Experience-dependent evolution of odor mixture representations in piriform cortex.

Rodents can learn from exposure to rewarding odors to make better and quicker decisions. The piriform cortex is thought to be important for learning complex odor associations; however, it is not understood exactly how it learns to remember discriminations between many, sometimes overlapping, odor mixtures. We investigated how odor mixtures are represented in the posterior piriform cortex (pPC) of mice while they learn to discriminate a unique target odor mixture against hundreds of nontarget mixtures. We find that a significant proportion of pPC neurons discriminate between the target and all other nontarget odor mixtures. Neurons that prefer the target odor mixture tend to respond with brief increases in firing rate at odor onset compared to other neurons, which exhibit sustained and/or decreased firing. We allowed mice to continue training after they had reached high levels of performance and find that pPC neurons become more selective for target odor mixtures as well as for randomly chosen repeated nontarget odor mixtures that mice did not have to discriminate from other nontargets. These single unit changes during overtraining are accompanied by better categorization decoding at the population level, even though behavioral metrics of mice such as reward rate and latency to respond do not change. However, when difficult ambiguous trial types are introduced, the robustness of the target selectivity is correlated with better performance on the difficult trials. Taken together, these data reveal pPC as a dynamic and robust system that can optimize for both current and possible future task demands at once.

The relationship of cancer history and chronic disease status to colorectal cancer screening: A cross-sectional analysis of 2020-2021 Behavioral Risk Factor Surveillance System.

PURPOSE: We examined whether having a history of cancer and chronic diseases was associated with guideline-concordant colorectal cancer (CRC) screening utilization. METHODS: Self-reported data from the 2020 and 2021 Behavioral Risk Factor Surveillance System in Oregon and West Virginia were used. Guideline-concordant CRC screening was the outcome of interest. The exposure was having a personal history of cancer, chronic diseases, or both. Multivariable logistic regressions were applied to assess the abovementioned association. RESULTS: Among 10,373 respondents aged 45-75 years, 75.5% of those with a history of cancer and chronic diseases had guideline-concordant CRC screening use versus 52.8% of those without any history (p-value < 0.05). In multivariable analysis, having a history of cancer (OR 1.74; 95% CI 1.11-2.71), chronic diseases (OR 1.35; 95% CI 1.14-1.59), and both cancer and chronic diseases (OR 2.14; 95% CI 1.62-2.82) were positively associated with screening uptake compared to respondents without any history. Regardless of disease history, older age was associated with greater CRC screening uptake (p-value < 0.05). Among respondents with chronic diseases only or without any condition, those with a health care provider had 1.7-fold and 2.7-fold increased odds of receiving CRC screening, respectively. However, current smokers were 28% and 34% less likely to be screened for CRC among those with chronic diseases only and without any conditions, respectively. CONCLUSION: Having a personal history of cancer and chronic diseases appears to be positively associated with guideline-concordant CRC screening use. Effective implementation of patient-centered communication through primary care initiatives may increase adherence to CRC screening recommendations.

Single Center Experience with the JETi Hydrodynamic Thrombectomy System for Acute Limb Ischemia.

OBJECTIVE: Acute limb ischemia (ALI) remains a vascular emergency with high morbidity and mortality. While the JETi Hydrodynamic Thrombectomy System (Abbott, Abbott Park, IL) offers a percutaneous approach to fragment and aspirate thrombus in patients with arterial occlusions, data on its efficacy and safety is limited. This study reports our early experience using the JETi device to treat ALI at our institution. METHODS: This is a single-center retrospective review of ALI patients treated with the JETi device between September 2020 and December 2022. Patients were included if the JETi device was used either as primary intervention or as an adjunct procedure. The primary endpoint was technical success defined as <50% residual thrombus post-intervention. Secondary endpoints included achieving complete resolution of the thrombus on angiogram, acute kidney injury (AKI), major bleeding, 30-day major amputation, and 30-day mortality. RESULTS: A total of 59 JETi procedures for ALI (mean age 62 years [IQR 56,71]) were performed on 39 males and 20 females. Median time from onset of symptoms to hospitalization was 24 hours (IQR 4-168). Rutherford classifications were I (10), IIa (27), IIb (14) and undocumented (8). Etiology of ALI was native vessel thrombosis (27), embolism (16), graft/stent thrombosis (14), and iatrogenic (2). A total of 124 vessels were treated, with an average of 2.1 vessels per procedure. The primary outcome was achieved in 86% (107/124) of the arteries, with 82% (102/124) successfully opened using the JETi device alone without the need for any adjunctive therapy. Complete resolution of the thrombus using JETi was achieved in 81% (101/124) arteries, with or without the use of adjunctive therapy. 6.7% (4/59) of patients required a major limb amputation within 30 days despite successful recanalization, and one 30-day mortality was recorded. Complications included distal embolization (5), access site hematoma (2), and acute kidney injury (4). No major bleeding, hemolysis-induced AKI, or vessel dissection or perforation were observed. CONCLUSION: The JETi device appears to be a safe and effective percutaneous treatment option in the management of ALI. It provides definitive treatment with a high technical success rate of 86% and a good safety profile.

