The association of breast surgery ASPIRE: breast pain pathway rapid evaluation project - study protocol.

Background: Breast pain accounts for 20-40% of new referrals to breast units in the UK and these patients have a very low risk of breast cancer. Patients have previously been assessed in resource-intensive, cancer-exclusion, one stop clinics, which are now failing to meet government targets due to excessive demand. UK Breast units are increasingly piloting Breast Pain-only Pathways (BPP) to assess these patients, and there is no consensus for the optimal pathway. The aim of this prospective multicentre study is to assess the safety and patient satisfaction of different BPPs to inform future BPP design and implementation. Methods: All UK breast units will be invited to join the ASPIRE study between January 2023 and December 2023. Units with a BPP are invited to submit their pathway for evaluation; and those without a BPP who see patients with breast pain-only in a one stop clinics setting are also invited to join the study to evaluate the traditional pathway model concurrently. Patient satisfaction assessments will be collected after their initial consultation and patient outcomes, including subsequent cancer diagnosis, will be followed up at 12 months to determine if they have cancer diagnosis after discharge to assess pathway safety.

High wavenumber Raman spectroscopy for intraoperative assessment of breast tumour margins.

Optimal oncological results and patient outcomes are achieved in surgery for early breast cancer with breast conserving surgery (BCS) where this is appropriate. A limitation of BCS occurs when cancer is present at, or close, to the resection margin - termed a 'positive' margin - and re-excision is recommended to reduce recurrence rate. This is occurs in 17% of BCS in the UK and there is therefore a critical need for a way to assess margin status intraoperatively to ensure complete excision with adequate margins at the first operation. This study presents the potential of high wavenumber (HWN) Raman spectroscopy to address this. Freshly excised specimens from thirty patients undergoing surgery for breast cancer were measured using a surface Raman probe, and a multivariate classification model to predict normal versus tumour was developed from the data. This model achieved 77.1% sensitivity and 90.8% specificity following leave one patient out cross validation, with the defining features being differences in water content and lipid versus protein content. This demonstrates the feasibility of HWN Raman spectroscopy to facilitate future intraoperative margin assessment at specific locations. Clinical utility of the approach will require further research.

Psychology: Early print uses of the term by Pier Nicola Castellani (1525) and Gerhard Synellius (1525).

We identify the putatively earliest extant print source of the neoclassical term psychologia, long presumed to have been a 1575 work, as two 1525 works, one by Pier Nicola Castellani and another by Gerhard Synellius. We provide a history of pertinent etymology and introduce the new sources. The full paragraph containing two uses of the term by Castellani is included in translation. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Survival outcomes of elderly patients referred to the lower gastrointestinal 2-week wait service.

AIM: The benefit to elderly patients (≥80 years old) of referral to the resource-intensive lower gastrointestinal 2-week wait (LGI-2WW) pathway is unknown. The aim of this study was to investigate the survival outcome of elderly patients referred to a LGI-2WW service. METHOD: This study comprised a retrospective analysis of a prospectively gathered database of patients referred to a single-centre LGI-2WW service and conformed to STROBE guidelines. The primary outcome was all-cause mortality. Statistical analysis was performed with the chi-square test and Kaplan-Meier survival curves compared with the generalized log-rank test. RESULTS: A total of 10 155 patients referred to the LGI-2WW service between 1 January 2015 and 31 December 2018 were analysed; median follow-up was 37.0 months (range 0-66 months). Six hundred and ninety one cancers were diagnosed (6.8% detection rate); 551 (80%) of these were lower GI cancers (LGICas) [517 (75%) colorectal; 34 (5%) anal]. Forty per cent of LGICas were diagnosed via the LGI-2WW service. Patients aged ≥80 years with LGICa were more likely to be treated with palliative intent [age <80 years, 92/360 (26%) vs. age ≥80 years, 105/191 (55%); p < 0.001]. LGICa patients aged <85 years had a survival difference between those treated with curative intent (LGICa-Cur) or palliative intent (LGICa-Pal) (median survival for patients aged 80-84 years: LGICa-Cur 57 months vs. LGICa-Pal 15 months; p < 0.001). Patients aged ≥85 years did not have any survival difference by treatment intent (median survival for patients aged 85-89 years: LGICa-Cur 31 months vs. LGICa-Pal 16 months; p = 0.062; median survival for patients aged ≥90 years: LGICa-Cur 14 months vs. LGICa-Pal 16 months; p = 0.703). CONCLUSION: Patients with LGICa aged ≥85 years have similar survival whether treated with curative or palliative intent. This can inform management discussions with patients and LGI-2WW referral pathway prioritization approaches.

