Chemical analysis of flotsam ambergris.

The natural product ambergris is only found rarely on beaches, as jetsam. Even more scarce, or even absent, are accounts of flotsam ambergris. Here, we report the chemical analysis of a rare, large piece (>100kg) of flotsam found in the Atlantic in 2019. About 95% of subsamples from the outside of the coprolith was soluble in dichloromethane. Of this, FTIR spectroscopy, APCI-MS and GC-MS indicated the presence of ambrein. Radiocarbon dating indicated that the sample was post 1950s in age. The 13C/12C isotope ratio (-22.5 ‰) was typical of those reported to date for whale 'body' ambergris. Metals of ambergris have hardly been reported previously. The distribution found here for the flotsam, was dominated by copper and zinc, which is similar to that of several squid species. This is also consistent with the presence of squid beaks in the coprolith. Squid are a major prey species of sperm whales.

Myoferlin: a potential marker of response to radiotherapy and survival in locally advanced rectal cancer.

PURPOSE: Patients with locally advanced rectal cancer often require neo-adjuvant chemoradiotherapy to downstage the disease, but the response is variable with no predictive biomarkers. We have previously revealed through proteomic profiling that myoferlin is associated with response to radiotherapy. The aims of this study were to further validate this finding and explore the potential for myoferlin to act as a prognostic and/or therapeutic target. MATERIALS AND METHODS: Immunohistochemical analysis of a tissue microarray for 111 patients was used to validate the initial proteomic findings. Manipulation of myoferlin was achieved using siRNA, a small molecular inhibitor (wj460) and a CRISPR-Cas9 knockout cell line. Radiosensitisation following treatment was assessed using 2D clonogenic assays, 3D spheroid models and patient derived organoids. Underlying mechanisms were investigated using electrophoresis, immunofluorescence and immunoblotting. RESULTS: Analysis of both the diagnostic biopsy and tumour resection samples confirmed that low myoferlin expression correlated with a good response to neoadjuvant LCRT. High myoferlin expression was associated with spread to local lymph nodes and worse 5-year survival (p = 0.01, HR 3.5, 95%CI [1.27, 10.04]). This was externally validated using the S:CORT database. Quantification of myoferlin using immunoblotting in immortalised colorectal cancer cell lines and organoids demonstrated that high myoferlin expression was associated with increased radioresistance. Biological and pharmacological manipulation of myoferlin resulted in significantly increased radiosensitivity across all cell lines in 2D and 3D models. Following irradiation, myoferlin knockdown cells had a significantly impaired ability to repair DNA double strand breaks. This appeared to be mediated via non-homologous end-joining. CONCLUSIONS: We have confirmed that high expression of myoferlin in rectal cancer is associated with poor response to neoadjuvant therapy and worse long-term survival. Furthermore, the manipulation of myoferlin led to increased radiosensitivity in vitro. This suggests that myoferlin could be targeted to enhance the sensitivity of rectal cancer patients to radiotherapy and further work is required.

Defining Benchmarks for Pelvic Exenteration Surgery: A Multicentre Analysis of Patients with Locally Advanced and Recurrent Rectal Cancer.

OBJECTIVE: To establish globally applicable benchmark outcomes for pelvic exenteration (PE) in patients with locally advanced primary (LARC) and recurrent rectal cancer (LRRC), using outcomes achieved at highly specialised centres. BACKGROUND DATA: PE is established as the standard of care for selected patients with LARC and LRRC. There are currently no available benchmarks against which surgical performance in PE can be compared for audit and quality improvement. METHODS: This international multicentre retrospective cohort study included patients undergoing PE for LARC or LRRC at 16 highly experienced centres between 2018 and 2023. Ten outcome benchmarks were established in a lower-risk subgroup. Benchmarks were defined by the 75th percentile of the results achieved at the individual centres. RESULTS: 763 patients underwent PE, of which 464 patients (61%) had LARC and 299 (39%) had LRRC. 544 patients (71%) who met predefined lower risk criteria formed the benchmark cohort. For LARC patients, the calculated benchmark threshold for major complication rate was ≤44%; comprehensive complication index (CCI): ≤30.2; 30-day mortality rate: 0%; 90-day mortality rate: ≤4.3%; R0 resection rate: ≥79%. For LRRC patients, the calculated benchmark threshold for major complication rate was ≤53%; CCI: ≤34.1; 30-day mortality rate: 0%; 90-day mortality rate: ≤6%; R0 resection rate: ≥77%. CONCLUSIONS: The reported benchmarks for PE in patients with LARC and LRRC represent the best available care for this patient group globally and can be used for rigorous assessment of surgical quality and to facilitate quality improvement initiatives at international exenteration centres.

