Predictors, prognosis and costs of prolonged intensive care unit stay after surgery for type A aortic dissection.

BACKGROUND: The outcomes after prolonged treatment in the intensive care unit (ICU) after surgery for Stanford type A aortic dissection (TAAD) have not been previously investigated. METHODS: This analysis included 3538 patients from a multicenter study who underwent surgery for acute TAAD and were admitted to the cardiac surgical ICU. RESULTS: The mean length of stay in the cardiac surgical ICU was 9.9±9.5 days. The mean overall costs of treatment in the cardiac surgical ICU 24086±32084 €. In-hospital mortality was 14.8% and 5-year mortality was 30.5%. Adjusted analyses showed that prolonged ICU stay was associated with significantly lower risk of in-hospital mortality (adjusted OR 0.971, 95%CI 0.959-0.982), and of five-year mortality (adjusted OR 0.970, 95%CI 0.962-0.977), respectively. Propensity score matching analysis yielded 870 pairs of patients with short ICU stay (2-5 days) and long ICU stay (>5 days) with balanced baseline, operative and postoperative variables. Patients with prolonged ICU stay (>5 days) had significantly lower in-hospital mortality (8.9% vs. 17.4%, <0.001) and 5-year mortality (28.2% vs. 30.7%, P=0.007) compared to patients with short ICU-stay (2-5 days). CONCLUSIONS: Prolonged ICU stay was common after surgery for acute TAAD. However, when adjusted for multiple baseline and operative variables as well as adverse postoperative events and the cluster effect of hospitals, it was associated with favorable survival up to 5 years after surgery.

A Proof of Concept Study on the Comfort and Usability of a Supportive Pillow for Pregnant Patients with COVID-19 Acute Respiratory Distress Syndrome.

Background: The prone position has been seen to benefit patients experiencing acute respiratory distress syndrome. However, performing this position in pregnant patients has been difficult and raises safety concerns. Objective: The current study aimed to test the use of a supportive pillow (Prone Pillow for Pregnant Patients or 4P) to address concerns regarding pregnant patients in prone position. Methods: The study prospectively evaluated the use of the prone pillow for patient comfort and usability among healthcare workers with qualitative and quantitative measures. Results: A total of three patients were recruited alongside 16 healthcare workers assisting pregnant patients to the prone position. Overall, awake pregnant patients found the pillow to be comfortable while healthcare workers perceived the pillow to be useful in improving quality of care among awake and intubated pregnant patients. CONCLUSION: The 4P is a potentially useful and beneficial product in placing pregnant patients in the prone position during episodes of acute respiratory distress. However, due to the limited sample size, more clinical trials are needed to evaluate the impact of this innovation in improving patient and healthcare worker safety.

Role of gender in short- and long-term outcomes after surgery for type A aortic dissection: analysis of a multicentre European registry.

OBJECTIVES: Gender difference in the outcome after type A aortic dissection (TAAD) surgery remains an issue of ongoing debate. In this study, we aimed to evaluate the impact of gender on the short- and long-term outcome after surgery for TAAD. METHODS: A multicentre European registry retrospectively included all consecutive TAAD surgery patients between 2005 and 2021 from 18 hospitals across 8 European countries. Early and late mortality, and cumulative incidence of aortic reoperation were compared between genders. RESULTS: A total of 3902 patients underwent TAAD surgery, with 1185 (30.4%) being females. After propensity score matching, 766 pairs of males and females were compared. No statistical differences were detected in the early postoperative outcome between genders. Ten-year survival was comparable between genders (47.8% vs 47.1%; log-rank test, P = 0.679), as well as cumulative incidences of distal or proximal aortic reoperations. Ten-year relative survival compared to country-, year-, age- and sex-matched general population was higher among males (0.65) compared to females (0.58). The time-period subanalysis revealed advancements in surgical techniques in both genders over the years. However, an increase in stroke was observed over time for both populations, particularly among females. CONCLUSIONS: The past 16 years have witnessed marked advancements in surgical techniques for TAAD in both males and females, achieving comparable early and late mortality rates. Despite these findings, late relative survival was still in favour of males.