PATIENTS WITH ACUTE LOWER LIMB ISCHEMIA CONTINUE TO HAVE SIGNIFICANT MORBIDITY AND MORTALITY.

BACKGROUND: The treatment of acute lower limb ischemia (ALLI) has evolved over the last several decades with the availability of several new treatment modalities. This study was undertaken to evaluate the contemporary presentation and outcomes of ALLI patients. METHODS: We retrospectively analyzed data from a prospectively collected database of all patients who presented to our tertiary referral hospital with acute ischemia of the lower extremity between May 2016 and October 2020. The cause of death was obtained from the Michigan State Death Registry. RESULTS: During the study period, 233 patients (251 lower limbs) were evaluated for ALLI. Seventy-three percent had thrombotic occlusion 24% had embolic occlusion, and 3% due to a low-flow state. Rutherford classification of ischemia severity was 7%, 49%, 40%, and 4% for Rutherford grade I, IIA, IIB, and III, respectively. Five percent underwent primary amputations, and 6% received medical therapy only. The mean length of stay was 11 ± 9 days. Nineteen percent of patients were readmitted within 30 days of discharge. At 30 days postoperatively, mortality was 9% and limb loss was 19%. On multivariate analysis, one or no vessel runoff to the foot post-operatively was associated with higher 30-day limb loss. Patients with no run-off vessels post-operatively had significantly higher 30-day mortality. Cardiovascular complications accounted for most deaths (48%). At 1-year postoperatively, mortality and limb loss reached 17% and 34%, respectively. CONCLUSION: Despite advances in treatment modalities and cardiovascular care, patients presenting with ALLI continue to have high mortality, limb loss, and readmission rates at 30 days.

Cancer Diagnoses After Recent Weight Loss.

Importance: Weight loss is common in primary care. Among individuals with recent weight loss, the rates of cancer during the subsequent 12 months are unclear compared with those without recent weight loss. Objective: To determine the rates of subsequent cancer diagnoses over 12 months among health professionals with weight loss during the prior 2 years compared with those without recent weight loss. Design, Setting, and Participants: Prospective cohort analysis of females aged 40 years or older from the Nurses' Health Study who were followed up from June 1978 until June 30, 2016, and males aged 40 years or older from the Health Professionals Follow-Up Study who were followed up from January 1988 until January 31, 2016. Exposure: Recent weight change was calculated from the participant weights that were reported biennially. The intentionality of weight loss was categorized as high if both physical activity and diet quality increased, medium if only 1 increased, and low if neither increased. Main Outcome and Measures: Rates of cancer diagnosis during the 12 months after weight loss. Results: Among 157 474 participants (median age, 62 years [IQR, 54-70 years]; 111 912 were female [71.1%]; there were 2631 participants [1.7%] who self-identified as Asian, Native American, or Native Hawaiian; 2678 Black participants [1.7%]; and 149 903 White participants [95.2%]) and during 1.64 million person-years of follow-up, 15 809 incident cancer cases were identified (incident rate, 964 cases/100 000 person-years). During the 12 months after reported weight change, there were 1362 cancer cases/100 000 person-years among all participants with recent weight loss of greater than 10.0% of body weight compared with 869 cancer cases/100 000 person-years among those without recent weight loss (between-group difference, 493 cases/100 000 person-years [95% CI, 391-594 cases/100 000 person-years]; P < .001). Among participants categorized with low intentionality for weight loss, there were 2687 cancer cases/100 000 person-years for those with weight loss of greater than 10.0% of body weight compared with 1220 cancer cases/100 000 person-years for those without recent weight loss (between-group difference, 1467 cases/100 000 person-years [95% CI, 799-2135 cases/100 000 person-years]; P < .001). Cancer of the upper gastrointestinal tract (cancer of the esophagus, stomach, liver, biliary tract, or pancreas) was particularly common among participants with recent weight loss; there were 173 cancer cases/100 000 person-years for those with weight loss of greater than 10.0% of body weight compared with 36 cancer cases/100 000 person-years for those without recent weight loss (between-group difference, 137 cases/100 000 person-years [95% CI, 101-172 cases/100 000 person-years]; P < .001). Conclusions and Relevance: Health professionals with weight loss within the prior 2 years had a significantly higher risk of cancer during the subsequent 12 months compared with those without recent weight loss. Cancer of the upper gastrointestinal tract was particularly common among participants with recent weight loss compared with those without recent weight loss.

