Surgical Outcomes in Total Neoadjuvant Therapy for Rectal Cancer Versus Standard Long-course Chemoradiation: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: This systematic review and meta-analysis seeks to evaluate the impact of total neoadjuvant therapy (TNT) for rectal cancers on surgical complications and surgical pathology when compared with standard long-course chemoradiotherapy (LCRT). BACKGROUND: The oncological benefits of TNT are well published in previous meta-analyses, but there is little synthesized information on how it affects surgical outcomes. A recent study has suggested an increase in local recurrence and higher rates of breached total mesorectal excision (TME) plane in TNT patients. METHODS: This study conformed to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A search was performed in Medline (via PubMed), Cochrane databases, EMBASE and CINAHL to identify relevant randomized controlled trials (RCTs) comparing outcomes between TNT and LCRT. Meta-analyses of pooled proportions between TNT and LCRT were performed, comparing primary outcomes of surgical mortality, morbidity and all reported complications; surgical-pathology differences, namely mesorectal quality, R0 resection rates, circumferential resection margin positive rates, and sphincter preservation rates. Death and progression of disease during neoadjuvant treatment period was also compared. Risk of bias of RCTs was performed using the Cochrane risk-of-bias tool by 2 independent reviewers. RESULTS: A total of 3185 patients with rectal cancer from 11 RCTs were included in the analysis: 1607 received TNT and 1578 received LCRT, of which 1422 (TNT arm) and 1391 (LCRT arm) underwent surgical resection with curative intent. There was no significant difference in mortality [risk ratio (RR)=0.86, 95% CI: 0.13-5.52, P =0.88, I2 =52%] or major complications (RR=1.04, 95% CI: 0.86-1.26, P =0.70, I2 =0%) between TNT and LCRT. There was a significantly higher risk of breached TME in TNT group on pooled analysis (RR=1.49, 95% CI: 1.03-12.16, P =0.03, I2 =0%), and on subgroup analysis there is higher risk of breached TME in those receiving extended duration of neoadjuvant treatment (>17 weeks from start of treatment to surgery) when compared with LCRT (RR=1.61, 95% CI: 1.06-2.44, P =0.03). No difference in R0 resection rates (RR=0.85, 95% CI: 0.66-1.10, P =0.21, I2 =15%), circumferential resection margin positive rates (RR=0.87, 95% CI: 0.65-1.16, P =0.35, I2 =10%) or sphincter preservation rates (RR=1.02, 95% CI: 0.83-1.25, P =0.88, I2 =57%) were observed. There was a significantly lower risk of progression of disease to an unresectable stage during the neoadjuvant treatment period in TNT patients (RR=0.60, 95% CI: 0.39-0.92, P =0.03, I2 =18%). On subgroup analysis, it appears to favor those receiving extended duration of neoadjuvant treatment (RR=0.44, 95% CI: 0.26-0.80, P =0.002), and those receiving induction-type chemotherapy in TNT (RR=0.25, 95% CI: 0.07-0.88, P =0.03). CONCLUSIONS: TNT increases rates of breached TME which can contribute to higher local recurrence rates. TNT, however, improves systemic control by reducing early progression of disease during neoadjuvant treatment period. Further research is warranted to identify patients that will benefit from this strategy.

A Comparison of Brain-State Dynamics across Common Anesthetic Agents in Male Sprague-Dawley Rats.

Anesthesia is a powerful tool in neuroscientific research, especially in sleep research where it has the experimental advantage of allowing surgical interventions that are ethically problematic in natural sleep. Yet, while it is well documented that different anesthetic agents produce a variety of brain states, and consequently have differential effects on a multitude of neurophysiological factors, these outcomes vary based on dosages, the animal species used, and the pharmacological mechanisms specific to each anesthetic agent. Thus, our aim was to conduct a controlled comparison of spontaneous electrophysiological dynamics at a surgical plane of anesthesia under six common research anesthetics using a ubiquitous animal model, the Sprague-Dawley rat. From this direct comparison, we also evaluated which anesthetic agents may serve as pharmacological proxies for the electrophysiological features and dynamics of unconscious states such as sleep and coma. We found that at a surgical plane, pentobarbital, isoflurane and propofol all produced a continuous pattern of burst-suppression activity, which is a neurophysiological state characteristically observed during coma. In contrast, ketamine-xylazine produced synchronized, slow-oscillatory activity, similar to that observed during slow-wave sleep. Notably, both urethane and chloral hydrate produced the spontaneous, cyclical alternations between forebrain activation (REM-like) and deactivation (non-REM-like) that are similar to those observed during natural sleep. Thus, choice of anesthesia, in conjunction with continuous brain state monitoring, are critical considerations in order to avoid brain-state confounds when conducting neurophysiological experiments.

