Diagnostic accuracy of prenatal ultrasound in coarctation of aorta: systematic review and individual participant data meta-analysis.

OBJECTIVE: To determine the diagnostic accuracy of prenatal ultrasound in detecting coarctation of the aorta (CoA). METHODS: An individual participant data meta-analysis was performed to report on the strength of association and diagnostic accuracy of different ultrasound signs in detecting CoA prenatally. MEDLINE, EMBASE and CINAHL were searched for studies published between January 2000 and November 2021. Inclusion criteria were fetuses with suspected isolated CoA, defined as ventricular and/or great vessel disproportion with right dominance on ultrasound assessment. Individual participant-level data were obtained by two leading teams. PRISMA-IPD and PRISMA-DTA guidelines were used for extracting data, and the QUADAS-2 tool was used for assessing quality and applicability. The reference standard was CoA, defined as narrowing of the aortic arch, diagnosed after birth. The most commonly evaluated parameters on ultrasound, both in B-mode and on Doppler, constituted the index test. Summary estimates of sensitivity, specificity, diagnostic odds ratio (DOR) and likelihood ratios were computed using the hierarchical summary receiver-operating-characteristics model. RESULTS: The initial search yielded 72 studies, of which 25 met the inclusion criteria. Seventeen studies (640 fetuses) were included. On random-effects logistic regression analysis, tricuspid valve/mitral valve diameter ratio > 1.4 and > 1.6, aortic isthmus/arterial duct diameter ratio < 0.7, hypoplastic aortic arch (all P < 0.001), aortic isthmus diameter Z-score of < -2 in the sagittal (P = 0.003) and three-vessel-and-trachea (P < 0.001) views, pulmonary artery/ascending aorta diameter ratio > 1.4 (P = 0.048) and bidirectional flow at the foramen ovale (P = 0.012) were independently associated with CoA. Redundant foramen ovale was inversely associated with CoA (P = 0.037). Regarding diagnostic accuracy, tricuspid valve/mitral valve diameter ratio > 1.4 had a sensitivity of 72.6% (95% CI, 48.2-88.3%), specificity of 65.4% (95% CI, 46.9-80.2%) and DOR of 5.02 (95% CI, 1.82-13.9). The sensitivity and specificity values were, respectively, 75.0% (95% CI, 61.1-86.0%) and 39.7% (95% CI, 27.0-53.4%) for pulmonary artery/ascending aorta diameter ratio > 1.4, 47.8% (95% CI, 14.6-83.0%) and 87.6% (95% CI, 27.3-99.3%) for aortic isthmus diameter Z-score of < -2 in the sagittal view and 74.1% (95% CI, 58.0-85.6%) and 62.0% (95% CI, 41.6-78.9%) for aortic isthmus diameter Z-score of < -2 in the three-vessel-and-trachea view. Hypoplastic aortic arch had a sensitivity of 70.0% (95% CI, 42.0-88.6%), specificity of 91.3% (95% CI, 78.6-96.8%) and DOR of 24.9 (95% CI, 6.18-100). The diagnostic yield of prenatal ultrasound in detecting CoA did not change significantly when considering multiple categorical parameters. Five of the 11 evaluated continuous parameters were independently associated with CoA (all P < 0.001) but all had low-to-moderate diagnostic yield. CONCLUSIONS: Several prenatal ultrasound parameters are associated with an increased risk for postnatal CoA. However, diagnostic accuracy is only moderate, even when combinations of parameters are considered. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

The Potential Antidepressant Compound Org 34167 Modulates HCN Channels Via a Novel Mode of Action.

Org 34167 is a small molecule hyperpolarization-activated cyclic nucleotide-gated (HCN) channel modulator that has been trialed in humans for its potential antidepressant activity. The precise action of Org 34167 is not fully understood. Here we use two-electrode voltage clamp recordings and an allosteric model to explore the interaction of Org 34167 with human HCN1 channels. The impact of Org 34167 on channel function included a hyperpolarizing shift in activation voltage dependence and a slowing of activation kinetics. Furthermore, a reduction in the maximum open probability at extreme hyperpolarization argued for an additional voltage-independent mechanism. Org 34167 had a similar impact on a truncated HCN1 channel lacking the C-terminal nucleotide binding domain, thus ruling out an interaction with this domain. Fitting a gating model, derived from a 10-state allosteric scheme, predicted that Org 34167 strongly reduced the equilibrium constant for the voltage-independent pore domain to favor a closed pore, as well as reducing the voltage sensing domain-pore domain coupling and shifting the zero voltage equilibrium constant of the voltage sensing domain to favor the inactive state. SIGNIFICANCE STATEMENT: The brain penetrant small molecule Org 34167 has been reported to have an antidepressant action by targeting HCN channels; however, its mode of action is unknown. We used heterologously expressed human HCN1 channels to show that Org 34167 inhibits channel activity by modulating kinetic parameters associated with the channel pore domain, voltage sensing domain, and interdomain coupling.

