Princess Royal University Hospital

This position document has been developed by the Dysphagia Working Group, a committee of members from the European Society for Swallowing Disorders and the European Union Geriatric Medicine Society, and invited experts. It consists of 12 sections that cover all aspects of clinical management of oropharyngeal dysphagia (OD) related to geriatric medicine and discusses prevalence, quality of life, and legal and ethical issues, as well as health economics and social burden. OD constitutes impaired or uncomfortable transit of food or liquids from the oral cavity to the esophagus, and it is included in the World Health Organization's classification of diseases. It can cause severe complications such as malnutrition, dehydration, respiratory infections, aspiration pneumonia, and increased readmissions, institutionalization, and morbimortality. OD is a prevalent and serious problem among all phenotypes of older patients as oropharyngeal swallow response is impaired in older people and can cause aspiration. Despite its prevalence and severity, OD is still underdiagnosed and untreated in many medical centers. There are several validated clinical and instrumental methods (videofluoroscopy and fiberoptic endoscopic evaluation of swallowing) to diagnose OD, and treatment is mainly based on compensatory measures, although new treatments to stimulate the oropharyngeal swallow response are under research. OD matches the definition of a geriatric syndrome as it is highly prevalent among older people, is caused by multiple factors, is associated with several comorbidities and poor prognosis, and needs a multidimensional approach to be treated. OD should be given more importance and attention and thus be included in all standard screening protocols, treated, and regularly monitored to prevent its main complications. More research is needed to develop and standardize new treatments and management protocols for older patients with OD, which is a challenging mission for our societies.

BACKGROUND: Patent foramen ovale (PFO) is prevalent in patients with migraine with aura. Observational studies show that PFO closure resulted in migraine cessation or improvement in approximately 80% of such patients. We investigated the effects of PFO closure for migraine in a randomized, double-blind, sham-controlled trial. METHODS AND RESULTS: Patients who suffered from migraine with aura, experienced frequent migraine attacks, had previously failed > or = 2 classes of prophylactic treatments, and had moderate or large right-to-left shunts consistent with the presence of a PFO were randomized to transcatheter PFO closure with the STARFlex implant or to a sham procedure. Patients were followed up for 6 months. The primary efficacy end point was cessation of migraine headache 91 to 180 days after the procedure. In total, 163 of 432 patients (38%) had right-to-left shunts consistent with a moderate or large PFO. One hundred forty-seven patients were randomized. No significant difference was observed in the primary end point of migraine headache cessation between implant and sham groups (3 of 74 versus 3 of 73, respectively; P=0.51). Secondary end points also were not achieved. On exploratory analysis, excluding 2 outliers, the implant group demonstrated a greater reduction in total migraine headache days (P=0.027). As expected, the implant arm experienced more procedural serious adverse events. All events were transient. CONCLUSIONS: This trial confirmed the high prevalence of right-to-left shunts in patients with migraine with aura. Although no significant effect was found for primary or secondary end points, the exploratory analysis supports further investigation. The robust design of this study has served as the model for larger trials that are currently underway in the United States and Europe.

Post-stroke dysphagia (a difficulty in swallowing after a stroke) is a common and expensive complication of acute stroke and is associated with increased mortality, morbidity, and institutionalization due in part to aspiration, pneumonia, and malnutrition. Although most patients recover swallowing spontaneously, a significant minority still have dysphagia at six months. Although multiple advances have been made in the hyperacute treatment of stroke and secondary prevention, the management of dysphagia post-stroke remains a neglected area of research, and its optimal management, including diagnosis, investigation and treatment, have still to be defined.