Impact of Axillary Lymph Node Dissection and Sentinel Lymph Node Biopsy on Upper Limb Morbidity in Breast Cancer Patients: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the impact of axillary lymph node dissection (ALND) and sentinel lymph node biopsy (SLNB) on upper limb (UL) morbidity in breast cancer patients. BACKGROUND: Axillary de-escalation is motivated by a desire to reduce harm of ALND. Understanding the impact of axillary surgery and disparities in operative procedures on postoperative arm morbidity would better direct resources to the point of need and cement the need for de-escalation strategies. METHODS: Embase, MEDLINE, CINAHL, and PsychINFO were searched from 1990 until March 2020. Included studies were randomized-controlled and observational studies focusing on UL morbidities, in breast surgery patients. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The prevalence of UL morbidity comparing SLNB and ALND at <12 months, 12 to 24 months, and beyond 24 months were analyzed. RESULTS: Sixty-seven studies were included. All studies reported a higher rate of lymphedema and pain after ALND compared with SLNB. The difference in lymphedema and pain prevalence between SLNB and ALND was 13.7% (95% confidence interval: 10.5-16.8, P <0.005) and 24.2% (95% confidence interval: 12.1-36.3, P <0.005), respectively. Pooled estimates for prevalence of reduced strength and range of motion after SLNB and ALND were 15.2% versus 30.9% and 17.1% versus 29.8%, respectively. Type of axillary surgery, greater body mass index, and radiotherapy were some of the predictors for UL morbidities. CONCLUSIONS: Prevalence of lymphedema after ALND was higher than previously estimated. ALND patients experienced greater rates of lymphedema, pain, reduced strength, and range of motion compared with SLNB. The findings support the continued drive to de-escalate axillary surgery.

Left subclavian artery revascularization is associated with less neurologic injury after endovascular repair of acute type B aortic dissection.

OBJECTIVE: The aim of this study was to analyze patients with acute type B aortic dissection (aTBAD) requiring thoracic endovascular aortic repair (TEVAR) with left subclavian artery (LSA) coverage to determine whether LSA revascularization decreased the risk of neurologic complications. METHODS: The national Vascular Quality Initiative TEVAR module was queried for all procedures performed between 2014 and 2021. Patients presenting with aortic aneurysms or aortic ruptures were excluded from the analysis. Patients were divided into two groups according to whether their LSA was revascularized (prior to or during TEVAR) or not. Univariate followed by multivariate analysis was used to account for possible confounders and evaluate the association of LSA revascularization with the primary outcome of neurologic injury (stroke or spinal cord ischemia). RESULTS: Among patients who had TEVAR for aTBAD, 501 patients had the LSA covered. The LSA was revascularized prior to or concomitant with TEVAR in 28% of these patients (n = 139). Average age was 57 years, and 73% (n = 366) were male. Neurologic injury developed in 88 patients (18%). On univariate analysis, patients who had their LSA revascularized were significantly less likely to develop neurologic injury (10% vs 20%; P < .01). This association persisted after accounting for potential confounders (odds ratio, 0.4; P = .02). No significant difference was seen when comparing 30-day or 1-year mortality between patients who had LSA revascularization and those who did not. Follow-up averaged 1.9 years (range, 0-8.1 years). Long-term survival did not differ between the two groups on Kaplan-Meier analysis. CONCLUSIONS: In this study of patients with aTBAD who underwent LSA coverage during TEVAR, the addition of a LSA revascularization procedure was associated with a significantly lower incidence of neurological injury including spinal cord ischemia and/or stroke.

International, prospective cohort study comparing non-absorbable versus absorbable sutures for skin surgery: CANVAS service evaluation.

