Elevated risk of infection with SARS-CoV-2 Beta, Gamma, and Delta variants compared with Alpha variant in vaccinated individuals

The extent to which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) break through infection- or vaccine-induced immunity is not well understood. We analyzed 28,578 sequenced SARS-CoV-2 samples from individuals with known immune status obtained through national community testing in the Netherlands from March to August 2021. We found evidence of an increased risk of infection by the Beta (B.1.351), Gamma (P.1), or Delta (B.1.617.2) variants compared with the Alpha (B.1.1.7) variant after vaccination. No clear differences were found between vaccines. However, the effect was larger in the first 14 to 59 days after complete vaccination compared with ≥60 days. In contrast to vaccine-induced immunity, there was no increased risk for reinfection with Beta, Gamma, or Delta variants relative to the Alpha variant in individuals with infection-induced immunity.</p

Post-Operative Functional Outcomes in Early Age Onset Rectal Cancer

Background: Impairment of bowel, urogenital and fertility-related function in patients treated for rectal cancer is common. While the rate of rectal cancer in the young (&lt;50 years) is rising, there is little data on functional outcomes in this group. Methods: The REACCT international collaborative database was reviewed and data on eligible patients analysed. Inclusion criteria comprised patients with a histologically confirmed rectal cancer, &lt;50 years of age at time of diagnosis and with documented follow-up including functional outcomes. Results: A total of 1428 (n=1428) patients met the eligibility criteria and were included in the final analysis. Metastatic disease was present at diagnosis in 13%. Of these, 40% received neoadjuvant therapy and 50% adjuvant chemotherapy. The incidence of post-operative major morbidity was 10%. A defunctioning stoma was placed for 621 patients (43%); 534 of these proceeded to elective restoration of bowel continuity. The median follow-up time was 42 months. Of this cohort, a total of 415 (29%) reported persistent impairment of functional outcomes, the most frequent of which was bowel dysfunction (16%), followed by bladder dysfunction (7%), sexual dysfunction (4.5%) and infertility (1%). Conclusion: A substantial proportion of patients with early-onset rectal cancer who undergo surgery report persistent impairment of functional status. Patients should be involved in the discussion regarding their treatment options and potential impact on quality of life. Functional outcomes should be routinely recorded as part of follow up alongside oncological parameters

Quality of life after rectal cancer surgery: differences between laparoscopic and transanal total mesorectal excision

Background: Transanal total mesorectal excision (TaTME) is a safe alternative to laparoscopic TME for mid and low rectal cancer. TaTME allows improved visualization of the surgical planes and margins, and may potentially improve oncological outcomes. However, functional results after total mesorectal excision (TME) are variable and there are currently only a few published studies that include functional data related to the outcomes of TaTME. Methods: Fifty-four consecutive patients were included in this study: one group included 27 patients who underwent laparoscopic low anterior and the other included 27 patients who underwent TaTME. All patients were asked to complete five questionnaires related to quality of life (QOL) and function [EQ-5D-3L, EORTC-QLQ C30, EORTC-QLQ C29, Low Anterior Resection Syndrome score (LARS), and International Prostate Symptom Score IPSS]. All TaTME patients were operated on at The Gelderse Vallei Hospital by a single surgeon and had a follow-up of at least 6.6 months. Results: The EORTC-QLQ C30 and EQ-5D-3L questionnaires showed comparable outcomes in terms of QOL between the two groups. Almost all items evaluated by the EORTC-QLQ C29, including sexual outcomes, were similar between the two groups. One item concerning fecal incontinence, however, was scored worse for TaTME. There were no significant differences between the groups in terms of LARS symptoms or urinary function. Conclusions: Patients undergoing laparoscopic or transanal TME showed comparable functional and QOL outcomes. Although the TaTME technique is still evolving, this study indicates that this technique is a safe alternative to laparoscopic surgery in terms of functional outcomes for mid and low rectal cancers

