'PartBreCon' study. A UK multicentre retrospective cohort study to assess outcomes following PARTial BREast reCONstruction with chest wall perforator flaps.

BACKGROUND: Partial breast reconstruction with a pedicled chest wall perforator flap (CWPF) enables breast conservation in a higher tumour: breast volume ratio scenario. Since there is limited evidence, this retrospective cohort study aimed to ascertain immediate (30-days) and medium-term (follow-up duration) surgical outcomes. METHODS: STROBE-compliant protocol ascertained CWPF outcomes between March 2011-March 2021. UK centres known to perform CWPF were invited to participate if they performed at least 10 cases. Data were retrospectively collected, including patient demographics, tumour and treatment characteristics, and surgical and oncological outcomes. Statistical analysis (R™) included multivariable logistic regression and sensitivity analysis. RESULTS: Across 15 centres, 507 patients with median age (54 years, IQR; 48-62), body mass index (25.4 kg/m2, IQR; 22.5-29), tumour size (26 mm, IQR; 18-35), and specimen weight (62 g, IQR; 40-92) had following flap types: LiCAP (54.1%, n = 273), MiCAP/AiCAP (19.6%, n = 99), LiCAP + LTAP (19.8%, n = 100) and TDAP (2.2%, n = 11). 30-days complication rates were in 12%: haematoma (4.3%, n = 22), wound infection (4.3%, n = 22), delayed wound healing (2.8%, n = 14) and flap loss (0.6%, n = 3; 1 full) leading to readmissions (2.6%, n = 13) and re-operations (2.6%, n = 13). Positive margins (n = 88, 17.7%) led to 15.9% (n = 79) re-excisions, including 7.5% (n = 37) at the planned 2nd of 2-stage surgery and 1.8% (n = 9) mastectomy. At median 23 months (IQR; 11-39) follow-up, there were 1.2% (n = 6) symmetrisations; recurrences: local (1%), regional/nodal (0.6%) and distant (3.2%). CONCLUSIONS: This large multicentre cohort study demonstrates acceptable complication and margin re-excision rates. CWPF extends the range of breast conservation techniques. Further studies are required for long-term oncological outcomes.

Reasons for not drinking among young adults with simultaneous alcohol and cannabis use: A latent class analysis applied to daily diary data.

Simultaneous alcohol and cannabis use (i.e., simultaneous use) is prevalent among young adults and often associated with negative consequences. Understanding reasons for not drinking (RND) may provide insight into a key intervention target for reducing negative consequences associated with simultaneous use. RND may vary on a day-to-day level, and multiple RND may be endorsed on a given day. Latent class analysis (LCA) of daily diary data is a nuanced approach that can identify complex patterns of daily RND as well as its day- and person-level covariates. The current study was a secondary data analysis of daily diary data from young adults who engaged in heavy drinking and recent simultaneous use (n = 154). We aimed to: (1) characterize daily RND, (2) use LCA to classify day-level patterns of RND, and (3) compare latent classes on same-day variables (i.e., positive and negative affect, day of the week), previous-day variables (i.e., substance use, intoxication level, consequences), and person-level characteristics (i.e., age, sex, baseline substance use frequency, simultaneous use motives). Participants completed up to 14 consecutive diaries. Multilevel LCA identified four classes of heterogeneous daily RND profiles. Daily RND classes significantly differed in terms of day of the week, previous day quantity of cannabis use, and several baseline variables (age, typical substance use, simultaneous use motives). Study findings offer preliminary support for heterogeneous RND classes among young adults engaging in simultaneous use and suggest multiple avenues for future research.

Daily Exercise and Alcohol Use Among Young Adult College Students.