AIMS: To examine the changes in coronary, all-cause, and cancer mortality in patients with heterozygous familial hypercholesterolaemia (FH) before and after lipid-lowering therapy with statins. METHODS AND RESULTS: A total of 3382 patients (1650 men) aged <80 years were recruited from 21 lipid clinics in the United Kingdom and followed prospectively between 1980 and 2006 for 46 580 person-years. There were 370 deaths, including 190 from coronary heart disease (CHD) and 90 from cancer. The standardized mortality ratio (compared with the population in England and Wales) was calculated before and from 1 January 1992. In patients aged 20-79 years, CHD mortality fell significantly by 37% (95% CI = 7-56) from 3.4- to 2.1-fold excess. Primary prevention resulted in a 48% reduction in CHD mortality from 2.0-fold excess to none, with a smaller reduction of nearly 25% in patients with established disease. Coronary mortality was reduced more in women than in men. In patients without known CHD at registration, all-cause mortality from 1992 was 33% (21-43), lower than in the general population, mainly due to a 37% (21-50) lower risk of fatal cancer. CONCLUSION: The results emphasize the importance of early identification of FH and treatment with statins.

Reinke's space is a critical laryngeal structure, and the eponym remains in current use in both clinical and research settings. However, little is known about the life of the German anatomist Friedrich Berthold Reinke. His name is missing from the otolaryngological histories, despite his work on the structure he described being responsible for a fundamental advance in our understanding of the larynx. Although brilliant, Reinke was described as impetuous and coarse by his colleagues, resulting in his academic career being cut short. Reinke's relative anonymity is thought to derive from the fact that he never defined himself as a laryngologist. Without question, Reinke's observations of the human vocal fold are substantive contributions, without which modern laryngology could not have evolved. This article aimed to summarise this brilliant yet troubled man's life and achievements, allowing appreciation for his singular genius and fundamental contribution to laryngology.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist.

Pain is a key unmet need and a major aspect of non-motor symptoms of Parkinson's disease (PD). No specific validated scales exist to identify and grade the various types of pain in PD. We report an international, cross-sectional, open, multicenter, one-point-in-time evaluation with retest study of the first PD-specific pain scale, the King's PD Pain Scale. Its seven domains include 14 items, each item scored by severity (0-3) multiplied by frequency (0-4), resulting in a subscore of 0 to 12, with a total possible score range from 0 to 168. One hundred seventy-eight PD patients with otherwise unexplained pain (age [mean ± SD], 64.38 ± 11.38 y [range, 29-85]; 62.92% male; duration of disease, 5.40 ± 4.93 y) and 83 nonspousal non-PD controls, matched by age (64.25 ± 11.10 y) and sex (61.45% males) were studied. No missing data were noted, and floor effect was observed in all domains. The difference between mean and median King's PD Pain Scale total score was less than 10% of the maximum observed value. Skewness was marginally high (1.48 for patients). Factor analysis showed four factors in the King's PD Pain Scale, explaining 57% of the variance (Kaiser-Mayer-Olkin, 0.73; sphericity test). Cronbach's alpha was 0.78, item-total correlation mean value 0.40, and item homogeneity 0.22. Correlation coefficients of the King's PD Pain Scale domains and total score with other pain measures were high. Correlation with the Scale for Outcomes in PD-Motor, Non-Motor Symptoms Scale total score, and quality of life measures was high. The King's PD Pain Scale seems to be a reliable and valid scale for grade rating of various types of pain in PD.