Detection of COVID-19 in a Vulvar Lesion.

As new information about coronavirus disease 2019 (COVID-19) is rapidly discovered, clinicians are better equipped to make informed decisions for their patients. While current research suggests COVID-19 viral antigen is not found in vaginal secretions, its detectability in the female lower genital tract may have clinical implications for obstetric and gynecologic care for women. We present a case of a woman at 31 weeks' gestation with simultaneous upper respiratory symptoms and vulvovaginitis. She was found to have a vulvar lesion positive for severe acute respiratory syndrome-COVID by viral swab. This case shows that COVID-19 is detectable in the vulva. This may have implications for health care workers' exposure and personal protective equipment needs. While vertical transmission has largely not been reported, the presence of detectable virus in the female lower genital tract makes this a continued possibility and area of study. KEY POINTS: · COVID-19 is detectable in the female lower genital tract.. · The detection of COVID-19 in the vulva may have implications for personal protective equipment use.. · The detection of COVID-19 in vulvovaginal lesions makes vertical transmission a continued possibility..

Exploring the Quality of Feedback in Entrustable Professional Activity Narratives Across 24 Residency Training Programs.

Background Competency-based medical education (CBME) has been implemented in many residency training programs across Canada. A key component of CBME is documentation of frequent low-stakes workplace-based assessments to track trainee progression over time. Critically, the quality of narrative feedback is imperative for trainees to accumulate a body of evidence of their progress. Suboptimal narrative feedback will challenge accurate decision-making, such as promotion to the next stage of training. Objective To explore the quality of documented feedback provided on workplace-based assessments by examining and scoring narrative comments using a published quality scoring framework. Methods We employed a retrospective cohort secondary analysis of existing data using a sample of 25% of entrustable professional activity (EPA) observations from trainee portfolios from 24 programs in one institution in Canada from July 2019 to June 2020. Statistical analyses explore the variance of scores between programs (Kruskal-Wallis rank sum test) and potential associations between program size, CBME launch year, and medical versus surgical specialties (Spearman's rho). Results Mean quality scores of 5681 narrative comments ranged from 2.0±1.2 to 3.4±1.4 out of 5 across programs. A significant and moderate difference in the quality of feedback across programs was identified (χ2=321.38, P<.001, ε2=0.06). Smaller programs and those with an earlier launch year performed better (P<.001). No significant difference was found in quality score when comparing surgical/procedural and medical programs that transitioned to CBME in this institution (P=.65). Conclusions This study illustrates the complexity of examining the quality of narrative comments provided to trainees through EPA assessments.

A multidisciplinary approach for a patient with cardiogenic shock from pulmonary embolism with concomitant impending clot in transit trapped in PFO.

Impending paradoxical embolism (IPDE) is a right heart thrombus (RHT), in times of elevated pulmonary arterial pressure, that is trapped in a patent foramen ovale (PFO) Myers et al. (2010) (3). We present a case that highlights our multidisciplinary approach in a patient with IPDE with cardiogenic shock from pulmonary embolism (PE).

Assessing the impact of telehealth implementation on postpartum outcomes for Black birthing people.

BACKGROUND: The COVID-19 pandemic led to the rapid uptake of telemedicine services, which have been shown to be potentially cost-saving and of comparable quality to in-person care for certain populations. However, there are some concerns regarding the feasibility of implementation for marginalized populations, and the impact of widespread implementation of these services on health disparities has not been well studied. OBJECTIVE: This study aimed to assess the impact of telehealth implementation on postpartum care during the COVID-19 pandemic on racial disparities in visit attendance and completion of postpartum care goals. STUDY DESIGN: In this retrospective cohort study at a single tertiary care center, differences in outcomes between all Black and non-Black patients who had scheduled postpartum visits before and after telehealth implementation for postpartum care were compared. The primary outcome was postpartum visit attendance. The secondary outcomes included postpartum depression screening, contraception selection, breastfeeding status, completion of postpartum 2-hour glucose tolerance test, and cardiology follow-up for hypertensive disorders of pregnancy. In multivariable analysis, interaction terms were used to evaluate the differential impact of telehealth implementation by race. RESULTS: Of 1579 patients meeting the inclusion criteria (780 in the preimplementation group and 799 in the postimplementation group), 995 (63%) self-identified as Black. In the preimplementation period, Black patients were less likely to attend a postpartum visit than non-Black patients (63.9% in Black patients vs 88.7% in non-Black patients; adjusted odds ratio, 0.48; 95% confidence interval, 0.29-0.79). In the postimplementation period, there was no difference in postpartum visit attendance by race (79.1% in Black patients vs 88.6% in non-Black patients; adjusted odds ratio, 0.74; 95% confidence interval, 0.45-1.21). In addition, significant differences across races in postpartum depression screening during the preimplementation period became nonsignificant in the postimplementation period. Telehealth implementation for postpartum care significantly reduced racial disparities in postpartum visit attendance (interaction P=.005). CONCLUSION: Telehealth implementation for postpartum care during the COVID-19 pandemic was associated with decreased racial disparities in postpartum visit attendance.