BACKGROUND: Absorbable or non-absorbable sutures can be used for superficial skin closure following excisional skin surgery. There is no consensus among clinicians nor high-quality evidence supporting the choice of suture. The aim of the present study was to determine current suture use and complications at 30 days after excisional skin surgery. METHODS: An international, prospective service evaluation of adults undergoing excision of skin lesions (benign and malignant) in primary and secondary care was conducted from 1 September 2020 to 15 April 2021. Routine patient data collected by UK and Australasian collaborator networks were uploaded to REDCap©. Choice of suture and risk of complications were modelled using multivariable logistic regression. RESULTS: Some 3494 patients (4066 excisions) were included; 3246 (92.9 per cent) were from the UK and Ireland. Most patients were men (1945, 55.7 per cent), Caucasian (2849, 81.5 per cent) and aged 75-84 years (965, 27.6 per cent). The most common clinical diagnosis was basal cell carcinoma (1712, 42.1 per cent). Dermatologists performed most procedures, with 1803 excisions (44.3 per cent) on 1657 patients (47.4 per cent). Most defects were closed primarily (2856, 81.9 per cent), and there was equipoise in regard to use of absorbable (2127, 57.7 per cent) or non-absorbable (1558, 42.2 per cent) sutures for superficial closure. The most common complications were surgical-site infection (103, 2.9 per cent) and delayed wound healing (77, 2.2 per cent). In multivariable analysis, use of absorbable suture type was associated with increased patient age, geographical location (UK and Ireland), and surgeon specialty (oral and maxillofacial surgery and plastic surgery), but not with complications. CONCLUSION: There was equipoise in suture use, and no association between suture type and complications. Definitive evidence from randomized trials is needed.

Drug-induced acute pancreatitis due to medications used for inflammatory bowel disease: A VigiBase pharmacovigilance database study.

BACKGROUND: Nearly all medications used for inflammatory bowel disease (IBD) have been reported as causes of acute pancreatitis (AP), with the thiopurines being among the most frequently described. However, with the development of newer medications, thiopurine monotherapy has largely been replaced by newer immunosuppressive drugs. There are few data on the association between AP and biologic/small molecule agents. METHODS: VigiBase, the World Health Organization's Global Individual Case Safety Report database, was used to assess the association between AP and common IBD medications. A case/non-case disproportionality analysis was performed and disproportionality signals were reported as a reporting odds ratio (ROR) with 95% confidence intervals (CIs). RESULTS: A total of 4,223 AP episodes were identified for common IBD medications. Azathioprine (ROR 19.18, 95% CI 18.21-20.20), 6-mercaptopurine (ROR 13.30, 95% CI 11.73-15.07), and 5-aminosalicylic acid (ROR 17.44, 95% CI 16.24-18.72) all had strong associations with AP, while the biologic/small molecule agents showed weaker or no disproportionality. The association with AP was much higher for thiopurines when used for Crohn's disease (ROR 34.61, 95% CI 30.95-38.70) compared to ulcerative colitis (ROR 8.94, 95% CI 7.47-10.71) or rheumatologic conditions (ROR 18.87, 95% CI 14.72-24.19). CONCLUSIONS: We report the largest real-world database study investigating the association between common IBD medications and AP. Among commonly used IBD medications including biologic/small molecule agents, only thiopurines and 5-aminosalicylic acid are strongly associated with AP. The association between thiopurines and AP is much stronger when the drug is used for Crohn's disease compared to ulcerative colitis and rheumatologic conditions.

Lifestyle and personal factors associated with having macroscopic residual disease after ovarian cancer primary cytoreductive surgery.

OBJECTIVE: The presence of macroscopic residual disease after primary cytoreductive surgery (PCS) is an important factor influencing survival for patients with high-grade serous ovarian cancer (HGSC). More research is needed to identify factors associated with having macroscopic residual disease. We analyzed 12 lifestyle and personal exposures known to be related to ovarian cancer risk or inflammation to identify those associated with having residual disease after surgery. METHODS: This analysis used data on 2054 patients with advanced stage HGSC from the Ovarian Cancer Association Consortium. The exposures were body mass index, breastfeeding, oral contraceptive use, depot-medroxyprogesterone acetate use, endometriosis, first-degree family history of ovarian cancer, incomplete pregnancy, menopausal hormone therapy use, menopausal status, parity, smoking, and tubal ligation. Logistic regression models were fit to assess the association between these exposures and having residual disease following PCS. RESULTS: Menopausal estrogen-only therapy (ET) use was associated with 33% lower odds of having macroscopic residual disease compared to never use (OR = 0.67, 95%CI 0.46-0.97, p = 0.033). Compared to nulliparous women, parous women who did not breastfeed had 36% lower odds of having residual disease (OR = 0.64, 95%CI 0.43-0.94, p = 0.022), while there was no association among parous women who breastfed (OR = 0.90, 95%CI 0.65-1.25, p = 0.53). CONCLUSIONS: The association between ET and having no macroscopic residual disease is plausible given a strong underlying biologic hypothesis between this exposure and diagnosis with HGSC. If this or the parity finding is replicated, these factors could be included in risk stratification models to determine whether HGSC patients should receive PCS or neoadjuvant chemotherapy.