If speed is of the essence: rapid analysis of ambergris by APCI compact mass spectrometry.

The use of atmospheric pressure chemical ionisation (APCI) compact mass spectrometry (CMS) was investigated for the analysis of jetsam and museum-archived ambergris and of ambergris components in perfumes. The data were compared with those from existing methods. Authentic samples of some individual ambergris constituents (ambrein, coprostanol, epicoprostanol and coprostanone), were also examined. Rapid APCI CMS was achieved using either a solids probe or a probe with solutions held in capillary melting point tubes. Interpretation is made of the spectra of the principal natural product components, the relative ion responses were measured and the elemental composition of key ions in the spectra confirmed using high resolution accurate mass APCI MS. Rapid analysis of ambergris by APCI CMS may prove to be a further convenient method of identifying ambrein, of measuring the relative ratios of ambrein and steroids in ambergris and even of quantifying the latter, with minimal sample preparation.

Variation in outcome measurement and reporting in studies of pelvic exenteration for locally advanced and recurrent rectal cancer: a systematic review.

AIM: There is increasing research interest in pelvic exenteration for locally advanced and recurrent rectal cancer. Heterogeneity in outcome reporting can prevent meaningful interpretation and valid synthesis of pooled data and meta-analyses. The aim of this study was to assess homogeneity in outcome measures in the current pelvic exenteration literature. METHOD: MEDLINE, Embase, CENTRAL, CINAHL and Scopus databases were searched from 1990 to 25 April 2023 to identify studies reporting outcomes of pelvic exenteration for locally advanced or recurrent rectal cancer. All reported outcomes were extracted, merged with those of similar meaning and assigned a domain. RESULTS: Of 4137 abstracts screened, 156 studies met the inclusion criteria. A total of 2765 outcomes were reported, of which 17% were accompanied by a definition. There were 1157 unique outcomes, merged into 84 standardized outcomes and assigned one of seven domains. The most reported domains were complications (147 studies, 94%), survival (127, 81%) and surgical outcomes (123, 79%). Resection margins were reported in 122 studies (78%): the definition of a clear resection margin was not provided in 45 studies (37%), it was unclear in 11 studies (9%) and not specified beyond microscopically 'clear' or 'negative' in 31 (28%). Measurements of 2, 1, 0.5 mm and any healthy tissue were all used to define R0 margins. CONCLUSION: There is significant heterogeneity in outcome measurement and reporting in the current pelvic exenteration literature, raising concerns about the validity of comparative or collaborative studies between centres and meta-analyses. Coordinated international collaboration is required to define core outcome sets and benchmarks.

Vancomycin Graft Presoaking in Anterior Cruciate Ligament Reconstruction Surgery Is Associated with a Lower Risk of Graft Rerupture as Compared With No Vancomycin Presoaking: Systematic Review and Meta-analysis.