Laparoscopic right posterior sectionectomy: single-center experience and technical aspects

Purpose: Laparoscopic right posterior sectionectomy (LRPS) is a technically demanding procedure. The aim of this article is to share our experience with LRPS and to highlight technical aspects of this procedure. Methods: This is a single-center retrospective analysis of all patients who underwent LRPS between September 2011 and October 2017. Data were retrieved from a prospectively maintained database. Video-in-picture (VIP) technology is used to facilitate and to highlight the technical aspects of this procedure. Results: In total, 18 patients underwent LRPS. Indication for surgery was mainly liver metastases (n = 11) and hepatocellular carcinoma (n = 6). The Glissonean approach for inflow control was used in 13 patients. Median operative time was 162 (140–190) minutes. Median blood loss was 325 mL (IQR: 150–450). One conversion (5.5%) was required. There were two minor complications and one major complication. Median hospital stay was 6 days (range 5–8 days). All patients had an R0 resection. There was no 90-day mortality. Conclusion: The results of our experience in LRPS add weight to the feasibility and safety of this approach

Laparoscopic right posterior sectionectomy: single-center experience and technical aspects

PURPOSE: Laparoscopic right posterior sectionectomy (LRPS) is a technically demanding procedure. The aim of this article is to share our experience with LRPS and to highlight technical aspects of this procedure. METHODS: This is a single-center retrospective analysis of all patients who underwent LRPS between September 2011 and October 2017. Data were retrieved from a prospectively maintained database. Video-in-picture (VIP) technology is used to facilitate and to highlight the technical aspects of this procedure. RESULTS: In total, 18 patients underwent LRPS. Indication for surgery was mainly liver metastases (n = 11) and hepatocellular carcinoma (n = 6). The Glissonean approach for inflow control was used in 13 patients. Median operative time was 162 (140-190) minutes. Median blood loss was 325 mL (IQR: 150-450). One conversion (5.5%) was required. There were two minor complications and one major complication. Median hospital stay was 6 days (range 5-8 days). All patients had an R0 resection. There was no 90-day mortality. CONCLUSION: The results of our experience in LRPS add weight to the feasibility and safety of this approach.status: publishe

Attenuated atrial natriuretic peptide-mediated lipolysis in subcutaneous adipocytes of obese type 2 diabetic men

Catecholamines and atrial natriuretic peptide (ANP) are major regulators of adipocyte lipolysis. Although obesity is characterized by catecholamine resistance in subcutaneous adipose tissue (SCAT), data on ANP lipolytic response and sensitivity in different adipose tissue (AT) depots of metabolically distinct humans are scarce. Ex vivo catecholamine- and ANP-induced lipolysis was investigated in adipocytes derived from SCAT and visceral AT (VAT) depot of lean (n = 13) and obese men, with (n = 11) or without (n = 18) type 2 diabetes (HbA(1c) &lt;or &gt;= 6.5%). Underlying molecular mechanisms were examined by looking at functional receptors in the NP signalling pathway at the mRNA and protein level. Maximal ANP-and catecholamine-induced lipolysis in SCAT was blunted in obese type 2 diabetics compared with age-matched lean men whereas non-diabetic obese subjects showed intermediate responses. This blunted ANP-mediated lipolytic response was accompanied by lower mRNA and protein expression of the type-A natriuretic peptide (NP) receptor and higher mRNA but reduced protein expression of the scavenging type-C receptor. Maximal ANP-induced lipolysis was lower in VAT compared with SCAT but not different between groups. Collectively, our data show that both ANP-and catecholamine-mediated lipolysis is attenuated in SCAT of obese men with type 2 diabetes, and might be partially explained by NP receptor defects. Therefore, improving maximal ANP responsiveness in adipose tissue might be a potential novel strategy to improve obesity-associated metabolic complications

Monocyte activation and disease activity in multiple sclerosis. A longitudinal analysis of serum MRP8/14 levels