Accelerated rehabilitation following thumb ulnar collateral ligament repair with suture tape augmentation: A case series of professional basketball players.

STUDY DESIGN: Case series. INTRODUCTION: Rehabilitation protocols following thumb metacarpophalangeal (MCP) ulnar collateral ligament (UCL) repair typically do not allow for return to sport until 12 weeks post-surgery. The potential for accelerated rehabilitation following thumb MCP UCL repair with suture tape augmentation has yet to be explored. PURPOSE OF THE STUDY: To describe the accelerated rehabilitation following thumb MCP UCL repair with the suture tape augmentation in professional basketball players. METHODS: Three professional basketball players underwent thumb MCP UCL repair with suture tape augmentation. The athletes followed an accelerated rehabilitation program post-surgery that began with range-of-motion exercises at 2-3 days, proximal strengthening at 7-10 days, grip/pinch strengthening at 1-2 weeks, followed by progressive sport specific intervention with a custom orthosis. RESULTS: At 5-6 weeks post-surgery, active thumb MCP range of motion returned to 83%-100%, grip strength to 81%-100%, and tripod pinch strength to 73%-78% of the contralateral side. All athletes successfully returned to sport within 5-6 weeks post-surgery. DISCUSSION/CONCLUSION: This is the first clinical application of an accelerated rehabilitation protocol in athletes following thumb MCP UCL repair. In this series, professional basketball players were able to return to sport in half the routine recovery time. Further prospective studies re-thinking current rehabilitation protocols are warranted.

Evaluation of the Warrior Programme intervention among UK ex-service personnel.

BACKGROUND: Research has shown that of the myriad services available to veterans in the UK, very few have been independently evaluated. This report presents the results of a randomized controlled trial assessing the impact of Time Line Therapy™ delivered by the Warrior Programme (a third-sector organization). AIMS: This study was aimed to determine if the intervention is effective in reducing emotional and functional difficulties in ex-service personnel. METHODS: A mixed-design analysis of variance model was used to investigate whether the Warrior Programme had a statistically significant impact on self-reported scores. The intervention and control group provided data on measures prior to and immediately after the intervention, and at 3-month follow-up. RESULTS: Those in the intervention group (n = 23) reported statistically significant improvements in self-reported scores immediately following intervention: the Clinical Outcomes in Routine Evaluation (CORE) scores (CORE global distress mean difference [MD] = 45.0, 95% confidence interval [CI] 31-60) (CORE subjective well-being MD = 5.9, 95% CI 3.5-8.3) (CORE functioning MD = 16.7, 95% CI 11.4-21.9) (CORE problems/symptoms MD = 19.4, 95% CI 13.1-25.7), general self-efficacy (MD = -9.8, 95% CI -13.6 to -6.8), anxiety (MD = 8.6, 95% CI 5.2-12.1), depression (MD = 10, 95% CI 6.6-13.5), post-traumatic stress disorder (MD = 26.3, 95% CI 17-25) and functional impairment (MD = 11.1, 95% CI 5.3-16.8) over time, compared to the control group (n = 29). However, score improvement was not sustained over time or statistically significant at follow-up. CONCLUSIONS: The Warrior Programme was effective in reducing emotional and functional difficulties in ex-service personnel immediately after the intervention, but the effect was not sustained at 3-month follow-up.

Good mid- to long-term results of the cemented oxford phase 3 unicompartmental knee arthroplasty in a non-designer centre.