Predicting prostate cancer grade reclassification on active surveillance using a deep Learning-Based grading algorithm.

Deep learning (DL)-based algorithms to determine prostate cancer (PCa) Grade Group (GG) on biopsy slides have not been validated by comparison to clinical outcomes. We used a DL-based algorithm, AIRAProstate, to re-grade initial prostate biopsies in two independent PCa active surveillance (AS) cohorts. In a cohort initially diagnosed with GG1 PCa using only systematic biopsies (n = 138), upgrading of the initial biopsy to ≥GG2 by AIRAProstate was associated with rapid or extreme grade reclassification on AS (odds ratio 3.3, p = .04), whereas upgrading of the initial biopsy by contemporary uropathologist reviews was not associated with this outcome. In a contemporary validation cohort that underwent prostate magnetic resonance imaging before initial biopsy (n = 169), upgrading of the initial biopsy (all contemporary GG1 by uropathologist grading) by AIRAProstate was associated with grade reclassification on AS (hazard ratio 1.7, p = .03). These results demonstrate the utility of a DL-based grading algorithm in PCa risk stratification for AS.

Longer prostate stromal cell telomere length is associated with increased risk of death from other cancers.

Background: Telomeres are located at chromosomal termini and function to maintain genomic integrity. Telomere dysfunction is a well-recognized contributor to aging and age-related diseases, such as prostate cancer. Since telomere length is highly heritable, we postulate that stromal cell telomere length in the tissue of a particular solid organ may generally reflect constitutive stromal cell telomere length in other solid organs throughout the body. Even with telomere loss occurring with each round of cell replication, in general, telomere length in prostate stromal cells in mid-life would still be correlated with the telomere length in stromal cells in other organs. Thus, we hypothesize that prostate stromal cell telomere length and/or telomere length variability is a potential indicator of the likelihood of developing future solid cancers, beyond prostate cancer, and especially lethal cancer. Methods: To explore this hypothesis, we conducted a cohort study analysis of 1,175 men who were surgically treated for prostate cancer and were followed for death, including from causes other than their prostate cancer. Results: In this cohort study with a median follow-up of 19 years, we observed that longer prostate stromal cell telomere length measured in tissue microarray spots containing prostate cancer was associated with an increased risk of death from other solid cancers. Variability in telomere length among these prostate stromal cells was possibly positively associated with risk of death from other solid cancers. Conclusion: Studying the link between stromal cell telomere length and cancer mortality may be important for guiding the development of cancer interception and prevention strategies.

Aortic arch surgery for DeBakey type 1 aortic dissection in patients aged 60 years or younger.

BACKGROUND: Extended aortic repair is considered a key issue for the long-term durability of surgery for DeBakey type 1 aortic dissection. The risk of aortic degeneration may be higher in young patients due to their long life expectancy. The early outcome and durability of aortic surgery in these patients were investigated in the present study. METHODS: The subjects of the present analysis were patients under 60 years old who underwent surgical repair for acute DeBakey type 1 aortic dissection at 18 cardiac surgery centres across Europe between 2005 and 2021. Patients underwent ascending aortic repair or total aortic arch repair using the conventional technique or the frozen elephant trunk technique. The primary outcome was 5-year cumulative incidence of reoperation on the distal aorta. RESULTS: Overall, 915 patients underwent surgical ascending aortic repair and 284 patients underwent surgical total aortic arch repair. The frozen elephant trunk procedure was performed in 128 patients. Among 245 propensity score-matched pairs, total aortic arch repair did not decrease the rate of distal aortic reoperation compared to ascending aortic repair (5-year cumulative incidence, 6.7% versus 6.7%, subdistributional hazard ratio 1.127, 95% c.i. 0.523 to 2.427). Total aortic arch repair increased the incidence of postoperative stroke/global brain ischaemia (25.7% versus 18.4%, P = 0.050) and dialysis (19.6% versus 12.7%, P = 0.003). Five-year mortality was comparable after ascending aortic repair and total aortic arch repair (22.8% versus 27.3%, P = 0.172). CONCLUSIONS: In patients under 60 years old with DeBakey type 1 aortic dissection, total aortic arch replacement compared with ascending aortic repair did not reduce the incidence of distal aortic operations at 5 years. When feasible, ascending aortic repair for DeBakey type 1 aortic dissection is associated with satisfactory early and mid-term outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04831073.