Bupropion has been used as an antidepressant for over 20 years, though its licence for such use varies and it is typically a third- or fourth-line agent. It has a unique pharmacology, inhibiting the reuptake of noradrenaline and dopamine, potentially providing pharmacological augmentation to more common antidepressants such as selective serotonergic reuptake inhibitors (SSRIs). This systematic review and meta-analysis identified 51 studies, dividing into four categories: bupropion as a sole antidepressant, bupropion coprescribed with another antidepressant, bupropion in 'other' populations (e.g. bipolar depression, elderly populations) and primary evaluation of side effects. Methodologically more robust trials support the superiority of bupropion over placebo, and most head-to-head antidepressant trials showed an equivalent effectiveness, though some of these are hindered by a lack of a placebo arm. Most work on the coprescribing of bupropion with another antidepressant supports an additional effect, though many are open-label trials. Several large multi-medication trials, most notably STAR*D, also support a therapeutic role for bupropion; in general, it demonstrated similar effectiveness to other medications, though this literature highlights the generally low response rates in refractory cohorts. Effectiveness has been shown in 'other' populations, though there is an overall dearth of research. Bupropion is generally well tolerated, it has very low rates of sexual dysfunction, and is more likely to cause weight loss than gain. Our findings support the use of bupropion as a sole or coprescribed antidepressant, particularly if weight gain or sexual dysfunction are, or are likely to be, significant problems. However there are notable gaps in the literature, including less information on treatment naïve and first presentation depression, particularly when one considers the ever-reducing rates of response in more refractory illness. There are some data to support bupropion targeting specific symptoms, but insufficient information to reliably inform such prescribing, and it remains uncertain whether bupropion pharmacodynamically truly augments other drugs.

Urinary tract infections (UTIs) are the most common bacterial infection in pregnancy, increasing the risk of maternal and neonatal morbidity and mortality. Urinary tract infections may present as asymptomatic bacteriuria, acute cystitis or pyelonephritis. Escherichia coli is the most common pathogen associated with both symptomatic and asymptomatic bacteriuria. If asymptomatic bacteriuria is untreated, up to 30% of mothers develop acute pyelonephritis, with an increased risk of multiple maternal and neonatal complications, such as preeclampsia, preterm birth, intrauterine growth restriction and low birth weight. Urinary tract infection is a common, but preventable cause of pregnancy complications, thus urinary tests, such as urine culture or new technologies such as high-throughput DNA sequence-based analyses, should be used in order to improve antenatal screening of pregnant women.

There has been growing clinical, public, and media awareness and concern about the availability and potential harmfulness of so-called 'legal highs', which are more appropriately called new or novel psychoactive substances (NPS). A cat-and-mouse process has emerged wherein unknown chemists and laboratories are producing new, and as yet nonproscribed, compounds for human consumption; and as soon as they are banned, which they inevitably are, slightly modified analogues are produced to circumvent new laws. This rapidly changing environment, 81 new substances were identified in 2013 alone, has led to confusion for clinicians, psychopharmacologists, and the public at large. Our difficulties in keeping up with the process has had a two-fold negative effect: the danger of ignoring what is confusing; and the problem that some of the newer synthesized compounds appear ever more potent. This review aims to circumscribe a quick moving and growing field, and to categorize NPS into five major groups based upon their 'parent' compounds: stimulants similar to cocaine, amphetamines and ecstasy; cannabinoids; benzodiazepine based drugs; dissociatives similar to ketamine and phencyclidine (PCP); and those modelled after classic hallucinogens such as LSD and psilocybin. Pharmacodynamic actions, subjective and physical effects, harmfulness, risk of dependency and, where appropriate, putative clinical potentials are described for each class. Clinicians might encounter NPS in various ways: anecdotal reportage; acute intoxication; as part of a substance misuse profile; and as a precipitant or perpetuating factor for longer-term physical and psychological ill health. Current data are overall limited, and much of our knowledge and treatment strategies are based upon those of the 'parent' compound. There is a critical need for more research in this field, and for professionals to make themselves more aware of this growing issue and how it might affect those we see clinically and try to help: a brave new world of so-called 'psychonauts' consuming NPS will also need informed 'psychotherapeutonauts'. The paper should serve as a primer for clinicians and interested readers, as well as provide a framework into which to place the new substances that will inevitably be synthesized in the future.