BACKGROUND: To determine whether there is any difference in graft rerupture rates and clinical outcomes between cases having vancomycin graft presoaking vs. no vancomycin presoaking in anterior cruciate ligament (ACL) reconstruction (ACLR). METHODS: Systematic review and meta-analysis. PubMed, Embase, CINAHL, and Cochrane CENTRAL were searched. Full published studies reporting on the relation between vancomycin graft presoaking and rates of graft rerupture and/or clinical outcomes in ACLR surgery vs. no vancomycin graft presoaking were included. Data extraction and quality appraisal were performed. Meta-analysis was conducted using a random effects model. The study's protocol was prospectively registered with PROSPERO (CRD42021290608). RESULTS: The literature search identified 907 records. After removing duplicates and those not meeting inclusion criteria, 8 studies were included. Meta-analysis showed that the estimated risk of hamstring graft rerupture was lower in cases presoaked with vancomycin vs. those having no presoaking (3.2% vs. 6.2% rerupture rate, risk ratio [RR] = 0.507, 95% CI, 0.39-0.737, p < 0.001). Similarly, the estimated risk of graft rerupture was lower in cases presoaked with vancomycin vs. those having no presoaking when the analysis included various ACL graft types (2.7% vs. 3.9% rerupture rate, RR = 0.557, 95% confidence interval [CI], 0.403-0.771, p < 0.001). Meta-analysis also showed that vancomycin graft presoaking was associated with similar International Knee Documentation Committee scores as compared with no presoaking when looking at hamstring grafts (estimated mean difference 0.112, 95% CI, -2.359 to 2.582, p = 0.929) or when considering various graft types (estimated mean difference 0.933, 95% CI, -0.140 to 2.006, p = 0.088). CONCLUSION: Vancomycin graft presoaking is a safe practice and does not compromise ACL graft rerupture rates or clinical outcomes. LEVEL OF EVIDENCE: Level IV. See Instructions for Authors for a complete description of levels of evidence.

Cementing Techniques In Knee Surgery (CeTIKS): a UK expert consensus study.

Aims: Aseptic loosening is the most common cause of failure following cemented total knee arthroplasty (TKA), and has been linked to poor cementation technique. We aimed to develop a consensus on the optimal technique for component cementation in TKA. Methods: A UK-based, three-round, online modified Delphi Expert Consensus Study was completed focusing on cementation technique in TKA. Experts were identified as having a minimum of five years' consultant experience in the NHS and fulfilling any one of the following criteria: a 'high volume' knee arthroplasty practice (> 150 TKAs per annum) as identified from the National joint Registry of England, Wales, Northern Ireland and the Isle of Man; a senior author of at least five peer reviewed articles related to TKA in the previous five years; a surgeon who is named trainer for a post-certificate of comletion of training fellowship in TKA. Results: In total, 81 experts (round 1) and 80 experts (round 2 and 3) completed the Delphi Study. Four domains with a total of 24 statements were identified. 100% consensus was reached within the cement preparation, pressurization, and cement curing domains. 90% consensus was reached within the cement application domain. Consensus was not reached with only one statement regarding the handling of cement during initial application to the tibial and/or femoral bone surfaces. Conclusion: The Cementing Techniques In Knee Surgery (CeTIKS) Delphi consensus study presents comprehensive recommendations on the optimal technique for component cementing in TKA. Expert opinion has a place in the hierarchy of evidence and, until better evidence is available these recommendations should be considered when cementing a TKA.

Development of a risk prediction tool for patients with locally advanced and recurrent rectal cancer undergoing pelvic exenteration: protocol for a mixed-methods study.