PURPOSE: Unicompartmental knee arthroplasty (UKA) provides patients with an alternative treatment to TKA in isolated medial compartment osteoarthritis providing better functional outcomes and faster recovery in the short term. Our aim was to quantify revision rates, predictors of revision, mortality rate and functionality of the Oxford Phase 3 UKA in a non-designer institution. METHODS: This was a retrospective review of prospectively collected regional registry data. All Oxford Phase 3 UKAs performed for medial tibio-femoral osteoarthritis of the knee joint were included from a single academic institution between the period of January 1st 2006 and December 30th 2009. Kaplan-Meier survivorship curves adjusting for loss to follow-up and deceased patients were generated. Primary outcome variables included all-cause and aseptic revision. Secondary outcome variables included functional outcome scores. Patients were reviewed at 6 months, 2 years, 5 years, 10 years and 15 years. RESULTS: A total of 64 cemented Oxford phase 3 UKAs were performed between January 2006 and November 2009. Fifteen-year follow-up data were available for 51 patients, of these 12 required revision. Survival rates, adjusting for patients that were either lost to follow-up or deceased, were 87.5% at 5 years, 81.4% at 10 years and 76.4% at 15 years. The overall aseptic revision rate at the time of review was 18.75% (n = 12). The only significant predictor of postoperative WOMAC score at 15 years was the preoperative WOMAC score (p = 0.03). CONCLUSION: The Oxford Phase 3 UKA for medial tibio-femoral arthritis has promising outcomes at 15-year follow-up with a survival rate of 76.4% in a non-designer centre. LEVEL OF EVIDENCE: III.

Changing patterns of referral into a family history clinic and detection of ovarian cancer: a retrospective 10-year review.

This study examines whether a change in the criteria for genetic testing for ovarian cancer risk changed the nature of referrals into our Familial Cancer service. This is a retrospective review of 273 women who underwent risk reducing surgery (RRS). The primary outcome was to establish whether there was an increase in women having RRS with a confirmed genetic mutation. Secondary outcomes included the incidence of occult cancer and of subsequent primary peritoneal cancer. The results showed an increase in women being offered RRS based on genetic diagnosis; 91% versus 32% before the criteria change. Four occult malignancies (1.5%) and two peritoneal cancers (0.7%) were noted.We have demonstrated a change in the nature of referrals to the familial cancer service from perceived risk to genetic diagnosis. We can now counsel women more accurately. With a defined risk we are enabling them to make an informed decision regarding risk reduction.

Neoadjuvant chemoradiotherapy or chemotherapy alone for oesophageal cancer: population-based cohort study.

BACKGROUND: Although both neoadjuvant chemoradiotherapy (nCRT) and chemotherapy (nCT) are used as neoadjuvant treatment for oesophageal cancer, it is unknown whether one provides a survival advantage over the other, particularly with respect to histological subtype. This study aimed to compare prognosis after nCRT and nCT in patients undergoing oesophagectomy for oesophageal adenocarcinoma (OAC) or squamous cell carcinoma (OSCC). METHODS: Data from the National Cancer Database (2006-2015) were used to identify patients with OAC and OSCC. Propensity score matching and Cox multivariable analyses were used to account for treatment selection biases. RESULTS: The study included 11 167 patients with OAC (nCRT 9972, 89.3 per cent; nCT 1195, 10.7 per cent) and 2367 with OSCC (nCRT 2155, 91.0 per cent; nCT 212, 9.0 per cent). In the matched OAC cohort, nCRT provided higher rates of complete pathological response (35.1 versus 21.0 per cent; P < 0.001) and margin-negative resections (90.1 versus 85.9 per cent; P < 0.001). However, patients who had nCRT had similar survival to those who received nCT (hazard ratio (HR) 1.04, 95 per cent c.i. 0.95 to 1.14). Five-year survival rates for patients who had nCRT and nCT were 36 and 37 per cent respectively (P = 0.123). For OSCC, nCRT had higher rates of complete pathological response (50.9 versus 30.4 per cent; P < 0.001) and margin-negative resections (92.8 versus 82.4 per cent; P < 0.001). A statistically significant overall survival benefit was evident for nCRT (HR 0.78, 0.62 to 0.97). Five-year survival rates for patients who had nCRT and nCT were 45.0 and 38.0 per cent respectively (P = 0.026). CONCLUSION: Despite pathological benefits, including primary tumour response to nCRT, there was no prognostic benefit of nCRT compared with nCT for OAC suggesting that these two modalities are equally acceptable. However, for OSCC, nCRT followed by surgery appears to remain the optimal treatment approach.

Comparison of multimodal analgesia with thoracic epidural after transthoracic oesophagectomy.