Owing to their ability to efficiently deliver biological cargo and sense the intracellular milieu, vertical arrays of high aspect ratio nanostructures, known as nanoneedles, are being developed as minimally invasive tools for cell manipulation. However, little is known of the mechanisms of cargo transfer across the cell membrane-nanoneedle interface. In particular, the contributions of membrane piercing, modulation of membrane permeability and endocytosis to cargo transfer remain largely unexplored. Here, combining state-of-the-art electron and scanning ion conductance microscopy with molecular biology techniques, it is shown that porous silicon nanoneedle arrays concurrently stimulate independent endocytic pathways which contribute to enhanced biomolecule delivery into human mesenchymal stem cells. Electron microscopy of the cell membrane at nanoneedle sites shows an intact lipid bilayer, accompanied by an accumulation of clathrin-coated pits and caveolae. Nanoneedles enhance the internalization of biomolecular markers of endocytosis, highlighting the concurrent activation of caveolae- and clathrin-mediated endocytosis, alongside macropinocytosis. These events contribute to the nanoneedle-mediated delivery (nanoinjection) of nucleic acids into human stem cells, which distribute across the cytosol and the endolysosomal system. This data extends the understanding of how nanoneedles modulate biological processes to mediate interaction with the intracellular space, providing indications for the rational design of improved cell-manipulation technologies.

The burden of depressive disorders and the frequent inadequacy of their current pharmacological treatments are well established. The anaesthetic and hallucinogenic drug ketamine has provoked much interest over the past decade or so as an extremely rapidly acting antidepressant that does not modify 'classical' monoaminergic receptors. Current evidence has shown several ways through which it might exert therapeutic antidepressant actions: blockade of glutamatergic NMDA receptors and relative upregulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) subtypes may alter cortical connectivity patterns; through intracellular changes in protein expression, including the proteins mammalian target of rapamycin (mTOR) and brain-derived neurotrophic factor (BDNF); and alteration of intracellular signalling cascades. The clinical evidence demonstrates rapid improvements in mood and suicidal thinking in most participants, although study numbers have generally been small and many trials are unblinded and methodologically weak. There is a small body of work to suggest ketamine might also augment electroconvulsive therapy and potentially have a role as a surgical anaesthetic in depressed patients. A major problem is that the effects of ketamine appear temporary, disappearing after days to weeks (although longer benefits have been sustained in some), and attempts to circumvent this through pharmacological augmentation have been disappointing thus far. These exciting data are providing new insights into neurobiological models of depression, and potentially opening up a new class of antidepressants, but there are significant practical and ethical issues about any future mainstream clinical role it might have.

UNLABELLED: Laparoscopic cholecystectomy is the treatment of choice for gall bladder stone disease. Difficult cholecystectomy is associated with serious complications and a high conversion rate. The aim of this study was to review the current strategies to manage difficult cholecystectomy. METHODS: A Medline search was conducted to review all published English literatures relevant to difficult cholecystectomy through 1993 to 2009. The search words were "laparoscopic cholecystectomy," "difficult cholecystectomy," "difficult laparoscopy," "subtotal laparoscopic cholecystectomy," "fundus first cholecystectomy," and "causes of conversion of laparoscopic cholecystectomy." RESULTS: Ninety-one studies, which included 324,553 patients, were selected for this review. Five major categories of difficulty were identified. Conversion rate and iatrogenic injuries during laparoscopic cholecystectomy are still high despite significant improvement over the last 10 years. Depending on the technique of cholecystectomy, the degree of gall bladder inflammation, patient comorbidities, and surgical experience, the conversion rate was reported between 0.18% and 30%, whereas the incidence of iatrogenic injuries was from 0% to 0.6%. Subtotal cholecystectomy, antegrade and fundus first techniques, and peroperative cholangiogram were associated with lower complications and conversion rate. Risk factors for difficulty were male sex, increased age, acute and thick wall chronic cholecystitis, wide and short cystic duct, cholecystodigestive fistula, previous upper abdominal surgery, obesity, liver cirrhosis, anatomic variation, cholangiocarcinoma, and low surgeon's caseload. CONCLUSIONS: No consensus is found among surgeons on how to manage difficult laparoscopic cholecystectomy. Iatrogenic injuries and conversion rate can be reduced depending on the surgeon's experience, special techniques, and intraoperative investigations. Subtotal cholecystectomy, antegrade or fundus first techniques, and peroperative cholangiogram significantly reduced the complications and conversion rate.