Necessity, Role, and Outcomes of Fasciotomy in Patients with Acute Limb Ischemia.

BACKGROUND: The incidence of compartment syndrome in patients with acute lower limb ischemia (ALLI) and the effects of fasciotomy on outcomes are largely undefined. This study aimed to define the incidence of compartment syndrome in patients with ALLI and to examine whether different fasciotomy strategies are associated with specific patient outcomes. METHODS: A single-center retrospective study of patients who had ALLI between April 2016 and October 2020 at a tertiary care center. Patients were categorized into groups as having received early and late therapeutic fasciotomy (TF), early prophylactic fasciotomy (PF), early exploratory fasciotomy, and no fasciotomy. Primary outcome was 30-day amputation rate. Secondary outcomes were 30-day and 1-year mortality, 1-year amputation rate, and length of stay. Groups were compared using descriptive statistics to assess the association of fasciotomy approach with outcomes. RESULTS: During the study period, 266 patients were treated for ALLI, and 62 patients (23%) underwent 66 fasciotomies. A total of 41 TF, 23 PF, and 2 exploratory fasciotomies were done. There were 58 early fasciotomies performed (88% of 66 limbs): 33 (57%) early TF, 23 (40%) PF, and 2 (3%) exploratory. There were 8 patients who developed compartment syndrome after their revascularization operation and received delayed TF (12% of 66 limbs). The total number of TF was 41, which was 15% of all ALLI patients. The mean ± SD time to fasciotomy closure was 6.7 ± 5.7 days, which did not differ between PF and TF groups. Significantly more patients in the TF group had an amputation at 30 days (11 [29%] vs. 1 [5%]; P = 0.03) and at 1 year (6 [18%] vs. 2 [9%]; P = 0.02) than those in the PF group. Length of stay was increased in both TF (16 days) and PF (19 days) patients compared to nonfasciotomy patients (10 days; P < 0.01) but did not differ between the 2 fasciotomy groups (P = 0.4). Thirty-day limb loss was highest in patients who underwent early TF (10/33, 33%), intermediate in those with delayed TF (1/8, 13%), and lowest in PF (1/23, 5%; P = 0.03). CONCLUSIONS: Approximately 15% of patients with ALLI in our cohort required a TF for compartment syndrome. Close postoperative monitoring of ALLI patients who did not undergo early fasciotomy did detect delayed compartment syndrome; however, this approach did not prevent limb loss. To optimize limb salvage, physicians treating patients with ALLI should be experienced in how to recognize and treat compartment syndrome.

Cross-clamp location and perioperative outcomes after open infrarenal abdominal aortic aneurysm repair: A Vascular Quality Initiative® review.

OBJECTIVES: By analyzing national Vascular Quality Initiative (VQI) data for patients undergoing open infrarenal abdominal aortic aneurysms (AAA) repair, we sought to better characterize the effects of different suprarenal clamping positions on postoperative outcomes. METHODS: We performed a retrospective analysis of a prospectively collected national VQI database for all open infrarenal AAA repairs performed between 2003 and 2017. Patients were initially divided into proximal (above 1 renal, above 2 renals, and supraceliac) and infrarenal clamp groups. Patients were then subdivided into those who underwent surgery between 2003-2010 and those who had surgery between 2011-2017. Univariate followed by multivariate analyses were done to compare the baseline characteristics, preoperative, intraoperative, and postoperative outcomes between the two groups. RESULTS: During the study period, 9068 open AAA repairs were recorded in the VQI; of these, 5043 met the inclusion criteria. Aortic clamp level was infrarenal in 59% (N = 2975), above 1 renal in 15% (N = 735), above both renals in 21% (N = 1053), and supraceliac in 5% (N = 280). The average age was 69 years, and males comprised 73% (N = 3701) of the cohort. The overall 30-day mortality for the entire study group was 2.7%. On univariate analysis, patients who underwent proximal clamping had significantly higher 30-day mortality than those undergoing infrarenal clamping (3.7 vs 2.0%, p < 0.001). After adjusting for preoperative and intraoperative variables, this difference became nonsignificant. On multivariate analysis, clamping above both renals or the celiac artery was associated with an increased occurrence of postoperative myocardial infarction (odds ratio = 1.44, p = 0.037 and odds ratio = 1.78, p = 0.023, respectively). All proximal clamp positions were associated with a significant increase in the incidence of AKI and renal failure requiring dialysis. There was no significant difference when looking at overall survival times comparing the suprarenal and infrarenal clamp position groups (p = 0.1). Patients who underwent surgery in the latter half of the study period had longer intraoperative renal ischemia time, increased in estimated blood loss, and longer total procedure time. CONCLUSIONS: Suprarenal clamping, at any level, was associated with an increased risk of AKI and renal replacement therapy. Clamping above both renal and celiac arteries was associated with increased cardiac morbidity. Perioperative and long-term mortality was unaffected by clamp level. Patients operating in the latter half of the study had increased estimated blood loss, renal ischemia time, and operative time, which may reflect decreased training in open AAA repair. During open AAA repair, the proximal clamp site should be chosen based on anatomic considerations and not a perceived perioperative mortality benefit. Proximal aortic clamping should always be performed at the safest, distal-most level to reduce cardiac morbidity and the risk of postoperative dialysis.