The present study examined associations between exercise and alcohol use at the between- and within-person levels, including temporal sequencing and the impact of gender. Participants were 221 college students that completed an online survey and 14 daily surveys assessing their daily exercise and alcohol use. Individuals who reported higher exercise scores also consumed more alcohol, on average. On days when individuals reported consuming fewer drinks than usual, they also reported greater exercise scores. Individuals reported lower exercise scores following a day with heavier alcohol use than usual or a day with heavy episodic drinking. Exercise was unassociated with next-day alcohol use. There were mixed findings on the impact of gender. Exercise may have a more proximal influence on drinking. Exercise interventions for alcohol use could target days with higher probabilities of drinking to reduce levels of alcohol use among college students.

A prospective evaluation of the American College of Surgeons Surgical Risk Calculator as a predictor of complications for breast surgery.

BACKGROUND: The infection rates for operative management of breast cancer are often unpredictable and higher than average for a clean surgical procedure (0.8% and 28%). We aimed to assess the effectiveness of the American College of Surgeons (ACS) Surgical Risk Calculator (SRC), a preoperative scoring system to calculate the risk of surgical site infection (SSI) and serious complications following breast surgery. METHODS: Prospective risk scoring using the SRC on 213 patients in the preoperative clinic and the incidence of SSI and serious complications within 30 days postoperatively was prospectively collected. RESULTS: The overall SSI rate in our sample was 5% (n=11/210 patients). For a one-unit increase in SRC score, the odds of having SSI increased by a factor of 1.88 (95% CI 1.33 to 2.74). Odds of developing SSI were higher in patients with high Body Mass Index (OR 1.25; 95% 1.13 to 1.40) and American Society of Anesthesiologists score 3 (OR 11.54; 95% CI 2.98 to 43.65). The odds of developing an SSI were ∼19 times higher if a patient had an SRC score >3.0 versus those with an SRC score <3.0. Only 3% (n=4) of patients who had an SRC score of <3.0 experienced SSI, compared with 33% (n=7) for those with a risk score of >3.0. Out of 210 patients, 9 had serious complications (4.2%). CONCLUSIONS: ACS SRC Score of more than 3 was associated with a higher likelihood of SSI. SRC was able to predict the risk of SSI and serious complications and can be used preoperatively for identification and risk minimisation.

Brief inductions in episodic past or future thinking: effects on episodic detail and problem-solving.

Episodic specificity inductions, involving brief training in recollecting episodic details, have been shown to improve subsequent performance on tasks involving remembering the past, imagining the future and problem solving. The current study examined if specificity inductions targeting self-referential past or future episodic thinking would have dissociable effects on generating past and future episodic detail and problem solving. Sixty-three participants were randomised to either a past self-referential or future self-referential episodic induction. All participants also completed a control task. Participants randomised to the self-referential future thinking induction generated more episodic details on past and future narrative tasks compared to a control task, whereas participants randomised to a self-referential past thinking induction showed similar performance to the control task. When examining within-group performance of participants randomised to the past or future induction, we found some evidence of dissociable effects of inductions on narrative generation tasks, but not on problem solving outcomes. Our findings suggest that self-referential inductions may be useful for increasing episodic specificity, but that the temporal distance and direction of the induction matters. We discuss our results in the context of the potential clinical utility of this approach for populations vulnerable to autobiographical memory disruption.

Observational studies on the efficacy of carbamazepine and ascorbyl palmitate in managing trigeminal neuralgia.