AIMS: This study describes the use of the Masquelet technique to treat segmental tibial bone loss in 12 patients. PATIENTS AND METHODS: This retrospective case series reviewed 12 patients treated between 2010 and 2015 to determine their clinical outcome. Patients were mostly male with a mean age of 36 years (16 to 62). The outcomes recorded included union, infection and amputation. The mean follow-up was 675 days (403 to 952). RESULTS: The mean tibial defect measured 5.8 cm (2 to 15) in length. Of the 12 patients, 11 had an open fracture. Eight underwent fixation with an intramedullary nail, three with plates and one with a Taylor Spatial Frame. The mean interval between stages was 57 days (35 to 89). Bony union was achieved in only five patients. Five patients experienced infective complications during treatment, with two requiring amputation because of severe infection. CONCLUSION: 2017;99-B:680-5.

Hallucinogens have been part of spiritual practice for millennia, but controversy surrounding their mind-manifesting effects led to their proscription by the mid-20th century, largely without evidence of harm or toxicity and despite nascent data suggesting therapeutic utility in treating depressive illnesses. This review explores their pharmacodynamic actions and the current limited data on their clinic effectiveness. These drugs appear to exert their psychedelic effects through their agonist or partial agonist activity at the serotonergic 5-HT2A receptor, though they also have affinity for other metabotropic serotonin receptors. Hallucinogen binding affects a wide range of intracellular signalling pathways, the precise nature of which remains incompletely understood. They alter the serotonergic tone of brainstem raphe nuclei that project through the brain; they interact with receptors in the prefrontal cortex altering connectivity patterns and intracellular functioning; and they disrupt inhibitory control of sensory input via the thalamus to the cortex. The serotonergic system has long been implicated in anxiety and depressive disorders, and is a major target of most existing antidepressants. Classical hallucinogens alter the functioning of this system, but not in the same way current medications do: whilst there are identified receptors and neurotransmitter pathways through which hallucinogens could therein produce therapeutic effects, the neurobiology of this remains speculative at this time. There is currently an extremely limited but growing literature on hallucinogen safety and clinical application. The drugs appear well tolerated by healthy controls and clinical populations, and the rapid tolerance to repeated administration might reduce the possibility of dependency. Clinical trials reported over the past decade have generally shown positive therapeutic potential, but they are notably few in number. Legislative policy has had a freezing effect on evaluation of these compounds, a better understanding of which might improve our knowledge of the processes involved in consciousness, the neuropathology of depression, and potentially open up new pharmacological therapies.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), emerged at the end of 2019 and caused an infection named coronavirus disease 19 (COVID-19).1 Patients with compromised immune systems are at increased risk of complications of COVID-19 but this risk is not precisely defined.2 Although age, gender, comorbidities and ethnicity are risk factors for adverse outcomes,3 various pre-existing conditions, including haematological cancers, have also been reported to correlate with poor outcomes.4-8 Our aim was to compare the first 80 patients with a haematological malignancy with all other patients admitted to our hospital with COVID-19 in the same time frame, to precisely define their relative risk and identify factors that increase mortality within this subgroup. The mean age of our cohort was 69·4 years (range 30–95 years); 52 (65%) males; 76% had at least one comorbidity. Overall, 62 (77%) patients had lymphoid malignancies/plasma cell dyscrasias and 18 (23%) had myeloid neoplasms. Nine patients had previously undergone allogeneic (n = 6) and autologous (n = 3) haematopoietic stem cell transplantation. One patient had received chimeric antigen receptor T-cell (CAR-T) therapy. Treatment type included intensive therapy (n = 16; 20%,), non-intensive therapy (n = 35; 44%) and ‘watch and wait’ (n = 29, 36%), with 31 (40%) on active treatment (Tables SI and SII). The most common symptoms on admission were fever (60%), cough (58%), dyspnoea (54%) and gastrointestinal symptoms (13%) (Table SI). Both the baseline pre-COVID-19 (median 1·25 × 109/l) and the nadir (median 0·6 × 109/l) lymphocyte count were lower than the normal range (1·3–4). Overall, 23 (29%) patients had a mild symptoms, 22 (27%) had moderate symptoms needing ward-based care and oxygen and 35 (44%) had severe symptoms. On the date of censoring, 28 patients had died due to COVID-19, with a crude case fatality rate of 39%. The haemato-oncology patients who died or were transferred to the intensive care unit were older (73 vs. 66 years; P = 0·065); but male gender (61% vs. 67%, P = 0·76) was not associated with poorer outcome. Differences in ethnicity were noted, with a higher black population among those who died (45% vs. 17%, P = 0·02). Higher total white cell count (15·8 vs. 4·9 × 109/l, P = 0·015), neutrophil count (5·7 vs. 3·8 × 109/l, P = 0·04) and C-reactive protein (CRP) (200 vs. 82, P < 0·001) were associated with poorer outcome (Table SI). A lower baseline pre-COVID-19 lymphocyte count (1·1 vs. 1·5 × 109/l, P = 0·02) was associated with better outcome, even when chronic lymphocytic leukaemia (CLL) cases were removed from the analysis. Figure S1 shows the fall in lymphocyte count from before COVID-19 infection to its nadir during COVID-19 infection. We compared baseline characteristics and outcome of COVID-19 in hospitalised patients with no underlying haematological malignancy (n = 1115) with our haemato-oncology cohort (n = 68) (Table I), admitted within the same time frame where identical follow-up was available. No difference was observed in age, gender or comorbidities between the two groups. There was a higher proportion (60·3% vs. 45%, P = 0·011) of white British and lower incidence of social deprivation (22% vs. 40·3%, P = 0·018) in the haemato-oncology cohort. The median lymphocyte and neutrophil count were lower (0·6 vs. 1·0 × 109/l, P < 0·001 and 3·8 vs. 5·7 × 109/l, P < 0·001 respectively) in the haemato-oncology group. The crude mortality rate at day 28 from admission was significantly worse for the haemato- oncology cohort 39% (95% CI: 27–52) versus 20% (95% CI: 18–23) in the medical cohort (hazard ratio (HR) 2·06; 95% CI: 1·36–3·14; P = 0·001] and was retained on adjusting for age and gender (HR 1·74; 95% CI: 1·12–2·71; P = 0·014) (Table SIII and Fig 1A,B). Although the type of underlying malignancy (lymphoid vs. myeloid), did not influence the outcome (Table SIII and Fig 1C), the intensity of treatment had a strongly negative impact on mortality. Patients on both intensive (HR 4·66; 95% CI: 2·29–9·47; P = 0·001) and non-intensive (HR 1·90; 95% CI: 1·05–3·48; P = 0·035) treatments, did worse compared with the age- and gender-matched general cohort (Table SIII and Figure S2D). SARS-CoV-2 ribonucleic acid (RNA) was detected in nasopharyngeal swabs/bronchoalveolar lavage in all 80 patients. We evaluated the persistence of viral RNA in 22 patients who had a repeat positive test beyond 7 days. The median duration of virus detection in the respiratory samples was 29 days (Figure S2A). Of the 22 patients, nine became negative at a median of 13 days (range 7–60) and 13 patients had ongoing RNA persistence (Figures S2 and S3). We noted several cases of clinical deterioration beyond the 10–14 day window. In conclusion, we report on outcomes and predictive factors for the largest series to date of patients with COVID-19 and underlying haematological malignancies (n = 80) and compare outcomes to general medical patients admitted with COVID-19 during the same time. We found no correlation between age or male gender between survivors and non-survivors with COVID-19 and haematological cancer, compared to a general, non-haematology cohort, and contrary to previous publications.1 However, haemato-oncology patients with COVID-19 had a twofold increased risk of death, with a 28-day mortality rate of 39%, which was fourfold higher in those undergoing intensive treatment. Our data suggests that the current caution around delivery of intensive treatments during the COVID-19 outbreak is justified and that continuation of shielding in this subgroup should be considered. Lymphopenia during COVID-19 is present in high proportion (40–83%) of cases and is also associated with a worse prognosis in the general population.1, 3, 9, 10 Our data show a lower lymphocyte and neutrophil count in the haematology cohort. Furthermore, both worsening of lymphopenia during and the depth of lymphopenia prior to infection had a beneficial impact on survival. This is in line with several recent studies suggesting that overactivation of the adaptive immune system can be responsible for the high mortality associated with COVID-19. This is, however, speculative and further study of both innate and adaptive immunity within the haematology cohort may be useful. Prolonged detection of viral RNA, for up to 2 months in a subset of patients, has not been reported in the immunocompromised setting.11 Prolonged persistence in haemato-oncology patients has significant implications for scheduling subsequent chemotherapy, shielding and self-isolation. Despite limitations and caveats, our data, with the added benefit of a large cohort of non-haematology COVID-19 patients, show a doubling of mortality in haemato-oncology patients with COVID-19 and a prolonged persistence of viral RNA. The authors wish to thank the patients and all the staff who were involved in managing COVID-19 at our institution. The authors declare no conflicts of interest. VS, TKK, MZ and AGK designed the concept, collected and analysed data, and wrote the manuscript. SN and JG collected data for the medical cohort and did statistical analysis. JV, SS, VM, SG, AK, DY, DA, RS, CR, AS, JM, HDL, PK, RB, PP, VP, MMC, GJM, AP and AGK enrolled patients and provided clinical data. All authors reviewed and approved the final version. Fig S1. Paired boxplot of lymphocyte count × 109 of patients with haematological malignancy prior to COVID-19 and their nadir lymphocyte count in cohort of patients without CLL (a) and CLL patients (b). Fig S2. 1A Duration of swab positivity in two groups – remained positive at last testing (red) and negative swab at the last testing (green). Fig S3. Dynamics of viral load, as assessed by semi-quantitative RT-PCR, represented as change from baseline and duration of swab positivity. Table SI. Treatment intensity groups (intensive vs. non-intensive vs. surveillance). Table SII. Baseline demographics and COVID-19-related features (n = 80) and comparison of patients with known outcomes who died or went to ITU compared to those who recovered (n = 75). Table SIII. Hazards Table (compared to non-haematology COVID-19 cohort, group 2). 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This review aims to provide an update on the role of augmented reality (AR) in surgical training and investigate whether the use of AR improves performance measures compared to traditional approaches in surgical trainees. PUBMED, EMBASE, Google Scholar, Cochrane Library, British Library and Science Direct were searched following PRIMSA guidelines. All English language original studies pertaining to AR in surgical training were eligible for inclusion. Qualitative analysis was performed and results were categorised according to simulator models, subsequently being evaluated using Messick's framework for validity and McGaghie's translational outcomes for simulation-based learning. Of the 1132 results retrieved, 45 were included in the study. 29 platforms were identified, with the highest 'level of effectiveness' recorded as 3. In terms of validity parameters, 10 AR models received a strong 'content validity' score of 2.15 models had a 'response processes' score ≥ 1. 'Internal structure' and 'consequences' were largely not discussed. 'Relations to other variables' was the best assessed criterion, with 9 platforms achieving a high score of 2. Overall, the Microsoft HoloLens received the highest level of recommendation for both validity and level of effectiveness. Augmented reality in surgical education is feasible and effective as an adjunct to traditional training. The Microsoft HoloLens has shown the most promising results across all parameters and produced improved performance measures in surgical trainees. In terms of the other simulator models, further research is required with stronger study designs, in order to validate the use of AR in surgical training.