BACKGROUND: Thoracic epidural analgesia (TEA) has been regarded as the standard of care after oesophagectomy for pain control, but has several side-effects. Multimodal (intrathecal diamorphine, paravertebral and rectus sheath catheters) analgesia (MA) may facilitate postoperative mobilization by reducing hypotensive episodes and the need for vasopressors, but uncertainty exists about whether it provides comparable analgesia. This study aimed to determine whether MA provides comparable analgesia to TEA following transthoracic oesophagectomy. METHODS: Consecutive patients undergoing oesophagectomy for cancer between January 2015 and December 2018 were grouped according to postoperative analgesia regimen. Propensity score matching (PSM) was used to account for treatment selection bias. Pain scores at rest and on movement, graded from 0 to 10, were used. The incidence of hypotensive episodes and the requirement for vasopressors were evaluated. RESULTS: The study included 293 patients; 142 (48.5 per cent) received TEA and 151 (51.5 per cent) MA. After PSM, 100 patients remained in each group. Mean pain scores were significantly higher at rest in the MA group (day 1: 1.5 versus 0.8 in the TEA group, P = 0.017; day 2: 1.7 versus 0.9 respectively, P = 0.014; day 3: 1.2 versus 0.6, P = 0.047). Fewer patients receiving MA had a hypotensive episode (25 per cent versus 45 per cent in the TEA group; P = 0.003) and fewer required vasopressors (36 versus 53 per cent respectively; P = 0.016). There was no significant difference in the overall complication rate (71.0 versus 61.0 per cent; P = 0.136). CONCLUSION: MA is less effective than TEA at controlling pain, but this difference may not be clinically significant. However, fewer patients experienced hypotension or required vasopressor support with MA; this may be beneficial within an enhanced recovery programme.

A large outbreak of measles in the West Midlands, England, 2017-2018: descriptive epidemiology, control measures and lessons learnt.

In November 2017, eight confirmed measles cases were reported to Public Health England from a hospital in the West Midlands. A multidisciplinary Incident Management Team (IMT) was established to determine the extent of the problem and coordinate an outbreak response. Between 1 November 2017 and 4 June 2018, a total of 116 confirmed and 21 likely measles cases were linked to this outbreak; just under half (43%) were aged over 15 years of age. Fifty-five of the confirmed cases were hospitalised (48%) and no deaths were reported. At the start of the outbreak, cases were mostly individuals of Romanian origin; the outbreak subsequently spread to the wider population. Over the 8-month response, the IMT conducted the following control measures: extensive contact tracing, immediate provision of post-exposure prophylaxis, community engagement amongst specific high-risk groups, MMR awareness raising including catch-up campaigns and enhanced vaccination services at selected GP surgeries. Key challenges to the effective control measures included language difficulties limiting community engagement; delays in diagnosis, notification and appropriate isolation of cases; limited resources for contact tracing across multiple high-risk settings (including GPs and hospitals) and lack of timely data on vaccine coverage in sub-groups of the population to guide public health action.

Slack as a virtual undergraduate dermatology community: a pilot study.

BACKGROUND: Dermatology is under-represented in UK undergraduate curricula, and with a diagnostic and educational toolkit that is heavily centred on face-to-face (F2F) clinical examination, dermatology education has been disproportionately affected by the COVID-19 pandemic. Online channel-based messaging apps such as Slack offer an opportunity to engage students in remote, multimodal collaborative learning by reproducing a classroom environment in the virtual space. AIM: To determine the feasibility, acceptability and proof of concept for an online Slack community in undergraduate dermatology education. METHODS: Undergraduate medical students participated in an online classroom for a 6-week programme encompassing case-based discussions, seminars and journal clubs. The platform was facilitated by junior doctors (n = 10) and patient educators (n = 6). Students and faculty completed a post-course evaluation. Students additionally completed a pre- and post-intervention dermatology quiz. Mixed methods analyses included quantitative analyses to explore data trends and qualitative phenomenographic analyses to assimilate key underlying themes. RESULTS: Students (n = 65) were enrolled to join the platform. The evaluation was completed by students (n = 52) from UK universities (n = 27). The majority of students (n = 27) interacted with the platform as passive observers (≤ 5 active interactions with the channel), with a small group (n = 4) of 'super-users' (≥ 100 active interactions). The overall quality of the course was described as 'excellent' by 96% of participants and 100% of faculty. CONCLUSION: A community-based online classroom can act as an enjoyable, acceptable and collaborative means of delivering dermatology education to undergraduate medical students. Its ease of use and supportive nature may also facilitate patient involvement. Such advances may provide vital safeguards against the reduction in F2F learning that has accompanied the COVID-19 pandemic.

Prehabilitation, improving postoperative outcomes.