OBJECTIVE: Ascorbyl palmitate is a fat-soluble ester of vitamin C and is used as an antioxidant food additive. While literature reports that ascorbyl palmitate can prevent exacerbation of pain and improve the quality of life of patients suffering from pain, this is not yet supported by clinical trial data. Our study aimed to investigate the effectiveness of ascorbyl palmitate in managing trigeminal neuralgia. PATIENTS AND METHODS: This study was carried out in a single-centre clinical trial in which subjects suffering from trigeminal neuralgia (N=11) were included. All patients were on carbamazepine when first included and, after washout period, received Ascorbyl palmitate. Eligible patients had the most severe trigeminal neuralgia pain in the oral cavity or pain on touching trigger zones, aged 20 years or older, were capable of proper assessment of the severity of pain and their condition, and had experienced multiple episodes of intraoral pain for at least 3 months with a pain intensity of more than 4 points on the numerical rating scale. The Brief Pain Questionnaire was used to evaluate patient's quality of life. RESULTS: A total of 11 patients were included with a mean age 55.36±10.67 years (7 males, 4 females). Most patients had compression by the superior cerebellar artery and vascular loops upon magnetic resonance examination. The mean numerical rating scale score for carbamazepine after one month was 7.9±0.56 (95% CI 7.49, 8.30). Similarly, for ascorbyl palmitate was 5.5±1.50 (95% CI 4.42, 6.57) (p<0.001). CONCLUSIONS: Ascorbyl palmitate can be used as an adjunct intervention in managing trigeminal neuralgia pain. According to the results, ascorbyl palmitate prevents frequent exacerbation of pain and improves patient quality of life.

Innovations for the future of breast surgery.

BACKGROUND: Future innovations in science and technology with an impact on multimodal breast cancer management from a surgical perspective are discussed in this narrative review. The work was undertaken in response to the Commission on the Future of Surgery project initiated by the Royal College of Surgeons of England. METHODS: Expert opinion was sought around themes of surgical de-escalation, reduction in treatment morbidities, and improving the accuracy of breast-conserving surgery in terms of margin status. There was emphasis on how the primacy of surgical excision in an era of oncoplastic and reconstructive surgery is increasingly being challenged, with more effective systemic therapies that target residual disease burden, and permit response-adapted approaches to both breast and axillary surgery. RESULTS: Technologies for intraoperative margin assessment can potentially half re-excision rates after breast-conserving surgery, and sentinel lymph node biopsy will become a therapeutic procedure for many patients with node-positive disease treated either with surgery or chemotherapy as the primary modality. Genomic profiling of tumours can aid in the selection of patients for neoadjuvant and adjuvant therapies as well as prevention strategies. Molecular subtypes are predictive of response to induction therapies and reductive approaches to surgery in the breast or axilla. CONCLUSION: Treatments are increasingly being tailored and based on improved understanding of tumour biology and relevant biomarkers to determine absolute benefit and permit delivery of cost-effective healthcare. Patient involvement is crucial for breast cancer studies to ensure relevance and outcome measures that are objective, meaningful, and patient-centred.

This article describes how future innovations in science and technology influence the management of breast cancer from a surgical perspective. This work was undertaken in response to the Commission on the Future of Surgery project initiated by the Royal College of Surgeons of England.

A study protocol for a randomised trial of adjunct computerised memory specificity training (c-MeST) for major depression in youth: targeting cognitive mechanisms to enhance usual care outcomes in mental health settings.

BACKGROUND: Youth depression is highly prevalent and is related to impairments in academic, social and behavioural functioning. Evidence-based treatments are available, but many young people do not respond or sufficiently recover with first-line options, and a significant proportion experience relapse. Consequently, there is clear scope to enhance intervention in this critical period of early-onset depression. Memory specificity training (MeST) is a low-intensity intervention for depression that targets reduced specificity when recalling memories of the past, a common cognitive vulnerability in depression. This randomised controlled trial will assess the efficacy of adding a computerised version of MeST (c-MeST) to usual care for youth depression. METHODS/DESIGN: Young people aged 15-25 years with a major depressive episode (MDE) will be recruited and randomised to have immediate access to the seven session online c-MeST program in addition to usual care, or to usual care and wait-list for c-MeST. The primary outcomes will be diagnostic status of an MDE and self-reported depressive symptoms assessed at baseline, 1-, 3- and 6-month intervals. Autobiographical memory specificity and other variables thought to contribute to the maintenance of reduced memory specificity and depression will be assessed as mediators of change. DISCUSSION: Online provision of c-MeST provides a simple, low-intensity option for targeting a cognitive vulnerability that predicts the persistence of depressive symptoms. If found to be efficacious as an adjunct to usual care for depressed youth, it could be suitable for broader roll-out, as c-MeST is highly accessible and implementation requires only minimal resources due to the online and automated nature of intervention. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12619000234112p. Registered on the 18 February 2019. All items from the WHO Trial Registration Data Set can be found within the protocol. PROTOCOL VERSION: 1.0.