Noninvasive Detection of Differential Water Content Inside Biological Samples Using Deep Raman Spectroscopy.

Here we conceptually demonstrate the capability of deep Raman spectroscopy to noninvasively monitor changes in the water content within biological tissues. Water was added by injection into an isolated tissue volume (a 20 mm diameter disk of 5 mm thickness) representing a 20% increase in the overall mass, which was equivalent to a 5% increase in the water/tissue content. The elevated water content was detected through a larger volume of tissue with a total thickness of approximately 12 mm and a spiked tissue segment located in its center using transmission Raman spectroscopy (TRS) by monitoring the change of the OH (∼3390 cm-1) Raman band area (3350-3550 cm-1 spectral region) after being normalized to the neighboring CH stretching band. The tissue sample was raster scanned with TRS to yield a spatial map of the water concentration within the sample encompassing the spiked tissue zone. The mapping revealed the presence and location of the spiked region. The results provide the first conceptual demonstration using a deep Raman-based architecture, which can be used noninvasively for the detection of an elevated water content deep within biological tissues. It is envisaged that this concept could play a role in rapid in vivo detection and localization of cancerous lesions (generally exhibiting a higher water content) beneath the tissue surface.

Raman spectroscopy for rapid intra-operative margin analysis of surgically excised tumour specimens.

Raman spectroscopy, a form of vibrational spectroscopy, has the ability to provide sensitive and specific biochemical analysis of tissue. This review article provides an in-depth analysis of the suitability of different Raman spectroscopy techniques in providing intra-operative margin analysis in a range of solid tumour pathologies. Surgical excision remains the primary treatment of a number of solid organ cancers. Incomplete excision of a tumour and positive margins on histopathological analysis is associated with a worse prognosis, the need for adjuvant therapies with significant side effects and a resulting financial burden. The provision of intra-operative margin analysis of surgically excised tumour specimens would be beneficial for a number of pathologies, as there are no widely adopted and accurate methods of margin analysis, beyond histopathology. The limitations of Raman spectroscopic studies to date are discussed and future work necessary to enable translation to clinical use is identified. We conclude that, although there remain a number of challenges in translating current techniques into a clinically effective tool, studies so far demonstrate that Raman Spectroscopy has the attributes to successfully perform highly accurate intra-operative margin analysis in a clinically relevant environment.

Vertical Augmentation Mastopexy with Implant Isolation and Tension Management.

BACKGROUND: The increasingly popular vertical method of mastopexy is less commonly the technique of choice in augmentation mastopexy possibly due to concerns raised in the literature. The purpose of this report is to evaluate safety and satisfaction of the author's variation of the vertical method in this combination surgery. It includes unique tension management steps and total implant isolation from cut parenchyma. METHODS: A retrospective analysis was done of 105 consecutive patients treated with the author's method over an 8 year 6 month period. Clinical outcomes were examined, and a Breast-Q survey and Spear's 2004 survey were mailed to all patients who agreed to it by phone. RESULTS: There were no hematomas or delayed healing but one pulmonary embolus treated as an outpatient and one infection appearing 6 weeks postoperatively. There were only 3 grade 3 or 4 capsular contractures. Sixty-seven patients consented to the survey and 36 were returned. With Breast-Q, there was a mean score of 82.78 for outcome satisfaction and 75.94 for satisfaction with breasts. Spear's survey confirmed high satisfaction with 90.9% indicating that they were satisfied or extremely satisfied. Comparison with Spear's own surgical results did not reach statistical significance. CONCLUSIONS: The author's specific adaptation of vertical augmentation mastopexy appears to be very safe and successfully addresses a variety of healing, tension, and exposure concerns mentioned in the literature. Implant isolation may decrease capsular contracture rate. Both Breast-Q survey and Spear's more specific survey indicate high patient satisfaction.

Strong Short-Range Cooperativity in Hydrogen-Bond Chains.

Chains of hydrogen bonds such as those found in water and proteins are often presumed to be more stable than the sum of the individual H bonds. However, the energetics of cooperativity are complicated by solvent effects and the dynamics of intermolecular interactions, meaning that information on cooperativity typically is derived from theory or indirect structural data. Herein, we present direct measurements of energetic cooperativity in an experimental system in which the geometry and the number of H bonds in a chain were systematically controlled. Strikingly, we found that adding a second H-bond donor to form a chain can almost double the strength of the terminal H bond, while further extensions have little effect. The experimental observations add weight to computations which have suggested that strong, but short-range cooperative effects may occur in H-bond chains.