Cardiopulmonary fitness impacts upon post-operative outcomes. Improved fitness may lead to a reduction in postoperative morbidity, mortality, reduced length of stay and improvements in patients quality of life. Prehabilitation can be defined as a group of interventions undertaken prior to a surgical procedure, with the aim of reducing peri-operative risk, improving post-operative recovery and outcomes. This is an evolving field which is generating significant scientific and clinical interest. There is growing evidence demonstrating the effectiveness of this approach. It has been proven that prehabilitation could lead to improvement in cardiopulmonary fitness and reduction of postoperative morbidity. Physical exercise composed of aerobic and strengthening exercise is a mainstay of prehabilitation. Multimodal interventions are preferred nowadays and therefore these programmes are commonly enhanced by nutritional and psychological support. Prehabilitation has its place in elective surgery and should be commenced immediately after diagnosis is made. It can be home-based or within hospitals under supervision. Prehabilitation programmes should be individualised, based on patients diagnosis, age, comorbidities, background physical activity and social circumstances in order to achieve the highest possible effectivity of the programmes. It remains unclear as to what the optimal programme looks like in terms of frequency, length and intensity of exercise. High-intensity interval training has been shown to be highly effective. There is a need to answer many questions and bring more substantial evidence of prehabilitation effectivity before this can become part of a routine clinical care. There are several ongoing large randomised clinical in prehabilitation that can help address this knowledge gap.

Evaluating species in Botryosphaeriales.

The Botryosphaeriales (Dothideomycetes) includes numerous endophytic, saprobic, and plant pathogenic species associated with a wide range of symptoms, most commonly on woody plants. In a recent phylogenetic treatment of 499 isolates in the culture collection (CBS) of the Westerdijk Institute, we evaluated the families and genera accommodated in this order of important fungi. The present study presents multigene phylogenetic analyses for an additional 230 isolates, using ITS, tef1, tub2, LSU and rpb2 loci, in combination with morphological data. Based on these data, 58 species are reduced to synonymy, and eight novel species are described. They include Diplodia afrocarpi (Afrocarpus, South Africa), Dothiorella diospyricola (Diospyros, South Africa), Lasiodiplodia acaciae (Acacia, Indonesia), Neofusicoccum podocarpi (Podocarpus, South Africa), N. rapaneae (Rapanea, South Africa), Phaeobotryon ulmi (Ulmus, Germany), Saccharata grevilleae (Grevillea, Australia) and S. hakeiphila (Hakea, Australia). The results have clarified the identity of numerous isolates that lacked Latin binomials or had been deposited under incorrect names in the CBS collection in the past. They also provide a solid foundation for more in-depth future studies on taxa in the order. Sequences of the tef1, tub2 and rpb2 genes proved to be the most reliable markers. At the species level, results showed that the most informative genes were inconsistent, but that a combination of four candidate barcodes (ITS, tef1, tub2 and rpb2) provided reliable resolution. Furthermore, given the large number of additional isolates included in this study, and newly generated multigene DNA datasets, several species could also be reduced to synonymy. The study illustrates the value of reassessing the identity of older collections in culture collections utilising modern taxonomic frameworks and methods. Citation: Zhang W, Groenewald JZ, Lombard L, et al. 2021. Evaluating species in Botryosphaeriales. Persoonia 46: 63-115. https://doi.org/10.3767/persoonia.2021.46.03.

Sexual risk and HIV testing disconnect in men who have sex with men (MSM) recruited to an online HIV self-testing trial.

OBJECTIVES: We report the frequency of previous HIV testing at baseline in men who have sex with men (MSM) who enrolled in an HIV self-testing (HIVST) randomized controlled trial [an HIV self-testing public health intervention (SELPHI)]. METHODS: Criteria for enrolment were age ≥ 16 years, being a man (including trans men) who ever had anal intercourse (AI) with a man, not being known to be HIV positive and having consented to national HIV database linkage. Using online survey baseline data (2017-2018), we assessed associations with never having tested for HIV and not testing in the previous 6 months, among men who reported at least two recent condomless AI (CAI) partners. RESULTS: A total of 10 111 men were randomized; the median age was 33 years [interquartile range (IQR) 26-44 years], 89% were white, 20% were born outside the UK, 0.8% were trans men, 47% were degree educated, and 8% and 4% had ever used and were currently using pre-exposure prophylaxis (PrEP), respectively. In the previous 3 months, 89% reported AI and 72% reported CAI with at least one male partner. Overall, 17%, 33%, 54%, and 72% had tested for HIV in the last 3 months, 6 months, 12 months and 2 years, respectively; 13% had tested more than 2 years ago and 15% had never tested. Among 3972 men reporting at least two recent CAI partners, only 22% had tested in the previous 3 months. Region of residence and education level were independently associated with recent HIV testing. Among current PrEP users, 15% had not tested in the previous 6 months. CONCLUSIONS: Most men in SELPHI, particularly those reporting at least two CAI partners and current PrEP users, were not testing in line with current UK recommendations. The results of the trial will inform whether online promotion of HIVST addresses ongoing testing barriers.