Overexpression of Fibroblast Activation Protein (FAP) in stroma of proliferative inflammatory atrophy (PIA) and primary adenocarcinoma of the prostate.

Fibroblast activation protein (FAP) is a serine protease upregulated at sites of tissue remodeling and cancer that represents a promising therapeutic and molecular imaging target. In prostate cancer, studies of FAP expression using tissue microarrays are conflicting, such that its clinical potential is unclear. Furthermore, little is known regarding FAP expression in benign prostatic tissues. Here we demonstrated, using a novel iterative multiplex IHC assay in standard tissue sections, that FAP was nearly absent in normal regions, but was increased consistently in regions of proliferative inflammatory atrophy (PIA). In carcinoma, FAP was expressed in all cases, but was highly heterogeneous. High FAP levels were associated with increased pathological stage and cribriform morphology. We verified that FAP levels in cancer correlated with CD163+ M2 macrophage density. In this first report to quantify FAP protein in benign prostate and primary tumors, using standard large tissue sections, we clarify that FAP is present in all primary prostatic carcinomas, supporting its potential clinical relevance. The finding of high levels of FAP within PIA supports the injury/regeneration model for its pathogenesis and suggests that it harbors a protumorigenic stroma. Yet, high levels of FAP in benign regions could lead to false positive FAP-based molecular imaging results in clinically localized prostate cancer.

A systematic review of the associations between protective behavioral strategies and heavy alcohol consumption and consequences among young adults.

OBJECTIVE: We systematically reviewed the literature to assess the association between use of alcohol protective behavioral strategies (PBS) and young adult heavy drinking and alcohol-related consequences. METHOD: We followed the preferred reporting items for systematic review and meta-analysis guidelines to select and review research studies that were comprised of a sample of young adults ages 18-26, included PBS derived from one of 10 validated scales as an independent variable, measured heavy alcohol use or alcohol consequences as the dependent variable, and tested the direct association between the two. Studies were gathered via PubMed, Scopus, Cumulative Index to Nursing and Allied Health Literature, APA PsycInfo, and Global Health. All identified study records underwent a two-step screening process and risk of bias assessment. RESULTS: Data were extracted from 94 studies that met inclusion criteria; 16 studies (17%) examined associations with heavy alcohol use and 91 studies (97%) tested effects of PBS on alcohol consequences. All studies that measured a total effect of PBS use (summations across all strategies) found significant negative associations with heavy alcohol use and 91% were negatively associated with alcohol consequences. Most studies that examined subscales of PBS found at least one significant, negative relation with heavy alcohol use (73%) and alcohol-related consequences (78%), though effects varied across type of subscale (e.g., manner of drinking). CONCLUSIONS: Our results support the use of PBS to address heavy alcohol consumption and related harms among young adults. Opportunities for refinement of current PBS in preventive interventions are discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Femoral arterial cannulation for surgical repair of stanford type A aortic dissection.

