are a severe complication for diabetic patients, significantly impacting patient quality of life and healthcare system efficiency. Traditional standard of care (SOC) treatments are inadequate for many patients, necessitating the use of advanced wound care products, such as human placental membranes. We studied a real-world population of large, hard-to-heal and complicated wounds, otherwise under-studied in the wound care literature. To this end, we conducted a retrospective cohort analysis to compare the effectiveness of a human placental amnion/chorion membrane product using retention-based processing (RE-AC) and SOC in managing chronic DFUs. During the study period of September 2021 through April 2024, we collected retrospective observational data from electronic health records of 21 patients treated with RE-AC at three outpatient wound care centres. Additionally, 21 control SOC patients were matched from a wound registry using Coarsened Exact Matching. Patients were categorized into two cohorts based on whether they received RE-AC or SOC. Key metrics included wound size progression and wound closure. The analysis employed Bayesian regression and Hurdle Gamma Analysis of Covariance models. Despite their rather large size (average of 13.8 cm 2 ), our results indicated that RE-AC achieved almost a 10% higher expected wound closure rate compared to SOC at 12 weeks (8.53% [credible interval: 5.60%-10.7%]). Further, for wounds that did not close, RE-AC resulted in a 93.6% (credible interval: 147.7%-41.6) improvement in expected Percent Area Reduction over the SOC group at 12 weeks. We noted that on average, SOC wounds stalled or grew larger. In terms of a risk ratio comparing the study group with SOC, we found a 52% benefit in the RE-AC group (RR = 1.52). The findings suggest that even with larger DFUs, R-AC is superior to SOC for wound closure and expected Percent Area Reduction by 12 weeks. This benefit likely leads to reduced treatment costs, optimized resource utilization and improved outcomes in the DFU patient population; ultimately resulting in improved patient care., (© 2024 The Author(s). International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Background: Orthopedic deep surgical incisions require the approximation of 1 or multiple tissue layers. This prospective randomized controlled study aimed to assess the usefulness and effectiveness of a barbed suture technique (Stratafix symmetric PDS plus) versus the conventional interrupted knotted suture technique for deep tissue closure in orthopedic surgery by comparing deep fascia suture time, relative cost, and wound-related complications., Methods: A total of 254 patients with deep surgical incisions who underwent orthopedic surgery between October 1, 2020, and June 30, 2021, were recruited. Their general characteristics (age, sex, weight, height, body mass index, American Society of Anesthesiologists physical status score, total operation time, and length of deep incision) and factors related to deep incision wounds (suture type and number, wound closure time, and operation site outcomes) were collected., Results: The general characteristics did not differ between the Stratafix and conventional groups. There were no between-group differences observed in total operation time or total anesthesia time. The wound suture times differed significantly. In the conventional group, the suture time per unit length was lower in the group with the length of deep incision under 20 cm but did not differ significantly for each wound size. In the Stratafix group, the suture time per unit length was lower in the group under 15 cm, with the shortest time observed for 10-14.9 cm, followed by 5.0-9.9 cm and the group under 5 cm. The conventional group developed 4 cases of superficial wound infection or surgical wound necrosis. One case of protruded suture tap occurred in the Stratafix group., Conclusions: The average suture time per unit length increased for lengths under 5 cm as barbed sutures required more time from the start of the first suture to finish of the last suture. There was no significant benefit for very short suture length. One barbed suture material allows a suture of approximately 10-12 cm; sutures beyond that require more time because the surgeon has to start again. The Stratafix group used less suture material than the conventional group., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported., (Copyright © 2024 by The Korean Orthopaedic Association.)

Acute immune thrombotic thrombocytopenic purpura (iTTP) is a medical emergency. In the setting of any thrombotic microangiopathy (TMA), blood should be drawn to measure ADAMTS13 activity and inhibitor levels, and an assessment should be made of TTP risk before receiving ADAMTS13 results. This can include the use of PLASMIC and French scores. Plasma exchange (PE) is then initiated. Upon confirmation of iTTP, with ADAMTS13 less than 10% in the presence of an inhibitor, interventions targeting all facets of iTTP pathophysiology should be instituted: replenishing ADAMTS13 via continued PE; suppressing anti-ADAMTS13 autoantibodies with glucocorticoids and rituximab; and inhibiting the thrombotic process-uncontrolled formation of platelet/Von Willebrand factor (VWF) microthrombi-with caplacizumab. The latter, an addition to existing standards of care, is based on International Society on Thrombosis and Haemostasis guidelines and emphasizes tracking of ADAMTS13 activity. In HERCULES, a pivotal randomized controlled trial, caplacizumab use resulted in fewer recurrent iTTP episodes, decreased PE, and shortened hospital stay. In settings of high suspicion for iTTP, clinicians should consider the administration of caplacizumab before receiving ADAMTS13 results because the greatest benefits of caplacizumab accrued starting it within 3 days of TMA recognition. In HERCULES, serious bleeding events occurred among 11% of those in the caplacizumab group vs 1% in the placebo group, but all resolved, most without intervention. iTTP survivors receiving PE and immunosuppression alone are at a heightened risk for stroke, other cardiovascular disorders, neurocognitive impairment, and kidney disease. Whether rapid prevention of VWF multimer/platelet formation with caplacizumab can suppress such long-term sequelae, and whether caplacizumab can replace PE in initial therapy, are under investigation.