INTRODUCTION: Pelvic exenteration (PE) surgery represents the only potentially curative treatment option for patients with locally advanced or recurrent rectal cancer (LARRC). Given the potential morbidity, whether or not PE should be recommended for an individual patient presents a major decisional conflict. This study aims to identify the outcomes of PE for which there is consensus among patients, carers and clinicians regarding their importance in guiding treatment decision-making, and to develop a risk prediction tool which predicts these outcomes. METHODS AND ANALYSIS: This study will be conducted at a specialist PE centre, and employ a mixed-methods study design, divided into three distinct phases. In phase 1, outcomes of PE will be identified through a comprehensive systematic review of the literature (phase 1a), followed by exploration of the experiences of individuals who have undergone PE for LARRC and their carers (phase 1b, target sample size 10-20 patients and 5-10 carers). In phase 2, a survey of patients, their carers and clinicians will be conducted using Delphi methodology to explore consensus around the outcomes of highest priority and the level of influence each outcome should have on treatment decision-making. In phase 3 a, risk prediction tool will be developed using data from a single PE referral centre (estimated sample size 500 patients) to predict priority outcomes using multivariate modelling, and externally validated using data from an international PE collaboration. ETHICS AND DISSEMINATION: Ethical approval has been granted for phases 1 and 2 (X22-0422 and 2022/ETH02659) and for maintenance of the database used in phase 3 (X13-0283 and HREC/13/RPAH/504). Informed consent will be obtained from participants in phases 1b and 2; a waiver of consent for secondary use of data in phase 3 will be sought. Study results will be submitted for publication in international and/or national peer reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42022351909.

Patients Undergoing Systemic Anti-Cancer Therapy Who Require Surgical Intervention: What Surgeons Need to Know.

As part of routine cancer care, patients may undergo elective surgery with the aim of long-term cure. Some of these patients will receive systemic anti-cancer therapy (SACT) in the neoadjuvant and adjuvant settings. The majority of patients, usually with locally advanced or metastatic disease, will receive SACT with palliative intent. These treatment options are expanding beyond traditional chemotherapy to include targeted therapies, immunotherapy, hormone therapy, radionuclide therapy and gene therapy. During treatment, some patients will require surgical intervention on an urgent or emergency basis. This narrative review examined the evidence base for SACT-associated surgical risk and the precautions that a surgical team should consider in patients undergoing SACT.

Patient and multidisciplinary team perspectives on watch and wait in rectal cancer.

This article adopts a multidisciplinary approach, including surgery, oncology, radiology and patient perspectives, to discuss the key points of debate surrounding a watch and wait approach. In an era of shared decision-making, discussion of watch and wait as an option in the context of complete clinical response is appropriate, although it is not the gold standard treatment. Key challenges are the difficulty in assessing for a complete clinical response, prediction of recurrence and access to timely diagnostics for surveillance. Salvage surgery has good results if regrowth is detected early but does have imperfect outcomes, with only a 90% salvage rate. Good communication with patients about the risks and alternatives is essential. Patients undergoing watch and wait should ideally be enrolled in prospective registries or clinical trials.

High rate of radiolucent lines following the cemented original design of the ATTUNE total knee arthroplasty.

Aims: Loosening of components after total knee arthroplasty (TKA) can be associated with the development of radiolucent lines (RLLs). The aim of this study was to assess the rate of formation of RLLs in the cemented original design of the ATTUNE TKA and their relationship to loosening. Methods: A systematic search was undertaken using the Cochrane methodology in three online databases: MEDLINE, Embase, and CINAHL. Studies were screened against predetermined criteria, and data were extracted. Available National Joint Registries in the Network of Orthopaedic Registries of Europe were also screened. A random effects model meta-analysis was undertaken. Results: Of 263 studies, 12 were included with a total of 3,861 TKAs. Meta-analysis of ten studies showed high rates of overall tibial or femoral RLLs for the cemented original design of the ATTUNE TKA. The overall rate was 21.4% (95% confidence interval (CI) 12.7% to 33.7%) for all types of design but was higher for certain subgroups: 27.4% (95% CI 13.4% to 47.9%) for the cruciate-retaining type, and 29.9% (95% CI 15.6% to 49.6%) for the fixed-bearing type. Meta-analysis of five studies comparing the ATTUNE TKA with other implants showed a significantly higher risk of overall tibial or femoral RLLs (odds ratio (OR) 2.841 (95% CI 1.219 to 6.623); p = 0.016) for the ATTUNE. The rates of loosening or revision for loosening were lower, at 1.2% and 0.9% respectively, but the rates varied from 0% to 16.3%. The registry data did not report specifically on the original ATTUNE TKA or on revision due to loosening, but 'all-cause' five-year revision rates for the cemented ATTUNE varied from 2.6% to 5.9%. Conclusion: The original cemented ATTUNE TKA has high rates of RLLs, but their clinical significance is uncertain given the overall low associated rates of loosening and revision. However, in view of the high rates of RLLs and the variation in the rates of loosening and revision between studies and registries, close surveillance of patients who have undergone TKA with the original ATTUNE system is recommended.