BACKGROUND: The benefits and harms associated with femoral artery cannulation over other sites of arterial cannulation for surgical repair of acute Stanford type A aortic dissection (TAAD) are not conclusively established. METHODS: We evaluated the outcomes after surgery for TAAD using femoral artery cannulation, supra-aortic arterial cannulation (i.e., innominate/subclavian/axillary artery cannulation), and direct aortic cannulation. RESULTS: 3751 (96.1%) patients were eligible for this analysis. In-hospital mortality using supra-aortic arterial cannulation was comparable to femoral artery cannulation (17.8% vs. 18.4%; adjusted OR 0.846, 95% CI 0.799-1.202). This finding was confirmed in 1028 propensity score-matched pairs of patients with supra-aortic arterial cannulation or femoral artery cannulation (17.5% vs. 17.0%, p = 0.770). In-hospital mortality after direct aortic cannulation was lower compared to femoral artery cannulation (14.0% vs. 18.4%, adjusted OR 0.703, 95% CI 0.529-0.934). Among 583 propensity score-matched pairs of patients, direct aortic cannulation was associated with lower rates of in-hospital mortality (13.4% vs. 19.6%, p = 0.004) compared to femoral artery cannulation. Switching of the primary site of arterial cannulation was associated with increased rate of in-hospital mortality (36.5% vs. 17.0%; adjusted OR 2.730, 95% CI 1.564-4.765). Ten-year mortality was similar in the study cohorts. CONCLUSIONS: In this study, the outcomes of surgery for TAAD using femoral arterial cannulation were comparable to those using supra-aortic arterial cannulation. However, femoral arterial cannulation was associated with higher in-hospital mortality than direct aortic cannulation. TRIAL REGISTRATION: ClinicalTrials.gov registration code: NCT04831073.

Do hypothetical evaluations of alcohol related consequences change over time? Examining the influence of past and ongoing consequences.

OBJECTIVE: Despite experiencing alcohol-related consequences, college students continue to drink at high rates. Hypothetical evaluations of alcohol-related consequences (i.e., evaluations of where potential/hypothetical consequences lie on a spectrum from extremely positive to extremely negative) may contribute to the maintenance of drinking patterns among students. The purpose of the present study was to describe hypothetical evaluations in a sample of students mandated to an alcohol intervention, examine changes over time, and investigate the influence of both baseline and time-varying experienced consequences. METHOD: This study was a secondary data analysis from a longitudinal randomized controlled trial. Participants were 474 mandated students (Mage = 18.65; 55.5 % male, 77.6 % White). Students completed an initial baseline assessment of demographics, alcohol use, consequences, and hypothetical evaluations, and 3-month and 9-month follow-up assessments that included hypothetical evaluations and experienced consequences. RESULTS: Hierarchical linear modeling (HLM) analyses revealed significant change in hypothetical evaluations over time such that they became less negative. A piecewise model demonstrated that this change happened between baseline and 3-month, with no additional change between 3-month and 9-month. The experience of consequences at baseline did not significantly moderate changes in either time interval. Time-varying consequences also had no significant effect on same-timepoint hypothetical evaluations. CONCLUSIONS: This study is the first to examine changes in hypothetical evaluations over time among mandated college students. Counter to expectations, hypothetical evaluations became less negative at 3-month follow-up. Though preliminary, findings add to the understanding of hypothetical evaluations of alcohol-related consequences.

Testing a brief, self-guided values affirmation for behavioral activation intervention during COVID-19.

This pilot study tested a single-session digital values affirmation for behavioral activation (VABA) intervention. Hypotheses predicted the VABA intervention would be more effective than an active control condition in improving mood, decreasing COVID-19 fear/worry and depressive symptoms, and promoting positively reinforcing behaviors during early weeks of the COVID-19 pandemic. Participants were a diverse sample of undergraduate students (N = 296) under a state-wide lockdown. Students were randomized to either VABA, a 10-min values clarification and affirmation task, or Control, a time- and attention-matched task. Positive and negative affects were assessed pre- and post-intervention. At next-day follow-up, positive and negative affects were reassessed, as well as past 24-h behavioral activation and depressive symptoms. Within-group increases in positive affect were observed in both conditions (VABA d = 0.39; Control d = 0.19). However, VABA produced a significantly larger increase than Control (F[2] = 3.856, p = .022, d = 0.22). At 24-h follow-up, behavioral activation, which was significantly higher in VABA versus Control (t[294] = -5.584, p < .001, d = 0.65), predicted fewer depressive symptoms (R2 change = .019, ß = -.134, p = .003). VABA is an ultra-brief intervention that appears to have acute effects on mood-enhancement and behavioral activation.