Competing Interests: Conflict of Interest All authors declare no conflicts of interest related to the matter of this statement.

While surgery, when possible, remains the mainstay of pediatric low-grade glioma (pLGG) management, adjuvant therapy has significantly evolved over time. Radiation therapy was commonly used in the late 1990s for tumors that could not be resected or recurred. This resulted in significant late morbidity in this population and mortality related to secondary malignancies and chronic health conditions. Chemotherapy became the mainstay of adjuvant therapy but children still experienced late morbidity secondary to exposure to multiple lines of treatment over time. Targeted therapies emerged after the identification of frequent genetic alterations in the mitogen activated protein kinase (MAPK) pathway including KIAA1549-BRAF fusions and BRAF-V600 mutations and the near universal upregulation of the MAPK pathway in these tumors. Both BRAF and MEK inhibitors have shown efficacy in the treatment of pLGG and have led to prolonged stability in some cases. Multiple phase III clinical trials are now comparing targeted therapy to standard-of-care chemotherapy regimens setting the stage for targeted therapy to replace chemotherapy as the first-line treatment in some cases. Targeted therapy, however, is not without its challenges. There are clear examples of resistance and mechanisms of resistance have not been fully elucidated. There is also no clear duration for these therapies and rebound growth is a well-known phenomenon especially in BRAF-V600 mutant tumors. Targeted therapies are also fairly recent developments and long-term toxicities and functional outcomes are still being monitored. Very young and adolescent/young adult LGGs also carry molecular features that may not be addressed by inhibition of the MAPK pathway. Adjuvant therapy for pLGG has evolved from radiation for all unresectable or residual tumors to molecularly driven targeted therapies with improved quality of life, late effects, and less off-target toxicities. While there is still much to learn in regard to newer targeted therapies for pLGG, the era of targeted therapies for pediatric LGG is upon us., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Outcomes related to chronic intestinal failure (CIF) vary significantly within and between countries. While there are extensive European Society of Clinical Nutrition and Metabolism (ESPEN) guidelines on the delivery of optimal care in CIF, there are no international consensus recommendations on the structure or resources required, nor on the process and appropriate outcome measures for delivering such quality care in CIF., Aim: The aim of this position paper is therefore to devise ESPEN-endorsed, internationally agreed quality of care standards, covering the resources, systems and standards that centres should aim for in order to deliver optimal CIF care., Methods: Members of the Home Artificial Nutrition-CIF Special Interest Group of ESPEN proposed an initial set of quality-of-care standards which was submitted to voting amongst clinicians from international CIF centres using a modified Delphi process, with participants rating each proposed statement as 'essential', 'recommended' or 'not required'. Any statement receiving 80% of more 'not required' responses was excluded., Results: All 30 proposed standards relating to the structure, 18 relating to the process and 16 to the outcome measures of CIF care were deemed to be essential or recommended in more than 80% of respondents., Conclusion: This is the first paper to determine and describe internationally-agreed quality of care standards in CIF, which are now aimed at forming the basis for all CIF teams to develop and monitor their service, while also informing policymakers and payers on the infrastructure required for the optimal approach to multi-disciplinary team CIF care delivery. The recording of standardised outcomes should also allow internal and external benchmarking of care delivery within and between CIF centres., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Standardized care is crucial in health care for ensuring consistent, safe, high-quality, efficient, and evidence-based practices. Care pathways that standardize procedures promote adherence to best practices, reduce variability in treatment, and encourage collaboration among health care teams. This approach ultimately improves patient outcomes, enhances safety, and boosts the overall effectiveness of health care services. However, despite these benefits being widespread across most of the U.S. health care system, wound care stands out as an area where standards can vary significantly. The inconsistency in wound care standards in the United States can be traced to several factors. These include limited structured clinical wound care education, the discretion of health care providers in different business environments, differences in wound care settings, varying access to advanced treatments and technology, patient demographics and socioeconomic status, as well as differences in state laws and regional or institutional practices. Addressing these disparities requires a comprehensive approach that considers the complex interplay of the abovementioned factors. Active measures are needed to improve access, equity, and the quality of wound care services for all patients, regardless of where they live, their socioeconomic status, their health care coverage, or the business interests of providers and their institutions as well as of vendors marketing wound care products inconsistent with evidence-based practice. By understanding and actively addressing these factors, we can work toward achieving more standardized, evidence-based, and patient-centered practices in wound care across the nation.