EPG research and therapy: further developments.

Electropalatography (EPG) has been used in the past 50 years for studying the patterns of contact between the tongue and the palate during speech production in typical speakers and those with speech disorders due to different causes. At the 7th EPG Symposium in Japan that was held online on 24 January 2021 (see: https://epg-research.sakura.ne.jp/), a panel of invited experts discussed their views regarding further developments and application of the technique. This paper provides a summary of this discussion. EPG offers information on articulation which cannot be replaced by other instrumental measures of speech. Identified areas for further hardware development are thinner EPG plates, better dental and palatal coverage, wireless connectivity, and sensors that provide additional articulatory information (e.g. tongue pressure, tongue-palate distance). EPG can serve as a resource for teaching speech disorders and phonetics. Furthermore, EPG therapy can be combined with telepractice in the speech therapy of clients with speech disorders.

Auditory-perceptual evaluation with visual analogue scale: feasibility and preliminary evidence of ultrasound visual feedback treatment of Finnish [r].

Accumulating evidence suggests that ultrasound visual feedback increases the treatment efficacy for persistent speech sound errors. However, the available evidence is mostly from English. This is a feasibility study of ultrasound visual feedback for treating distortion of Finnish [r]. We developed a web-based application for auditory-perceptual judgement. We investigated the impact of listener's experience on perceptual judgement and the intra-rater reliability of listeners. Four boys (10-11 years) with distortion of [r], otherwise typical development, partook in eight ultrasound treatment sessions. In total, 117 [r] samples collected at pre- and post-intervention were judged with visual analogue scale (VAS) by two listener groups: five speech and language therapists (SLTs) and six SLT students. We constructed a linear mixed-effects model with fixed effects for time and listener group and several random effects. Our findings indicate that measurement time had a significant main effect on judgement results, χ2 = 78.82, p < 0.001. Effect of listener group was non-significant, but a significant main effect of interaction of group × time, χ2 = 6.33, p < 0.012 was observed. We further explored the effect of group with nested models, and results revealed a non-significant effect of group. The average intra-rater correlation of the 11 listeners was 0.83 for the pre-intervention samples and 0.92 for post-intervention showing a good or excellent degree of agreement. Finnish [r] sound can be evaluated with VAS and ultrasound visual feedback is a feasible and promising method in treatment for distortion of [r], and its efficacy should be further assessed.

Prefrontal cortical neurons are selective for non-local hippocampal representations during replay and behavior.

Diverse functions such as decision-making and memory consolidation may depend upon communication between neurons in hippocampus (HP) and prefrontal cortex (PFC). HP replay is a candidate mechanism to facilitate this communication, however details remain largely unknown due to the technical challenges of recording sufficient numbers of HP neurons for replay while also recording PFC neurons. Here we implanted male rats with 40-tetrode drives, split between HP and PFC, during learning of a Y-maze spatial memory task. Surprisingly, we found that in contrast to their non-selectivity for maze arm during movement, a portion of PFC neurons were highly selective for HP replay of different arms. Moreover, PFC neurons' selectivity to HP non-local arm representation during running tended to match their replay arm selectivity and was predictive of future choice. Thus, PFC activity that is tuned to HP activity is best explained by non-local HP position representations rather than HP representation of actual position, providing a new potential mechanism of HP-PFC coordination during HP replay.SIGNIFICANCE STATEMENTThe hippocampus is implicated in spatial learning while the prefrontal cortex is implicated in decision-making. The question of how the two areas interact has been of great interest. A specific activity type in hippocampus called replay is particularly interesting because it resembles internal exploration of non-local experiences, but is technically challenging to study, requiring recordings from large numbers of hippocampus neurons simultaneously. Here we combined replay recordings from hippocampus with prefrontal recordings, to reveal a surprising degree of selectivity for replay, and a pattern of coordination that supports some conceptions of hippocampocortical interaction and challenges others.