HIV self-testing intervention experiences and kit usability: results from a qualitative study among men who have sex with men in the SELPHI (Self-Testing Public Health Intervention) randomized controlled trial in England and Wales.

OBJECTIVES: SELPHI (HIV Self-Testing Public Health Intervention) is the largest randomized controlled trial (RCT) of HIV self-testing (HIVST) in a high-income setting to date, and has recruited 10 000 men who have sex with men (cis- and transgender) and transgender women who have sex with men. This qualitative substudy aimed to explore how those utilizing self-tests experience HIVST and the implications for further intervention development and scale-up. This is the first qualitative study in Europe investigating experiences of HIVST among intervention users, and the first globally examining the experience of using blood-based HIVST. METHODS: Thirty-seven cisgender MSM SELPHI participants from across England and Wales were purposively recruited to the substudy, in which semi-structured interviews were used to explore testing history, HIVST experiences and intervention preferences. Interviews were audio-recorded, transcribed and analysed through a framework analysis. RESULTS: Men accessed the intervention because HIVST reduced barriers related to convenience, stigma and privacy concerns. Emotional responses had direct links to acceptability. Supportive intervention components increased engagement with testing and addressed supportive concerns. HIVST facilitated more frequent testing, with the potential to reduce sexually transmitted infection (STI) screening frequency. Substudy participants with an HIV-positive result (n = 2) linked to care promptly and reported very high acceptability. Minor adverse outcomes (n = 2; relationship discord and fainting) did not reduce acceptability. Ease of use difficulties were with the lancet and the test processing stage. CONCLUSIONS: Intervention components shaped acceptability, particularly in relation to overcoming a perceived lack of support. The intervention was broadly acceptable and usable; participants expressed an unexpected degree of enthusiasm for HIVST, including those with HIV-positive results and individuals with minor adverse outcomes.

The EuroSIDA study: 25 years of scientific achievements.

The EuroSIDA study was initiated in 1994 and follows adult people living with HIV (PLHIV) in 100 collaborating clinics across 35 countries covering all European regions, Israel and Argentina. The study aims to study the long-term virological, immunological and clinical outcomes of PLHIV and to monitor temporal changes and regional differences in outcomes across Europe. Annually collected data include basic demographic characteristics, information on AIDS- and non-AIDS-related clinical events, and details about antiretroviral therapy (ART), hepatitis C treatment and other medications, in addition to a range of laboratory values. The summer 2016 data set held data from a total of 23 071 individuals contributing 174 481 person-years of follow-up, while EuroSIDA's unique plasma repository held over 160 000 samples. Over the past 25 years, close to 300 articles have been published in peer-reviewed journals (h-index 52), covering a range of scientific focus areas, including monitoring of clinical and virological outcomes, ART uptake, efficacy and adverse events, the influence of hepatitis virus coinfection, variation in the quality of HIV care and management across settings and regions, and biomarker research. Recognizing that there remain unresolved issues in the clinical care and management of PLHIV in Europe, EuroSIDA was one of the cohorts to found The International Cohort Consortium of Infectious Disease (RESPOND) cohort consortium on infectious diseases in 2017. In celebration of the EuroSIDA study's 25th anniversary, this article aims to summarize key scientific findings and outline current and future scientific focus areas.

Significance of Neoadjuvant Downstaging in Carcinoma of Esophagus and Gastroesophageal Junction.

OBJECTIVE: To determine the impact of downstaging on outcomes in esophageal cancer, the prognostic value of clinical and pathological stage, and the difference in survival in patients with similar pathological stages with and without neoadjuvant treatment. BACKGROUND: There is little data evaluating adenocarcinoma and squamous cell carcinoma (SCC) and difference in outcomes for similar pathological stage with and without neoadjuvant treatment. PATIENTS AND METHODS: Consecutive patients with esophageal cancer from a single center were evaluated. Patients with esophageal adenocarcinoma or SCC treated with transthoracic esophagectomy and two-field lymphadenectomy were included. Comparison of outcomes with those primarily treated with surgery was made. The cTNM and ypTNM 8th edition was used. RESULTS: This study included 992 patients, of whom 417 received surgery alone and 575 received neoadjuvant therapy and surgery. In the neoadjuvant group, 7 (1%) had cTNM stage 2 and 418 (73%) had cTNM stage 3. Downstaging rates were similar between adenocarcinoma and SCC (54% vs. 61%, p = 0.5). Downstaging was associated with longer survival than patients with no change (adenocarcinoma, median: 82 vs. 26 months, p < 0.001; SCC, median: NR vs. 29 months, p < 0.001). On Cox regression analysis, downstaging was associated with significantly longer survival in adenocarcinoma but not in SCC. For SCC and more advanced adenocarcinoma, overall survival was significantly better when comparing like-for-like ypTN to pTN groups. CONCLUSIONS: Pathological stage provides a better estimate of prognosis compared with clinical stage. Downstaged patients may have an improved outcome over those with comparable pathological stage who did not receive neoadjuvant treatment.