Since 1980's, the established/standard treatment of acute myeloid leukemia (AML) is cytarabine infusion with anthracycline (7 + 3 regimen). We compared the 7 + 3 regimen in older secondary/high-risk AML patients from a clinical trial with a matched population from the Swedish AML Registry treated with an increased cytarabine dose in induction and consolidation as recommended in the Swedish National Guidelines since 2005. After successful propensity score matching, 104 patients per group were included. The primary outcome was overall survival (OS), and standard dosed patients had a median OS of 6.4 versus 10.7 months with increased dose intensity (hazard ratio: 0.69, p  = 0.012), with 5-year OS of 8.7% and 18.1%, and remission rates of 36% and 60%, respectively ( p  < 0.001). Median OS after allogeneic hematopoietic cell transplantation (in 27.9% per group) was 10.4 and 20.7 months, respectively. We conclude that the more intensive cytarabine schedule seems to provide improved outcomes inthe investigated AML patient group.

Objectives: Adherence to the American Diabetes Association (ADA) Standards of Medical Care is low. This study aimed to assist pharmacists in identifying patients for diabetes control interventions using unsupervised machine learning., Methods: This study analyzed the 2021 Medical Expenditure Panel Survey and used a k-mode cluster analysis. Patient features analyzed were adherence to a select set of preventive measures from the ADA Standards of Medical Care (HbA1c test, foot examination, blood cholesterol test, dilated eye examination, and influenza vaccination) and some patient characteristics (age, gender, health insurance, insulin use, and diabetes-related complications)., Results: The study included 1,219 patients with self-reported diabetes, and the adherence rate to the ADA standards was 33.72%. Five distinct clusters emerged: (A) moderate-complexity, privately insured male; (B) moderate-complexity, publicly insured female; (C) low-complexity, privately insured female; (D) high-complexity, publicly insured female; (E) moderate-complexity, publicly insured male. Groups B, C, and E exhibited nonadherence., Conclusions: Pharmacists can target publicly insured elderly (Groups B and E) and privately insured middle-aged females (Group C) for interventions. For instance, pharmacists may help patients in Groups B and E locate existing resources in their insurance program and remind those in Group C of the importance of adequate diabetes care.

Competing Interests: VH declares grants or contracts to their institution from Merck, Amgen, Roche, Celgene, Boehringer-Ingelheim, Sirtex, Shire, and Servier; consulting fees from Merck, Roche, AstraZeneca, GSK, Celgene, Amgen, Servier, Novartis, Pierre-Fabre, Halozyme, MSD, BMS, Janssen, Terumo, Sirtex, Oncosil, Nordic Pharma, and Boehringer-Ingelheim; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Merck, AstraZeneca, GSK, Amgen, Roche, Sanofi, Servier, Pfizer, Pierre-Fabre, BMS, MSD, Novartis, Boehringer-Ingelheim, Celgene, Sirtex, and Seagen; support for attending meetings or travel from Merck, Nordic Pharma, AstraZeneca, GSK, Amgen, and MSD; and has participated on a data safety monitoring board or advisory board for ICON. SS declares grants or contracts to their institution from Merck, Pierre-Fabre, and Roche; consulting fees from Amgen, AstraZeneca, Bayer, Lilly, Merck, MSD, Pierre-Fabre, Roche, Sanofi, Servier, Taiho, CV6, and Isofol; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Amgen, AstraZeneca, Bayer, Lilly, Merck, MSD, Pierre-Fabre, Roche, Sanofi, Servier, and Taiho; support for attending meetings or travel from Amgen, AstraZeneca, Bayer, Lilly, Merck, MSD, Pierre-Fabre, Roche, Sanofi, Servier, and Taiho; and has participated on a data safety monitoring board or advisory board for CV6 and Isofol.