Nature of Neurological Complications and Outcome After Surgery for Type A Aortic Dissection.

Surgery for type A aortic dissection (TAAD) is frequently complicated by neurologic complications. The prognostic impact of neurologic complications of different nature has been investigated in this study. The subjects of this analysis were 3,902 patients who underwent surgery for acute TAAD from the multicenter European Registry of Type A Aortic Dissection (ERTAAD). During the index hospitalization, 722 patients (18.5%) experienced stroke/global brain ischemia. Ischemic stroke was detected in 539 patients (13.8%), hemorrhagic stroke in 76 patients (1.9%) and global brain ischemia in 177 patients (4.5%), with a few patients having had findings of more than 1 of these conditions. In-hospital mortality was increased significantly in patients with postoperative ischemic stroke (25.6%, adjusted odds ratio [OR] 2.422, 95% confidence interval [CI] 1.825 to 3.216), hemorrhagic stroke (48.7%, adjusted OR 4.641, 95% CI 2.524 to 8.533), and global brain ischemia (74.0%, adjusted OR 22.275, 95% CI 14.537 to 35.524) compared with patients without neurologic complications (13.5%). Similarly, patients who experienced ischemic stroke (46.3%, adjusted hazard ratio [HR] 1.719, 95% CI 1.434 to 2.059), hemorrhagic stroke (62.8%, adjusted HR 3.236, 95% CI 2.314 to 4.525), and global brain ischemia (83.9%, adjusted HR 12.777, 95% CI 10.325 to 15.810) had significantly higher 5-year mortality than patients without postoperative neurologic complications (27.5%). The negative prognostic effect of neurologic complications on survival vanished about 1 year after surgery. In conclusion, postoperative ischemic stroke, hemorrhagic stroke, and global cerebral ischemia increased early and midterm mortality after surgery for acute TAAD. The magnitude of risk of mortality increased with the severity of the neurologic complications, with postoperative hemorrhagic stroke and global brain ischemia being highly lethal complications.

Dramatic changes to well-known places go unnoticed.

How well do we know our city? It turns out, much more poorly than we might imagine. We used declarative memory and eye-tracking techniques to examine people's ability to detect modifications to real-world landmarks and scenes in Toronto locales with which they have had extensive experience. Participants were poor at identifying which scenes contained altered landmarks, whether the modification was to the landmarks' relative size, internal features, or relation to surrounding context. To determine whether an indirect measure would prove more sensitive, we tracked eye movements during viewing. Changes in overall visual exploration, but not to specific regions of change, were related to participants' explicit endorsement of scenes as modified. These results support the contention that very familiar landmarks are represented at a global or gist level, but not local or fine-grained, level. These findings offer a unified view of memory for gist across verbal and spatial domains, and across recent and remote memory, with implications for hippocampal-neocortical interactions.

Classification of the Urgency of the Procedure and Outcome of Acute Type A Aortic Dissection.

Surgery for type A aortic dissection (TAAD) is associated with a high risk of early mortality. The prognostic impact of a new classification of the urgency of the procedure was evaluated in this multicenter cohort study. Data on consecutive patients who underwent surgery for acute TAAD were retrospectively collected in the multicenter, retrospective European Registry of TAAD (ERTAAD). The rates of in-hospital mortality of 3,902 consecutive patients increased along with the ERTAAD procedure urgency grades: urgent procedure 10.0%, emergency procedure grade 1 13.3%, emergency procedure grade 2 22.1%, salvage procedure grade 1 45.6%, and salvage procedure grade 2 57.1% (p <0.0001). Preoperative arterial lactate correlated with the urgency grades. Inclusion of the ERTAAD procedure urgency classification significantly improved the area under the receiver operating characteristics curves of the regression model and the integrated discrimination indexes and the net reclassification indexes. The risk of postoperative stroke/global brain ischemia, mesenteric ischemia, lower limb ischemia, dialysis, and acute heart failure increased along with the urgency grades. In conclusion, the urgency of surgical repair of acute TAAD, which seems to have a significant impact on the risk of in-hospital mortality, may be useful to improve the stratification of the operative risk of these critically ill patients. This study showed that salvage surgery for TAAD is justified because half of the patients may survive to discharge.