Anastomotic Leak Does Not Impact on Long-Term Outcomes in Esophageal Cancer Patients.

BACKGROUND: Esophagectomy is a technically demanding procedure associated with high levels of morbidity. Anastomotic leak (AL) is a common complication with potentially major ramifications for patients. It has also been associated with poorer long-term overall survival (OS) and disease recurrence. OBJECTIVE: The aim of this study was to determine whether AL contributes to poor OS and recurrence-free survival (RFS) for patients with esophageal cancer. METHODS: Consecutive patients undergoing a two-stage, two-field transthoracic esophagectomy from a single high-volume unit between 1997 and 2016 were evaluated. Clinicopathologic characteristics, along with oncological and postoperative outcomes, were stratified by no AL versus non-severe leak (NSL) versus severe esophageal AL (SEAL). SEAL was defined as ALs associated with Clavien-Dindo grade III/IV complications. RESULTS: This study included 1063 patients, of whom 8% (87/1063) developed AL; 45% of those who developed AL were SEALs (39/87). SEAL was associated with a prolonged critical care stay (median 8 vs. 3 vs. 2 days; p < 0.001) and prolonged hospital stay (median 43 vs. 27 vs. 15 days; p < 0.001) compared with NSL or no AL. There were no significant differences in number of lymph nodes harvested and rates of R1 resection between groups. OS and RFS were not affected by either NSL or SEAL, and Cox multivariate regression showed NSL and SEAL were not independently associated with OS and RFS. Sensitivity analysis in patients receiving neoadjuvant therapy followed by esophagectomy demonstrated similar findings. CONCLUSION: These results demonstrate that AL leads to prolonged critical care and in-hospital length of stay; however, contrary to previous reports, our results do not compromise long-term outcomes and are unlikely to have a detrimental oncological impact.

Impact of Lymphadenectomy on Survival After Unimodality Transthoracic Esophagectomy for Adenocarcinoma of Esophagus.

BACKGROUND: Debate remains regarding the extent of lymphadenectomy required with esophagectomy. In patients who receive neoadjuvant treatment, this may address lymph node metastases. However, patients with early disease and those with comorbidities may not receive neoadjuvant treatment. The aim of this study is to determine the impact of lymph node yield and location on prognosis in patients undergoing esophagectomy without neoadjuvant treatment. PATIENTS AND METHODS: Data from consecutive patients with potentially curable adenocarcinoma of the esophagus or gastroesophageal junction were reviewed. Patients were treated with transthoracic esophagectomy and two-field lymphadenectomy. Outcomes according to lymph node yield were determined. The prognosis of carrying out less radical lymphadenectomy was calculated according to three groups: exclusion of proximal thoracic nodes (group 1), minimal abdominal lymphadenectomy (group 2), and minimal abdominal and thoracic lymphadenectomy (group 3). RESULTS: 357 patients were included. Median survival was 78 months [confidence interval (CI) 53-103 months]. Absolute lymph node retrieval was not related to survival (p = 0.920). An estimated additional 4 (2-6) cancer-related deaths was projected if group 1 nodes were omitted, 15 (11-19) additional deaths if group 2 nodes were omitted, and 4 (2-6) deaths if group 3 nodes were omitted. Minimal lymphadenectomy (groups 1, 2, and 3) was projected to lead to 19 (15-23) additional cancer-related deaths. CONCLUSIONS: Extensive lymphadenectomy allows accurate staging. In patients who do not receive neoadjuvant treatment, it may confer a survival benefit. The number of lymph nodes retrieved may not be a good surrogate for extent of lymphadenectomy, and correlation with location is required.

Impact of anastomotic leak on long-term survival in patients undergoing gastrectomy for gastric cancer.