Artificial Intelligence-based Radiomics in the Era of Immuno-oncology.

The recent, rapid advances in immuno-oncology have revolutionized cancer treatment and spurred further research into tumor biology. Yet, cancer patients respond variably to immunotherapy despite mounting evidence to support its efficacy. Current methods for predicting immunotherapy response are unreliable, as these tests cannot fully account for tumor heterogeneity and microenvironment. An improved method for predicting response to immunotherapy is needed. Recent studies have proposed radiomics-the process of converting medical images into quantitative data (features) that can be processed using machine learning algorithms to identify complex patterns and trends-for predicting response to immunotherapy. Because patients undergo numerous imaging procedures throughout the course of the disease, there exists a wealth of radiological imaging data available for training radiomics models. And because radiomic features reflect cancer biology, such as tumor heterogeneity and microenvironment, these models have enormous potential to predict immunotherapy response more accurately than current methods. Models trained on preexisting biomarkers and/or clinical outcomes have demonstrated potential to improve patient stratification and treatment outcomes. In this review, we discuss current applications of radiomics in oncology, followed by a discussion on recent studies that use radiomics to predict immunotherapy response and toxicity.

Noncontrast MRI for Hepatocellular Carcinoma Detection: A Systematic Review and Meta-analysis - A Potential Surveillance Tool?

BACKGROUND AND AIMS: This meta-analysis investigates the diagnostic performance of non-contrast magnetic resonance imaging (MRI) for the detection of hepatocellular carcinoma (HCC). METHODS: A systematic review was performed to May 2020 for studies which examined the diagnostic performance of non-contrast MRI (multi-sequence or diffusion-weighted imaging (DWI)- alone) for HCC detection in high risk patients. The primary outcome was accuracy for the detection of HCC. Random effects models were used to pool outcomes for sensitivity, specificity, positive likelihood ratio (LR) and negative LR. Subgroup analyses for cirrhosis and size of the lesion were performed. RESULTS: Twenty-two studies were included involving 1685 patients for per-patient analysis and 2128 lesions for per-lesion analysis. Multi-sequence non-contrast MRI (NC-MRI) using T2+DWI±T1 sequences had a pooled per-patient sensitivity of 86.8% (95%CI:83.9-89.4%), specificity of 90.3% (95%CI:87.3-92.7%), and negative LR of 0.17 (95%CI:0.14-0.20). DWI-only MRI (DW-MRI) had a pooled sensitivity of 79.2% (95%CI:71.8-85.4%), specificity of 96.5% (95%CI:94.3-98.1%) and negative LR of 0.24 (95%CI:1.62-0.34). In patients with cirrhosis, NC-MRI had a pooled per-patient sensitivity of 87.3% (95%CI:82.7-91.0%) and specificity of 81.6% (95%CI:75.3-86.8%), whilst DWI-MRI had a pooled sensitivity of 71.4% (95%CI:60.5-80.8%) and specificity of 97.1% (95%CI:91.9-99.4%). For lesions <2 cm, the pooled per-lesion sensitivity was 77.1% (95%CI:73.8-80.2%). For lesions >2 cm, pooled per-lesion sensitivity was 88.5% (95%CI:85.0-91.5%). CONCLUSION: Non-contrast MRI has a moderate negative LR and high specificity with acceptable sensitivity for the detection of HCC, even in patients with cirrhosis and with lesions <2 cm. Prospective trials to validate if non-contrast MRI can be used for HCC surveillance is warranted.

Endometriosis and menopausal hormone therapy impact the hysterectomy-ovarian cancer association.