Running Memory for Clinical Handoffs: A Look at Active and Passive Processing.

OBJECTIVE: The goal of the present study was to examine the effects of domain-relevant expertise on running memory and the ability to process handoffs of information. In addition, the role of active or passive processing was examined. BACKGROUND: Currently, there is little research that addresses how individuals with different levels of expertise process information in running memory when the information is needed to perform a real-world task. METHOD: Three groups of participants differing in their level of clinical expertise (novice, intermediate, and expert) performed an abstract running memory span task and two tasks resembling real-world activities, a clinical handoff task and an air traffic control (ATC) handoff task. For all tasks, list length and the amount of information to be recalled were manipulated. RESULTS: Regarding processing strategy, all participants used passive processing for the running memory span and ATC tasks. The novices also used passive processing for the clinical task. The experts, however, appeared to use more active processing, and the intermediates fell in between. CONCLUSION: Overall, the results indicated that individuals with clinical expertise and a developed mental model rely more on active processing of incoming information for the clinical task while individuals with little or no knowledge rely on passive processing. APPLICATION: The results have implications about how training should be developed to aid less experienced personnel identify what information should be included in a handoff and what should not.

The Limit of Intramolecular H-Bonding.

Hydrogen bonds are ubiquitous interactions in molecular recognition. The energetics of such processes are governed by the competing influences of pre-organization and flexibility that are often hard to predict. Here we have measured the strength of intramolecular interactions between H-bond donor and acceptor sites separated by a variable linker. A striking distance-dependent threshold was observed in the intramolecular interaction energies. H-bonds were worth less than -1 kJ mol-1 when the interacting groups were separated by ≥6 rotating bonds, but ranged between -5 and -9 kJ mol-1 for ≤5 rotors. Thus, only very strong external H-bond acceptors were able to compete with the stronger internal H-bonds. In addition, a constant energetic penalty per rotor of ∼5-6 kJ mol-1 was observed in less strained situations where the molecule contained ≥4 rotatable bonds.

Effects of riboflavin and amotosalen photoactivation systems for pathogen inactivation of fresh-frozen plasma on fibrin clot structure.

BACKGROUND: Fresh-frozen plasma (FFP) transfusion carries a risk of viral transmission from donor to recipient. Riboflavin (Mirasol) and amotosalen (Intercept) are two pathogen inactivation (PI) methods that may enhance the safety of FFP for transfusion. Our study investigated the effects of Mirasol and Intercept treatment on fibrin formation and clot structure. STUDY DESIGN AND METHODS: FFP underwent either Mirasol or Intercept treatment, and aliquots were taken before addition of the compound, before illumination (after addition of compound only), and after treatment (addition of compound plus illumination). All samples underwent turbidimetric analysis, lysis analysis, assessment of clot permeation, and analysis by laser scanning confocal microscopy. RESULTS: After treatment, there was a decrease in optical density of the fibrin network for Mirasol and Intercept, lag time to fibrin formation was prolonged for Mirasol and lysis time for Intercept, clot permeability was significantly decreased, and clot density was increased for both. CONCLUSIONS: Our study shows that plasma treated with Mirasol and Intercept produces denser clots consisting of thinner fibers and warrants further studies to evaluate the clinical significance of these structural changes in fibrin clot formation.

Can Dispersion Forces Govern Aromatic Stacking in an Organic Solvent?

Experimental support for the dominance of van der Waals dispersion forces in aromatic stacking interactions occurring in organic solution is surprisingly limited. The size-dependence of aromatic stacking in an organic solvent was examined. The interaction energy was found to vary by about 7.5 kJ mol(-1) on going from a phenyl-phenyl to an anthracene-pyrene stack. Strikingly, the experimental data were highly correlated with dispersion energies determined using symmetry-adapted perturbation theory (SAPT), while the induction, exchange, electrostatic, and solvation energy components correlated poorly. Both the experimental data and the SAPT-dispersion energies gave high-quality correlations with the change in solvent accessible area upon complexation. Thus, the size-dependence of aromatic stacking interactions is consistent with the dominance of van der Waals dispersion forces even in the presence of a competing polarizable solvent.

Jejunal diverticulum enterolith causing perforation and upper abdominal peritonitis.

A patient presented with a 4 h history of acute onset, progressive upper abdominal pain. There was localised peritonitis, with raised inflammatory markers and lactate. CT scan showed a large calcified mass, with evidence of mesenteric twist/volvulus causing some degree of small bowel obstruction. At laparotomy, there were multiple jejunal diverticula, one of which had perforated due to a large enterolith. Resection of the affected jejunum and washout was performed and the patient recovered well. Complications of jejunal diverticula and enteroliths are reported and should be considered in patients with an acute abdomen.