COVID-19 Surveillance After Expiration of the Public Health Emergency Declaration - United States, May 11, 2023.

On January 31, 2020, the U.S. Department of Health and Human Services (HHS) declared, under Section 319 of the Public Health Service Act, a U.S. public health emergency because of the emergence of a novel virus, SARS-CoV-2.* After 13 renewals, the public health emergency will expire on May 11, 2023. Authorizations to collect certain public health data will expire on that date as well. Monitoring the impact of COVID-19 and the effectiveness of prevention and control strategies remains a public health priority, and a number of surveillance indicators have been identified to facilitate ongoing monitoring. After expiration of the public health emergency, COVID-19-associated hospital admission levels will be the primary indicator of COVID-19 trends to help guide community and personal decisions related to risk and prevention behaviors; the percentage of COVID-19-associated deaths among all reported deaths, based on provisional death certificate data, will be the primary indicator used to monitor COVID-19 mortality. Emergency department (ED) visits with a COVID-19 diagnosis and the percentage of positive SARS-CoV-2 test results, derived from an established sentinel network, will help detect early changes in trends. National genomic surveillance will continue to be used to estimate SARS-CoV-2 variant proportions; wastewater surveillance and traveler-based genomic surveillance will also continue to be used to monitor SARS-CoV-2 variants. Disease severity and hospitalization-related outcomes are monitored via sentinel surveillance and large health care databases. Monitoring of COVID-19 vaccination coverage, vaccine effectiveness (VE), and vaccine safety will also continue. Integrated strategies for surveillance of COVID-19 and other respiratory viruses can further guide prevention efforts. COVID-19-associated hospitalizations and deaths are largely preventable through receipt of updated vaccines and timely administration of therapeutics (1-4).

Fluorescence-guided surgery: comprehensive review.

BACKGROUND: Despite significant improvements in preoperative workup and surgical planning, surgeons often rely on their eyes and hands during surgery. Although this can be sufficient in some patients, intraoperative guidance is highly desirable. Near-infrared fluorescence has been advocated as a potential technique to guide surgeons during surgery. METHODS: A literature search was conducted to identify relevant articles for fluorescence-guided surgery. The literature search was performed using Medical Subject Headings on PubMed for articles in English until November 2022 and a narrative review undertaken. RESULTS: The use of invisible light, enabling real-time imaging, superior penetration depth, and the possibility to use targeted imaging agents, makes this optical imaging technique increasingly popular. Four main indications are described in this review: tissue perfusion, lymph node assessment, anatomy of vital structures, and tumour tissue imaging. Furthermore, this review provides an overview of future opportunities in the field of fluorescence-guided surgery. CONCLUSION: Fluorescence-guided surgery has proven to be a widely innovative technique applicable in many fields of surgery. The potential indications for its use are diverse and can be combined. The big challenge for the future will be in bringing experimental fluorophores and conjugates through trials and into clinical practice, as well as validation of computer visualization with large data sets. This will require collaborative surgical groups focusing on utility, efficacy, and outcomes for these techniques.

Past, Present and Future: Perspectives on an Oral History of Intellectual Disability Nursing.

Thirty-one participants engaged in this oral history research study aimed at exploring the lived experience of intellectual disability nurses and healthcare assistants' knowledge of the trajectory of intellectual disability nursing over the last 30 years in the Republic of Ireland and England. This paper documents some of these experiences offering perspectives on intellectual disability nursing and what is important for the future. Findings from Ireland consider the nature of intellectual disability services and the registered nurse in intellectual disability. Findings from England focus on opportunities and restrictions in intellectual disability nursing, shared visions, the changing context within which work took place and also the internal and external supports that impacted their roles. It is evident that intellectual disability nurses must be responsive to the changing landscape of service provision and also the requirements for contemporary new roles to meet the changing needs of people with intellectual disabilities.