In active multiple sclerosis (MS) lesions macrophages expressing myeloid related protein (MRP) 8/14 are present. The aim of this study was to determine whether serum levels of MRP8/14 complexes are related to disease activity in MS. In a longitudinal study of 16 relapsing remitting (RR) MS patients that underwent monthly gadolinium diethylentriaminepenta acid (Gd-DTPA) magnetic resonance imaging (MRI), the relation between serum MRP8/14 levels and disease activity was investigated. Patients were participating in a monoclonal antibody study targeting a specific T cell population (Vbeta5.2/5.3+ T-cells). In time, within patients large variations in serum MRP8/14 levels were observed. Serum MRP8/14 levels were not related to changes in clinical disease activity or increase in Gd-DTPA lesion enhancement. Neither did comparison of active (>1 relapse in follow-up period) with inactive (0-1 relapse) MS patients reveal any differences in MRP8/14 levels. Therefore, we conclude that although MRP8/14 expression is a good histopathological marker for monocyte activation, serum levels of these proteins do not correlate with disease activity in RR MS

CLASSICA: Validating artificial intelligence in classifying cancer in real time during surgery

&lt;p&gt;We present the Study Protocol for the &lt;a href="https://classicaproject.eu/"&gt;CLASSICA project&lt;/a&gt;.&lt;/p&gt;&lt;h2&gt;Abstract&lt;/h2&gt;&lt;h3&gt;Aim&lt;/h3&gt;&lt;p&gt;Treatment pathways for significant rectal polyps differ depending on the underlying pathology, but pre-excision profiling is imperfect. It has been demonstrated that differences in fluorescence perfusion signals following injection of indocyanine green (ICG) can be analysed mathematically and, with the assistance of artificial intelligence (AI), used to classify tumours endoscopically as benign or malignant. This study aims to validate this method of characterization across multiple clinical sites regarding its generalizability, usability and accuracy while developing clinical-grade software to enable it to become a useful method.&lt;/p&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;The CLASSICA study is a prospective, unblinded multicentre European observational study aimed to validate the use of AI analysis of ICG fluorescence for intra-operative tissue characterization. Six hundred patients undergoing transanal endoscopic evaluation of significant rectal polyps and tumours will be enrolled in at least five clinical sites across the European Union over a 4-year period. Video recordings will be analysed regarding dynamic fluorescence patterns centrally as software is developed to enable analysis with automatic classification to happen locally. AI-based classification and subsequently guided intervention will be compared with the current standard of care including biopsies, final specimen pathology and patient outcomes.&lt;/p&gt;&lt;h3&gt;Discussion&lt;/h3&gt;&lt;p&gt;CLASSICA will validate the use of AI in the analysis of ICG fluorescence for the purposes of classifying significant rectal polyps and tumours endoscopically. Follow-on studies will compare AI-guided targeted biopsy or, indeed, AI characterization alone with traditional biopsy and AI-guided local excision versus traditional excision with regard to marginal clearance and recurrence.&lt;/p&gt;&lt;p&gt;No identifiable patient data are contained in this manuscript.&lt;/p&gt;&lt;p&gt;This trial has been registered at &lt;a href="http://clinicaltrials.gov/"&gt;clinicaltrials.gov&lt;/a&gt; (Identifier NCT05793554).&lt;/p&gt;&lt;p&gt;This manuscript details version 3.5 of the protocol as approved by all clinical partners on 7 February 2023 and submitted to the relevant local ethical committees and funding body. The study protocol was written by A Moynihan (Clinical Research Fellow at UCD) under the supervision of Professor Ronan Cahill and with input from co-lead investigators at each clinical site. University College Dublin Clinical Research Centre, Ireland, is trial sponsor (contact at &lt;a href="mailto:[email protected]"&gt;[email protected]&lt;/a&gt;).&lt;/p&gt