Improving the surgical hot clinic.

Ambulatory care is an underdeveloped concept in the setting of emergency surgery, however it is recognised that many institutions will need to develop this service to cope with increased time and financial pressures.[1] There is increased emphasis on ambulatory care pathways for a variety of medical conditions.[2] Risk management is important in managing patients with acute abdominal pain in an outpatient setting and senior doctor support is essential. While the patient remains in the community, effective communication with the patient's primary care provider improves patient safety and satisfaction.[3] This quality improvement project identified current service provision of ambulatory care for surgical patients in the hot clinic at Croydon University Hospital with subsequent consultation with the surgical department to identify problems arising from the throughput of patients. Guidelines were then updated incorporating solutions to the identified issues which were then validated by the department of general surgery. Post intervention measurement identified a decrease in patients whose principal assessment and management was made by a senior house officer level doctor through the hot clinic patient journey from 26% to 9% (64% decrease), indicating an increase in registrar and/or consultant involvement in managing the hot clinic. The number of patients attending hot clinic that had effective discharge liaison (in the form of a formal letter) to the GP increased from 18% to 68% (250% increase). In conclusion, the introduction of updated guidelines effected a safer and more effective ambulatory hot clinic to perform closer to full capacity, providing improved patient care for the local population.

Can non-polar hydrogen atoms accept hydrogen bonds?

We examine an unusual case where a neutral hydrogen atom acts as a hydrogen-bond acceptor. The association constant between trihexylsilane and perfluoro-tert-butanol was measured as ∼0.8 M(-1) in cyclohexane. Computations and experimental NMR data are consistent with a weak, but favourable Si-H···HO interaction.

Sustained cardiovascular actions of APJ agonism during renin-angiotensin system activation and in patients with heart failure.

BACKGROUND: To assess cardiovascular actions of APJ agonism during prolonged (Pyr(1))apelin-13 infusion and renin-angiotensin system activation. METHODS AND RESULTS: Forty-eight volunteers and 12 patients with chronic stable heart failure attended a series of randomized placebo-controlled studies. Forearm blood flow, cardiac index, left ventricular dimensions, and mean arterial pressure were measured using bilateral venous occlusion plethysmography, bioimpedance cardiography, transthoracic echocardiography, and sphygmomanometry, respectively, during brief local (0.3-3.0 nmol/min) and systemic (30-300 nmol/min) or prolonged systemic (30 nmol/min) (Pyr(1))apelin-13 infusions in the presence or absence of renin-angiotensin system activation with sodium depletion or angiotensin II coinfusion. During sodium depletion and angiotensin II coinfusion, (Pyr(1))apelin-13-induced vasodilatation was preserved (P<0.02 for both). Systemic intravenous (Pyr(1))apelin-13 infusion increased cardiac index, whereas reducing mean arterial pressure and peripheral vascular resistance index (P<0.001 for all) irrespective of sodium depletion or angiotensin II (0.5 ng/kg per minute) coinfusion (P>0.05 for all). Prolonged 6-hour (Pyr(1))apelin-13 infusion caused a sustained increase in cardiac index with increased left ventricular ejection fraction in patients with chronic heart failure (ANOVA; P<0.001 for all). CONCLUSIONS: APJ agonism has sustained cardiovascular effects that are preserved in the presence of renin-angiotensin system activation or heart failure. APJ agonism may hold major promise to complement current optimal medical therapy in patients with chronic heart failure. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00901719, NCT00901888, NCT01049646, NCT01179061.

A randomized, double-blind study comparing the efficacy of selenium sulfide shampoo 1% and ciclopirox shampoo 1% as adjunctive treatments for tinea capitis in children.

Our objective was to compare the efficacy of selenium sulfide shampoo 1% and ciclopirox shampoo 1% as adjunctive treatments for tinea capitis in children. Forty children aged 1-11 years with clinically diagnosed tinea capitis were randomized to receive selenium sulfide shampoo 1% or ciclopirox shampoo 1% twice a week as adjuncts to an 8-week course of ultramicronized griseofulvin dosed at 10-12 mg/kg/day. At weeks 2, 4, and 8, subjects returned to the clinic for evaluation and scalp cultures. Subjects then returned for follow-up visits 4 weeks after completing treatment. Overall, by 8 weeks, 30 of 33 (90.9%) treated children demonstrated mycological cure. Selenium sulfide shampoo 1% and ciclopirox shampoo 1% were equally effective as adjunctive treatments for tinea capitis in children in our study.