BACKGROUND: The impact of anastomotic leak (AL) on long-term outcomes after gastrectomy for gastric adenocarcinoma is poorly understood. This study determined whether AL contributes to poor overall survival. METHODS: Consecutive patients undergoing gastrectomy in a single high-volume unit between 1997 and 2016 were evaluated. Clinicopathological characteristics, oncological and postoperative outcomes were stratified according to whether patients had no AL, non-severe AL or severe AL. Severe AL was defined as anastomotic leakage associated with Clavien-Dindo Grade III-IV complications. RESULTS: The study included 969 patients, of whom 58 (6·0 per cent) developed AL; 15 of the 58 patients developed severe leakage. Severe AL was associated with prolonged hospital stay (median 50, 30 and 13 days for patients with severe AL, non-severe AL and no AL respectively; P < 0·001) and critical care stay (median 11, 0 and 0 days; P < 0·001). There were no significant differences between groups in number of lymph nodes harvested (median 29, 30 and 28; P = 0·528) and R1 resection rates (7, 5 and 6·5 per cent; P = 0·891). Cox multivariable regression analysis showed that severe AL was independently associated with overall survival (hazard ratio 3·96, 95 per cent c.i. 2·11 to 7·44; P < 0·001) but not recurrence-free survival. In sensitivity analysis, the results for patients who had neoadjuvant therapy then gastrectomy were similar to those for the entire cohort. CONCLUSION: AL prolongs hospital stay and is associated with compromised long-term overall survival.

ANTECEDENTES: El impacto de la fuga anastomótica (anastomotic leak, AL) tras una gastrectomía por adenocarcinoma gástrico sobre los resultados a largo plazo es poco conocido. En este estudio se investigó si la AL contribuye a una peor supervivencia global (overall survival, OS). MÉTODOS: Se analizaron todos los pacientes consecutivos sometidos a una gastrectomía en un centro de alto volumen entre 1997 y 2016. Las características clinicopatológicas, los resultados postoperatorios y los resultados oncológicos se clasificaron en función de la AL: no AL versus NSL (Non-Severe Leak, fuga no grave) versus AL grave (severe AL, SAL). SAL se definió como fugas anastomóticas asociadas con complicaciones Clavien-Dindo grado III / IV. RESULTADOS: Se incluyeron 969 pacientes en el estudio, de los cuales el 6% (58/969) presentó una AL. De los que desarrollaron AL, el 26% desarrolló SAL (15/58). SAL se asoció con una estancia prolongada en el hospital (mediana: 50 versus 30 versus 13 días, P < 0,001) y en cuidados intensivos (mediana: 11 versus 0 versus 0 días, P < 0,001) en comparación con NSL o sin AL. No hubo diferencias significativas en los ganglios linfáticos identificados (mediana: 28 versus 30 versus 29 P = 0,5) ni en las tasas de resección R1 (mediana: 7% versus 5% versus 7%, P = 0,9) entre no AL, NSL y SAL, respectivamente. La regresión multivariable de Cox demostraba que SAL se asociaba independientemente con la OS (cociente de riesgos instantáneos, hazard ratio, HR 3,96, i.c. del 95% 2,11-7,44, P < 0,001) pero no la RFS. El análisis de sensibilidad en pacientes que recibieron tratamiento neoadyuvante y posteriormente gastrectomía fue similar a los que se sometieron únicamente a gastrectomía. CONCLUSIÓN: La AL prolonga la estancia hospitalaria y compromete la supervivencia global a largo plazo.

Investigating Conceptual Models for the Relationship Between Depression and Condomless Sex Among Gay, Bisexual, and Other Men Who have Sex with Men: Using Structural Equation Modelling to Assess Mediation.

The aim of this study is to investigate five hypothesized mechanisms of causation between depression and condomless sex with ≥ 2 partners (CLS2+) among gay, bisexual, and other men who have sex with men (GBMSM), involving alternative roles of self-efficacy for sexual safety and recreational drug use. Data were from the AURAH cross-sectional study of 1340 GBMSM attending genitourinary medicine clinics in England (2013-2014). Structural equation modelling (SEM) was used to investigate which conceptual model was more consistent with the data. Twelve percent of men reported depression (PHQ-9 ≥ 10) and 32% reported CLS2+ in the past 3 months. AURAH data were more consistent with the model in which depression was considered to lead to CLS2+ indirectly via low self-efficacy for sexual safety (indirect Beta = 0.158; p < 0.001) as well as indirectly via higher levels of recreational drug use (indirect Beta = 0.158; p < 0.001). SEM assists in understanding the relationship between depression and CLS among GBMSM.