AIMS: Admission rates for acute decompensated heart failure (HF) declined during the COVID-19 pandemic. However, the impact of this reduction on hospital mortality is unknown. We describe temporal trends in the presentation of patients with acute HF and their in-hospital outcomes at two referral centres in London during the COVID-19 pandemic. METHODS AND RESULTS: A total of 1372 patients hospitalized for HF in two referral centres in South London between 7 January and 14 June 2020 were included in the study and their outcomes compared with those of equivalent patients of the same time period in 2019. The primary outcome was all-cause in-hospital mortality. The number of HF hospitalizations was significantly reduced during the COVID-19 pandemic, compared with 2019 (P < 0.001). Specifically, we observed a temporary reduction in hospitalizations during the COVID-19 peak, followed by a return to 2019 levels. Patients admitted during the COVID-19 pandemic had demographic characteristics similar to those admitted during the equivalent period in 2019. However, in-hospital mortality was significantly higher in 2020 than in 2019 (P = 0.015). Hospitalization in 2020 was independently associated with worse in-hospital mortality (hazard ratio 2.23, 95% confidence interval 1.34-3.72; P = 0.002). CONCLUSIONS: During the COVID-19 pandemic there was a reduction in HF hospitalization and a higher rate of in-hospital mortality. Hospitalization for HF in 2020 is independently associated with more adverse outcomes. Further studies are required to investigate the predictors of these adverse outcomes to help inform potential changes to the management of HF patients while some constraints to usual care remain.