Cytomegalovirus Infection and Rates of Antiviral Resistance Following Intestinal and Multivisceral Transplantation.

BACKGROUND: Cytomegalovirus (CMV) disease is a common and clinically significant complication following intestinal or multivisceral transplantation. CMV disease is more common in cases of serologic mismatch between donor and recipient. Though in some cases it may be asymptomatic, in the immunosuppressed population it often manifests with evidence of systemic infection or end-organ disease. METHODS: We conducted a retrospective review of all patients undergoing intestinal or multivisceral transplantation over 8 years at our institution. RESULTS: Forty-eight transplantations were performed, with 40% of the patients (19/48) having ≥1 episode of CMV viremia, which rose to 90% in the "donor-positive, recipient-negative" (DPRN) serologic mismatch group. The median time to 1st episode following transplantation was 22.3 weeks (range, 1-78) and median duration of each episode was 4.9 weeks (range, 1.6-37.4). Six of the 19 viremic patients (31.6%) developed virologic resistance with 4 of these occurring in the DPRN group. Four of the 6 patients with drug-resistant CMV died with CMV viremia. All patients with drug resistance acquired ganciclovir resistance; these patients were more challenging to manage with second-line toxicity-limited treatments, including foscarnet, cidofovir, and leflunomide. CMV immunoglobulin has been used and we briefly discuss the use of CMV-specific adoptive T-lymphocyte transfer in the management of 1 case. CONCLUSIONS: Post-transplantation CMV disease continues to be challenging to manage, and there is little consensus on optimal management strategies in this patient group, with a significant requirement for novel therapies; these may be pharmacologic or cell based. Extensive multidisciplinary discussion is important for most cases, but particularly for those patients who acquire virologic resistance.

Impaired sodium-evoked paraventricular nucleus neuronal activation and blood pressure regulation in conscious Sprague-Dawley rats lacking central Gαi2 proteins.

AIM: We determined the role of brain Gαi2 proteins in mediating the neural and humoral responses of conscious male Sprague-Dawley rats to acute peripheral sodium challenge. METHODS: Rats pre-treated (24-h) intracerebroventricularly with a targeted oligodeoxynucleotide (ODN) (25 µg per 5 µL) to downregulate brain Gαi2 protein expression or a scrambled (SCR) control ODN were challenged with an acute sodium load (intravenous bolus 3 m NaCl; 0.14 mL per 100 g), and cardiovascular parameters were monitored for 120 min. In additional groups, hypothalamic paraventricular nucleus (PVN) Fos immunoreactivity was examined at baseline, 40, and 100 min post-sodium challenge. RESULTS: In response to intravenous hypertonic saline (HS), no difference was observed in peak change in mean arterial pressure between groups. In SCR ODN pre-treated rats, arterial pressure returned to baseline by 100 min, while it remained elevated in Gαi2 ODN pre-treated rats (P < 0.05). No difference between groups was observed in sodium-evoked increases in Fos-positive magnocellular neurons or vasopressin release. V1a receptor antagonism failed to block the prolonged elevation of arterial pressure in Gαi2 ODN pre-treated rats. A significantly greater number of Fos-positive ventrolateral parvocellular, lateral parvocellular, and medial parvocellular neurons were observed in SCR vs. Gαi2 ODN pre-treated rats at 40 and 100 min post-HS challenge (P < 0.05). In SCR, but not Gαi2 ODN pre-treated rats, HS evoked suppression of plasma norepinephrine (P < 0.05). CONCLUSION: This highlights Gαi2 protein signal transduction as a novel central mechanism acting to differentially influence PVN parvocellular neuronal activation, sympathetic outflow, and arterial pressure in response to acute HS, independently of actions on magnocellular neurons and vasopressin release.