Bipolar androgen therapy plus nivolumab for patients with metastatic castration-resistant prostate cancer: the COMBAT phase II trial.

Cyclic high-dose testosterone administration, known as bipolar androgen therapy (BAT), is a treatment strategy for patients with metastatic castration-resistant prostate cancer (mCRPC). Here, we report the results of a multicenter, single arm Phase 2 study (NCT03554317) enrolling 45 patients with heavily pretreated mCRPC who received BAT (testosterone cypionate, 400 mg intramuscularly every 28 days) with the addition of nivolumab (480 mg intravenously every 28 days) following three cycles of BAT monotherapy. The primary endpoint of a confirmed PSA50 response rate was met and estimated at 40% (N = 18/45, 95% CI: 25.7-55.7%, P = 0.02 one-sided against the 25% null hypothesis). Sixteen of the PSA50 responses were achieved before the addition of nivolumab. Secondary endpoints included objective response rate (ORR), median PSA progression-free survival, radiographic progression-free survival (rPFS), overall survival (OS), and safety/tolerability. The ORR was 24% (N = 10/42). Three of the objective responses occurred following the addition of nivolumab. After a median follow-up of 17.9 months, the median rPFS was 5.6 (95% CI: 5.4-6.8) months, and median OS was 24.4 (95% CI: 17.6-31.1) months. BAT/nivolumab was well tolerated, resulting in only five (11%) drug related, grade-3 adverse events. In a predefined exploratory analysis, clinical response rates correlated with increased baseline levels of intratumoral PD-1 + T cells. In paired metastatic tumor biopsies, BAT induced pro-inflammatory gene expression changes that were restricted to patients achieving a clinical response. These data suggest that BAT may augment antitumor immune responses that are further potentiated by immune checkpoint blockade.

Intensity and lifetime ratiometric luminescent thermometer based on a Tb(III) coordination polymer.

A three-dimensional terbium(III) coordination polymer of formula [Tb(bttb)0.5(2,5-pzdc)0.5]n (1) [H4bttb = 1,2,4,5-tetrakis(4'-carboxyphenyl)benzene and H2-2,5-pzdc = 2,5-pyrazinedicarboxylic acid] was obtained under hydrothermal conditions. The bttb4- tetraanion in 1 adopts the bridging and chelating-bridging pseudo-oxo coordination modes while the 2,5-pzdc2- dianion exhibits a rather unusual bis-bidentate bridging pseudo-oxo coordination mode, both ligands being responsible for the stiffness of the resulting 3D structure. Solid-state photoluminescent measurements illustrate that 1 exhibits remarkable green luminescence emission, the most intense band occurring in the region of 550 nm (5D4 → 7F5) with lifetimes at the millisecond scale. Thermometric performances of 1 reveal a maximum relative sensitivity (Sm) of 0.76% K-1 at 295 K (δT = 0.05 K), constituting a TbIII ratiometric solid luminescent thermometer over the physiological temperature range. Variable-temperature static (dc) magnetic susceptibility measurements for 1 in the temperature range 2.0-300 K show the expected behavior for the depopulation of the splitted mJ levels of the 7F7 ground state of the magnetically anisotropic terbium(III) ion plus a weak antiferromagnetic interaction through the carboxylate bridges. No significant out-of-phase magnetic susceptibility signals were observed for 1 in the temperature range 2.0-10.0 K, either in the absence or presence of a static dc magnetic field.

Environmentally friendly concrete block production: valorization of civil construction and chemical industry waste.