Protocol to evaluate sequential electronic health record-based strategies to increase genetic testing for breast and ovarian cancer risk across diverse patient populations in gynecology practices.

BACKGROUND: Germline genetic testing is recommended by the National Comprehensive Cancer Network (NCCN) for individuals including, but not limited to, those with a personal history of ovarian cancer, young-onset (< 50 years) breast cancer, and a family history of ovarian cancer or male breast cancer. Genetic testing is underused overall, and rates are consistently lower among Black and Hispanic populations. Behavioral economics-informed implementation strategies, or nudges, directed towards patients and clinicians may increase the use of this evidence-based clinical practice. METHODS: Patients meeting eligibility for germline genetic testing for breast and ovarian cancer will be identified using electronic phenotyping algorithms. A pragmatic cohort study will test three sequential strategies to promote genetic testing, two directed at patients and one directed at clinicians, deployed in the electronic health record (EHR) for patients in OB-GYN clinics across a diverse academic medical center. We will use rapid cycle approaches informed by relevant clinician and patient experiences, health equity, and behavioral economics to optimize and de-risk our strategies and methods before trial initiation. Step 1 will send patients messages through the health system patient portal. For non-responders, step 2 will reach out to patients via text message. For non-responders, Step 3 will contact patients' clinicians using a novel "pend and send" tool in the EHR. The primary implementation outcome is engagement with germline genetic testing for breast and ovarian cancer predisposition, defined as a scheduled genetic counseling appointment. Patient data collected through the EHR (e.g., race/ethnicity, geocoded address) will be examined as moderators of the impact of the strategies. DISCUSSION: This study will be one of the first to sequentially examine the effects of patient- and clinician-directed strategies informed by behavioral economics on engagement with breast and ovarian cancer genetic testing. The pragmatic and sequential design will facilitate a large and diverse patient sample, allow for the assessment of incremental gains from different implementation strategies, and permit the assessment of moderators of strategy effectiveness. The findings may help determine the impact of low-cost, highly transportable implementation strategies that can be integrated into healthcare systems to improve the use of genomic medicine. TRIAL REGISTRATION: ClinicalTrials.gov. NCT05721326. Registered February 10, 2023. https://www. CLINICALTRIALS: gov/study/NCT05721326.

Esophagectomy in a patient with double aortic arch and right descending aorta.

We herein report the case of a 57-year-old man with esophageal cancer who was found to have a double aortic arch and right-sided descending aorta. Traditional approaches such as the Ivor Lewis and McKeown were excluded because the descending aorta would obscure the surgical field, and a neck anastomosis with the conduit through the ring could result in compression. We therefore opted for a left thoracoabdominal incision, allowing excellent exposure while reserving the possibility of placing the conduit substernally.

The Language of First-Trimester Nonviable Pregnancy: Patient-Reported Preferences and Clarity.

