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Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cause of cancer worldwide according to GLOBOCAN estimates from 2022. Current therapy options for recurrent or metastatic disease are limited to conventional cytotoxic chemotherapy and immunotherapy, with few targeted therapy options readily available. Recent single-cell transcriptomic analyses identified TGF-β signaling as an important mediator of functional interplays between cancer-associated fibroblasts and a subset of mesenchymal cancer cells. This signaling was shown to drive invasiveness, treatment resistance, and immune evasion. These data provide renewed interest in the TGF-β pathway as an alternative therapeutic target, prompting a critical review of previous clinical data which suggest a lack of benefit from TGF-β inhibitors. While preclinical data have demonstrated the great anti-tumorigenic potential of TGF-β inhibitors, the underwhelming results of ongoing and completed clinical trials highlight the difficulty actualizing these benefits into clinical practice. This topical review will discuss the relevant preclinical and clinical findings for TGF-β inhibitors in HNSCC and will explore the potential role of patient stratification in the development of this therapeutic strategy.

Visual Abstract: of key results. INR, international normalized ratio; TTR, time in therapeutic range; PTR, percentage of tests in range; HRAE, hemocompatibility-related adverse event; FFUV, first follow-up visit; GIB, gastrointestinal bleeding; HR, hazard ratio.http://links.lww.com/ASAIO/A961., Competing Interests: Disclosure: T.S. consultant and advisor (Medtronic Inc., Abbott Inc., and CorWave), and research grants (Medtronic Inc., Abbott Inc., and CorWave). H.S. advisor (Medtronic Inc.), and research grants (Medtronic Inc). D.Z. proctor, advisor, and speaker (Medtronic Inc., Abbott Inc., Berlin Heart, Edwards, Abiomed), and research and travel grants (Medtronic Inc. and Abbott Inc). All the other authors have no conflicts of interest to report., (Copyright © ASAIO 2023.)

Background: While the pledget suture technique has been the standard for surgical aortic. valve replacement (AVR), discussion continues regarding the possibility of the nonpledget suture technique to produce superior structural and hemodynamic parameters. This study aims to assess the effectiveness of the figure-of-eight suture technique in AVR, as determined by the incidence of prosthesis-patient mismatch (PPM)., Methods: We reviewed records of patients (N = 629) who underwent a surgical AVR procedure between January 2011 and July 2018 at a single institution. Indexed effective orifice area values and PPM incidence were calculated from implanted valve size and patient body surface area. Incidence of none, moderate, and severe PPM was compared across AVR suture techniques., Results: A total of 570 pledget and 59 figure-of-eight patients were compared for incidence of PPM. Patients who received AVR with the pledget suture technique had significantly lower echocardiographic measurements of baseline ejection fraction than patients who had received AVR with the figure-of-eight suture technique (p = 0.003). Patients who received the figure-of eight suture had a 14% decrease in moderate PPM compared to patients who received the pledget suture (p = 0.022). Patients who received the figure-of-eight suture also had a significantly higher rate of no PPM (p = 0.044)., Conclusions: The use of the figure-of-eight suture technique in AVR can reduce the incidence of moderate PPM. While the pledget suture is the standard technique in AVR, the figure-of-eight suture technique may offer better structural and hemodynamic outcomes, especially for patients with a smaller aortic annulus., (© 2023. The Author(s).)

Background: Patients with concomitant anemia and congestive heart failure have poor outcomes. The prevalence and clinical risk of anemia in patients receiving durable left ventricular assist devices (LVAD) remain unknown., Methods: We retrospectively analyzed patients who underwent LVAD implantation between 2014 and 2018. The association between hemoglobin level at the time of index discharge and the one-year composite endpoint of heart failure readmissions or hemocompatibility-related adverse events was investigated., Results: A total of 168 patients (57 [48, 66] years old, 123 males) were included and stratified into a classification of anemia (hemoglobin <9.7 g/dl, N = 99) or non-anemia (N = 69). The anemia group had a higher one-year incidence of the composite endpoint (56% vs 36%, p = .013) with an adjusted hazard ratio of 1.83 (95% confidence interval 1.08-2.82). Patients with anemia also experienced suboptimal bi-ventricular unloading., Conclusions: Anemia was prevalent in LVAD patients and associated with a greater risk of heart failure and hemocompatibility-related adverse events. The optimal threshold for therapeutic intervention in response to post-LVAD anemia needs further investigation., (© 2022 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Background: Both hypo- and hyperkalemia are associated with adverse events in heart failure patients. Their effects on patients with left ventricular assist devices (LVADs) remains unknown. Methods and Results: The cohort included consecutive patients undergoing LVAD implantation between 2014 and 2018. In all, 170 patients (median age 56 years; 117 males) were stratified according to serum potassium levels 1 month after implantation into 3 groups: hypokalemia (<3.5 mEq/L; n=15), normokalemia (n=146), and hyperkalemia (>5.0 mEq/L; n=9). Compared with the normokalemia group, the adjusted hazard ratios for 1-year mortality were 0.91 (95% confidence interval [CI] 0.21-3.92) for hypokalemia and 4.14 (95% CI 1.47-11.65) for hyperkalemia. In the hyperkalemia group, the prevalence of renin-angiotensin-aldosterone system inhibitors decreased and serum potassium levels normalized following the first month. Conclusions: Hyperkalemia was associated with increased mortality during LVAD support. Management of serum potassium needs further investigation., Competing Interests: T.I. has received grant support from JSPS KAKENHI (JP20K17143). V.J. is a consultant for Abbott Inc., Medtronic Inc., and Reliant Heart Inc. The remaining authors have no conflicts of interest to disclose., (Copyright © 2021, THE JAPANESE CIRCULATION SOCIETY.)