OBJECTIVE: To evaluate the association between hysterectomy and ovarian cancer, and to understand how hormone therapy (HT) use and endometriosis affect this association. METHODS: We conducted a pooled analysis of self-reported data from 11 case-control studies in the Ovarian Cancer Association Consortium (OCAC). Women with (n = 5350) and without ovarian cancer (n = 7544) who never used HT or exclusively used either estrogen-only therapy (ET) or estrogen+progestin therapy (EPT) were included. Risk of invasive epithelial ovarian cancer adjusted for duration of ET and EPT use and stratified on history of endometriosis was determined using odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Overall and among women without endometriosis, there was a positive association between ovarian cancer risk and hysterectomy (OR = 1.19, 95% CI 1.09-1.31 and OR = 1.20, 95% CI 1.09-1.32, respectively), but no association upon adjusting for duration of ET and EPT use (OR = 1.04, 95% CI 0.94-1.16 and OR = 1.06, 95% CI 0.95-1.18, respectively). Among women with a history of endometriosis, there was a slight inverse association between hysterectomy and ovarian cancer risk (OR = 0.93, 95% CI 0.69-1.26), but this association became stronger and statistically significant after adjusting for duration of ET and EPT use (OR = 0.69, 95% CI 0.48-0.99). CONCLUSIONS: The hysterectomy-ovarian cancer association is complex and cannot be understood without considering duration of ET and EPT use and history of endometriosis. Failure to take these exposures into account in prior studies casts doubt on their conclusions. Overall, hysterectomy is not risk-reducing for ovarian cancer, however the inverse association among women with endometriosis warrants further investigation.

Urinary Phytoestrogen Levels Are Associated with Female Hormonal Cancers: An Analysis of NHANES Data From 1999 to 2010.

Phytoestrogens are plant-derived compounds that are structurally similar to endogenous estrogens. Studies have shown phytoestrogens to have possible health benefits although they could also act as endocrine disruptors. This is particularly relevant for estrogen-dependent cancers since estrogens increase risk of breast, endometrial, and ovarian cancer. Using data from the National Health and Nutritional Examination Survey (NHANES), we assessed the associations between urinary phytoestrogens (daidzein, equol, o-Desmethylangolensin (O-DMA), genistein, enterodiol, enterolactone) and breast, endometrial, and ovarian cancer using multivariate logistic regression with odds ratios (ORs) and 95% confidence intervals (CIs). Cancer diagnosis and other characteristics were collected via in-person questionnaires. We found women in the highest tertile for daidzein and enterodiol had over twice the odds of having breast cancer (OR = 2.51, 95% CI 1.44-4.36 for daidzein, OR = 2.78, 95% CI 1.44-5.37 for enterodiol). In addition, women in the highest tertiles for daidzein and genistein had three to four times the odds of having endometrial cancer, respectively (OR = 3.09, 95% CI 1.01-9.49 for daidzein, OR = 4.00, 95% CI 1.38-11.59 for genistein). Overall, phytoestrogens were positively associated with breast and endometrial cancer although the associations varied by phytoestrogen type. Additional studies are needed to further inform phytoestrogens' role in disease etiology.Supplemental data for this article is available online at at https://doi.org/10.1080/01635581.2021.2020304.

Selective internal radiation therapy for hepatocellular carcinoma: A 15-year multicenter Australian cohort study.

BACKGROUND AND AIM: The exact place for selective internal radiation therapy (SIRT) in the therapeutic algorithm for hepatocellular carcinoma (HCC) is debated. There are limited data on its indications, efficacy, and safety in Australia. METHODS: We performed a multicenter retrospective cohort study of patients undergoing SIRT for HCC in all Sydney hospitals between 2005 and 2019. The primary outcome was overall survival. Secondary outcomes were progression-free survival and adverse events. RESULTS: During the study period, 156 patients underwent SIRT across 10 institutions (mean age 67 years, 81% male). SIRT use progressively increased from 2005 (n = 2), peaking in 2017 (n = 42) before declining (2019: n = 21). Barcelona Clinic Liver Cancer stages at treatment were A (13%), B (33%), C (52%), and D (2%). Forty-four (28%) patients had tumor thrombus. After a median follow-up of 13.9 months, there were 117 deaths. Median overall survival was 15 months (95% confidence interval 11-19). Independent predictors of mortality on multivariable analysis were extent of liver involvement, Barcelona Clinic Liver Cancer stage, baseline ascites, alpha fetoprotein, and model for end-stage liver disease score. Median progression-free survival was 6.0 months (95% confidence interval 5.1-6.9 months). Following SIRT, 11% of patients were downstaged to curative therapy. SIRT-related complications occurred in 17%: radioembolization-induced liver disease (11%), pneumonitis (3%), gastrointestinal ulceration, and cholecystitis (1% each). Baseline ascites predicted for radioembolization-induced liver disease. CONCLUSION: We present the largest Australian SIRT cohort for HCC. We have identified several factors associated with a poor outcome following SIRT. Patients with early-stage disease had the best survival with some being downstaged to curative therapy.