OBJECTIVE: To document the terminology patients hear during the treatment course for a nonviable pregnancy and to ask patients their perceived clarity and preference of terminology to identify a patient-centered lexicon. METHODS: We performed a preplanned substudy survey of English-speaking participants in New York, Pennsylvania, and California at the time of enrollment in a randomized multisite trial of medical management of first-trimester early pregnancy loss. The six-item survey, administered on paper or an electronic tablet, was developed and piloted for internal and external validity. We used a visual analog scale and quantified tests of associations between participant characteristics and survey responses using risk ratios. RESULTS: We approached 155 English-speaking participants in the parent study, of whom 145 (93.5%) participated. In the process of receiving their diagnosis from a clinician, participants reported hearing the terms "miscarriage" (n=109 [75.2%]) and "early pregnancy loss" (n=73 [50.3%]) more than "early pregnancy failure" (n=31 [21.3%]) and "spontaneous abortion" (n=21 [14.4%]). The majority selected "miscarriage" (n=79 [54.5%]) followed by "early pregnancy loss" (n=49 [33.8%]) as their preferred term. In multivariable models controlling for study site, ethnicity, race, history of induced abortion, and whether the current pregnancy was planned, women indicated that "spontaneous abortion" and "early pregnancy failure" were significantly less clear than "early pregnancy loss" (53/145, adjusted risk ratio 0.12, 95% CI 0.07-0.19 and 92/145, adjusted risk ratio 0.38, 95% CI 0.24-0.61, respectively, as compared with 118/145 for "early pregnancy loss"). "Miscarriage" scored similarly to "early pregnancy loss" in clarity (119/145, adjusted risk ratio 1.05, 95% CI 0.62-1.77). CONCLUSION: The terminology used to communicate "nonviable pregnancy in the first trimester" is highly variable. In this cohort of women, most preferred the term "miscarriage" and classified both "miscarriage" and "early pregnancy loss" as clear labels for a nonviable pregnancy. Health care providers can use these terms to enhance patient-clinician communication. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02012491.

Hippocampal slow oscillation: a novel EEG state and its coordination with ongoing neocortical activity.

State-dependent EEG in the hippocampus (HPC) has traditionally been divided into two activity patterns: theta, a large-amplitude, regular oscillation with a bandwidth of 3-12 Hz, and large-amplitude irregular activity (LIA), a less regular signal with broadband characteristics. Both of these activity patterns have been linked to the memory functions subserved by the HPC. Here we describe, using extracellular field recording techniques in naturally sleeping and urethane-anesthetized rats, a novel state present during deactivated stages of sleep and anesthesia that is characterized by a prominent large-amplitude and slow frequency (< or =1 Hz) rhythm. We have called this activity the hippocampal slow oscillation (SO) because of its similarity and correspondence with the previously described neocortical SO. Almost all hippocampal units recorded exhibited differential spiking behavior during the SO as compared with other states. Although the hippocampal SO occurred in situations similar to the neocortical SO, it demonstrated some independence in its initiation, coordination, and coherence. The SO was abolished by sensory stimulation or cholinergic agonism and was enhanced by increasing anesthetic depth or muscarinic receptor antagonism. Laminar profile analyses of the SO showed a phase shift and prominent current sink-source alternations in stratum lacunosum-moleculare of CA1. This, along with correlated slow oscillatory field and multiunit activity in superficial entorhinal cortex suggests that the hippocampal SO may be coordinated with slow neocortical activity through input arriving via the temporo-ammonic pathway. This novel state may present a favorable milieu for synchronization-dependent synaptic plasticity within and between hippocampal and neocortical ensembles.

Cyclic and sleep-like spontaneous alternations of brain state under urethane anaesthesia.

BACKGROUND: Although the induction of behavioural unconsciousness during sleep and general anaesthesia has been shown to involve overlapping brain mechanisms, sleep involves cyclic fluctuations between different brain states known as active (paradoxical or rapid eye movement: REM) and quiet (slow-wave or non-REM: nREM) stages whereas commonly used general anaesthetics induce a unitary slow-wave brain state. METHODOLOGY/PRINCIPAL FINDINGS: Long-duration, multi-site forebrain field recordings were performed in urethane-anaesthetized rats. A spontaneous and rhythmic alternation of brain state between activated and deactivated electroencephalographic (EEG) patterns was observed. Individual states and their transitions resembled the REM/nREM cycle of natural sleep in their EEG components, evolution, and time frame ( approximately 11 minute period). Other physiological variables such as muscular tone, respiration rate, and cardiac frequency also covaried with forebrain state in a manner identical to sleep. The brain mechanisms of state alternations under urethane also closely overlapped those of natural sleep in their sensitivity to cholinergic pharmacological agents and dependence upon activity in the basal forebrain nuclei that are the major source of forebrain acetylcholine. Lastly, stimulation of brainstem regions thought to pace state alternations in sleep transiently disrupted state alternations under urethane. CONCLUSIONS/SIGNIFICANCE: Our results suggest that urethane promotes a condition of behavioural unconsciousness that closely mimics the full spectrum of natural sleep. The use of urethane anaesthesia as a model system will facilitate mechanistic studies into sleep-like brain states and their alternations. In addition, it could also be exploited as a tool for the discovery of new molecular targets that are designed to promote sleep without compromising state alternations.