BACKGROUND: Laparoscopic surgery is widely practiced and offers realistic benefits over conventional surgery. There is considerable variation in results between surgeons, concerning port-site complications. The aim of this study was to evaluate the laparoscopic port closure technique and to explore the factors associated with port-site incisional hernia. METHODS: Between January 2000 and January 2007, 5541 laparoscopic operations were performed by a single consultant surgeon for different indications. The ports were closed by the classical method using a J-shaped needle after release of pneumoperitoneum. The incidence of port-site incisional hernias was calculated. All patients were followed up by outpatient clinic visits and by their general practitioners. RESULTS: During a 6-year period, 5541 laparoscopic operations were performed. Eight patients (0.14%) developed port-site hernia during a mean follow-up period of 43 months (range, 25 to 96) and required elective surgery to repair their hernias. No major complications or mortality was reported. CONCLUSION: Laparoscopic port closure using the classical method was associated with an acceptable incidence of port-site hernia. Modification of the current methods of closure may lead to a new technique to prevent or reduce the incidence of port-site incisional hernias.

BACKGROUND: Patients with inflammatory bowel disease (IBD) have identified a need for more information about their disease. PURPOSE: To assess the effect of an educational intervention on health-related quality of life (HRQOL) in patients with IBD. METHODS: Consecutive ambulatory IBD patients were randomized to receive four IBD-specific educational booklets or usual care. Subjects completed two disease-specific HRQOL questionnaires-the Inflammatory Bowel Disease Questionnaire (IBDQ) (range 1-poor to 7-excellent) and the Quality Index in Crohn's and Colitis (QuICC) (range 1-excellent to 5-poor) at entry and after 2 weeks. The mean change in HRQOL scores at follow-up was compared between the education and control groups. RESULTS: 59 subjects participated, with a mean age of 40.0 +/- 11.9 years. 34 were given educational booklets and 25 received standard care. 6 patients (10%) did not complete the study. Mean IBDQ scores became significantly worse in the education group with a change of -0.17 +/- 0.49 compared with controls at +0.28 +/- 0.62 (p = 0.006). This could be explained by worsened disease activity in the education group. There was no significant change in the QuICC scores (p = 0.61). Education group patients who had not received prior educational material had improved mean IBDQ scores of +0.24 +/- 0.47 compared with education patients who had received educational material prior to this study, with a score change of -0.25 +/- 0.46 (p = 0.09). CONCLUSIONS: The addition of educational booklets to IBD patients in a tertiary center does not improve, and may worsen, short-term HRQOL. Education of newly diagnosed or less informed patients should be studied further.