Excess all-cause mortality in the USA and Europe during the COVID-19 pandemic, 2020 and 2021.

Both the USA and Europe experienced substantial excess mortality in 2020 and 2021 related to the COVID-19 pandemic. Methods used to estimate excess mortality vary, making comparisons difficult. This retrospective observational study included data on deaths from all causes occurring in the USA and 25 European countries or subnational areas participating in the network for European monitoring of excess mortality for public health action (EuroMOMO). We applied the EuroMOMO algorithm to estimate excess all-cause mortality in the USA and Europe during the first two years of the COVID-19 pandemic, 2020-2021, and compared excess mortality by age group and time periods reflecting three primary waves. During 2020-2021, the USA experienced 154.5 (95% Uncertainty Interval [UI]: 154.2-154.9) cumulative age-standardized excess all-cause deaths per 100,000 person years, compared with 110.4 (95% UI: 109.9-111.0) for the European countries. Excess all-cause mortality in the USA was higher than in Europe for nearly all age groups, with an additional 44.1 excess deaths per 100,000 person years overall from 2020-2021. If the USA had experienced an excess mortality rate similar to Europe, there would have been approximately 391 thousand (36%) fewer excess deaths in the USA.

Characterizations and comparison of low sulfur fuel oils compliant with 2020 global sulfur cap regulation for international shipping.

The International Marine Organization 2020 Global Sulfur Cap requires ships to burn fuels with <0.50% S and some countries require <0.10% S in certain Sulfur Emission Control Areas but little is known about these new types of fuels. Using both traditional GC-MS and more advanced chromatographic and mass spectrometry techniques, plus stable isotopic, δ13C and δ2H, analyses of pristane, phytane and n-alkanes, the organic components of a suite of three 0.50% S and three 0.10% S compliant fuels were characterized. Two oils were found to be near identical but all of the remaining oils could be forensically distinguished by comparison of their molecular biomarkers and by the profiles of the heterocyclic parent and alkylated homologues. Oils could also be differentiated by their δ13C and δ2H of n-alkanes and isoprenoids. This study provides important forensic data that may prove invaluable in the event of future oil spills.

Long-term surgical complications following pelvic exenteration: Operative management of the empty pelvis syndrome.

AIM: Pelvic exenteration (PE) has become the standard of care for locally advanced and recurrent rectal cancer. The high short-term morbidity reported from this procedure is well established; however, longer term complications of such radical surgery and their management have not been fully addressed. This study aimed to investigate the incidence, indications and outcomes of long-term (more than 90-day) reoperative surgery in this group of patients, with a focus on the empty pelvis syndrome (EPS). METHODS: Clinical data were extracted from a prospectively maintained database, with additional data pertaining to indications, operative details and outcomes of reoperative surgery obtained from electronic medical records. Patients were excluded if reoperative surgery was endoscopic or radiologically guided, was for the investigation or treatment of recurrent disease, or was clearly unrelated to previous surgery. RESULTS: Of 716 patients who underwent PE, 75 (11%) required 101 reoperative abdominal or perineal procedures, 52 (51%) of which were in 40 (6%) patients for complications of EPS. This group were more likely to have undergone a total PE (65% vs. 43%; P < 0.01) with either major bony (70% vs. 50%; P < 0.01) and/or nerve (40% vs. 25%; P = 0.03) resections at index exenteration. The patho-anatomy, surgical management and outcomes of these patients are described herein, considering separately complications of entero-cutaneous fistula, entero-perineal fistula, small bowel obstruction and local management of perineal wound complications. CONCLUSION: Six per cent of PE patients will require re-intervention for the management of EPS. Reliable strategies for preventing EPS remain elusive; however, surgical management is feasible with acceptable short-term outcomes with the optimum strategy to be selected on an individual patient basis.