Worsening systemic congestion is often the central trigger of hospitalization in patients with heart failure. However, accurate assessment of congestion is challenging. The prognostic impact of systemic congestion following durable continuous-flow left ventricular assist device (LVAD) implantation remains unknown. Consecutive patients who received durable continuous-flow LVAD implantation between January 2014 and June 2017 and were followed for 1 year were included. The association of preoperative plasma volume status, which was calculated using patients' body weight and hematocrit and expressed as a deviation from ideal plasma volume, with 1-year mortality following LVAD implantation was investigated. In total, 186 patients (median 57 years and 138 males) were included. Baseline plasma volume status was -30.1% (-37.1%, -19.4%) on median. Eighty-eight patients (47%) had higher plasma volume status (>-29.8%), and their 1-year survival was significantly lower than those without (67% vs. 87%, P = .001). High plasma volume status was an independent predictor of 1-year death with an adjusted hazard ratio of 4.52 (95% confidence interval 1.52-13.5). Baseline systemic congestion, as defined by the high plasma volume status, was associated with higher mortality following durable continuous-flow LVAD implantation. The implication of improving preoperative plasma volume remains an area of needed investigation., (© 2020 International Center for Artificial Organs and Transplantation and Wiley Periodicals LLC.)

Background: The negative impact of baseline hypoalbuminemia on clinical outcome following left ventricular assist device (LVAD) implantation is well known. However, the implications of perioperative change in serum albumin levels on post-LVAD outcomes remain uninvestigated., Methods: Among consecutive patients with baseline serum albumin <3.5 g/dl who received durable LVAD implantation between April 2014 and August 2017 and were followed for 1 year, the impact of perioperative change in serum albumin level from baseline to 3 months post-LVAD on the incidence of adverse events was investigated., Results: Sixty-eight patients (median 60 years and 69% male) were included. Serum albumin change was an independent predictor of the occurrence of adverse events with an adjusted hazard ratio of 0.32 (95% confidence interval, 0.13-0.78) and a cutoff change of 0.7 g/dl. Those with albumin increase >0.7 g/dl had higher 1-year freedom from adverse events (45% vs. 14%, p = .008), dominantly due to lower incidence of death or sepsis compared with those without (p < .05 for both)., Conclusion: Among those with baseline hypoalbuminemia, a considerable perioperative increase in serum albumin levels following LVAD implantation was associated with lower mortality and morbidity. The implication of aggressive nutrition intervention on LVAD patients is the next concern., (© 2020 Wiley Periodicals LLC.)

The use of opioids during left ventricular assist device (LVAD) support is increasing, but the implication remains unknown. We investigated the association between the use of opioid and morbidities during LVAD supports. We retrospectively reviewed the clinical data of patients who received LVAD between 2014 and 2017, which were stratified by the use of opioid at post-LVAD 3 months. Among 136 patients, 77 (57%) were in the opioid group. Hemoglobin and albumin were lower, and C-reactive protein was higher at baseline and 3 months later in the opioid group (P < 0.05 for all). The opioid group displayed worse hemodynamics, with higher pulmonary capillary wedge pressure and central venous pressure (P < 0.05 for both). Furthermore, the opioid group had higher incidences of gastrointestinal bleeding (31% versus 17%, P = 0.043) and sepsis (30% versus 13%, P = 0.036) during the 1 year observational period, whereas survivals were not stratified by the use of opioid (83% versus 90%, P = 0.27). Opioid use was associated with morbidities accompanied by poor hemodynamics during LVAD supports. The detailed causality of opioid use on morbidities remains a future concern.