In the present work, a study was carried out on the dosage of wastes from the chemical industry (tannery sludge) and civil construction (concrete and plaster) in mixtures used in concrete blocks' production. The objective was the application of these blocks in paving. The characterization of the materials used was performed employing X-ray diffractometry (XRD), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDS). The effect of the different residues on the blocks' properties was evaluated through compressive strength, flexion-traction, water absorption, abrasion resistance, and leaching tests. The results indicated that the concrete paving blocks produced with the addition of residues did not obtain gains in the values of mechanical resistance to compression and traction in bending compared to blocks made with standard raw material. However, the blocks produced with construction waste presented satisfactory results for application in street paving after 7 days of concrete curing, reaching values between 36.54 and 44.6 MPa for the mentioned properties. These values also increased to 21.4% within 28 days of curing. The blocks produced with plaster showed values between 37.03 and 39.85 MPa after 28 days of curing, allowing their use for street paving. On the other hand, the blocks containing residues from the chemical industry had lower strengths, reaching a maximum of 29.36 MPa after 28 days of curing. In addition, it was also noted that the blocks produced with recycled concrete showed an improvement in performance for a composition of 50% recycled material.

Does self-affirmation augment the effects of a mandated personalized feedback intervention? A randomized controlled trial with heavy drinking college students.

OBJECTIVE: Theory and evidence indicate that affirming the value of the self before exposure to a threatening message fosters more open-minded appraisal of message content. We predicted that college students mandated to a computer-delivered personalized feedback intervention (PFI) and who engaged in a self-affirmation (SA) exercise would demonstrate reduce drinking and consequences relative to those who received an attention control. METHOD: Participants were 484 undergraduates (age 18-24, 56% male, 78% White) mandated to participate in an alcohol intervention following a first-time alcohol policy violation. After a baseline assessment, each was randomized to SA (n = 256) or attention control (n = 227) prior to a computer-delivered PFI intervention. Posttest measures included an affirmation manipulation check; primary outcomes (past month weekly quantity, peak drinks, binge frequency, consequences) were assessed at 1-, 3-, 6-, 9-, and 12-month follow-ups. We used latent growth curve modeling to test study hypotheses. RESULTS: The SA exercise increased positive self-evaluation at posttest (p < .001). Overall reductions in drinking and consequences were observed at early follow-up (all p < .05), but the SA manipulation was not associated with intercept or slope factor differences in the models. Engaging in assessments during COVID restrictions was generally associated with reduced drinking and consequences. CONCLUSIONS: The SA exercise did not differentially affect trajectories of alcohol use and consequences, despite evidence that the exercise had the predicted effect on participant's self-evaluations. The lack of SA effects could be attributed to a nonthreatening PFI intervention that is generally accepted among mandated students. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Divergent immune microenvironments in two tumor nodules from a patient with mismatch repair-deficient prostate cancer.

Patients with prostate cancer (PC) generally do not respond favorably to immune checkpoint inhibitors, which may be due to a low abundance of tumor-infiltrating lymphocytes even when mutational load is high. Here, we identified a patient who presented with high-grade primary prostate cancer with two adjacent tumor nodules. While both nodules were mismatch repair-deficient (MMRd), exhibited pathogenic MSH2 and MSH6 alterations, had a high tumor mutational burden (TMB), and demonstrated high microsatellite instability (MSI), they had markedly distinct immune phenotypes. The first displayed a dense infiltrate of lymphocytes ("hot nodule"), while the second displayed significantly fewer infiltrating lymphocytes ("cold nodule"). Whole-exome DNA analysis found that both nodules shared many identical mutations, indicating that they were derived from a single clone. However, the cold nodule appeared to be sub-clonal relative to the hot nodule, suggesting divergent evolution of the cold nodule from the hot nodule. Whole-transcriptome RNA analysis found that the cold nodule demonstrated lower expression of genes related to antigen presentation (HLA) and, paradoxically, classical tumor immune tolerance markers such as PD-L1 (CD274) and CTLA-4. Immune cell deconvolution suggested that the hot nodule was enriched not only in CD8+ and CD4 + T lymphocytes, but also in M1 macrophages, activated NK cells, and γδ T cells compared to the cold nodule. This case highlights that MMRd/TMB-high PC can evolve to minimize an anti-tumor immune response, and nominates downregulation of antigen presentation machinery (HLA loss) as a potential mechanism of adaptive immune evasion in PC.