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Background Antiretroviral therapy (ART)-related weight gain is of particular concern in people with HIV (PWH). Although weight gain was observed among PWH receiving tenofovir alafenamide (TAF), little is known about the potential reversibility after TAF discontinuation. We evaluated weight and metabolic changes 12 months after TAF discontinuation in the Swiss HIV Cohort Study. Methods We included participants who received at least 6 months of TAF-containing ART between January 2016 and March 2023. Using multivariable mixed-effect models, changes in weight and lipid levels were compared between individuals who continued TAF and those who switched to one of the following TAF-free regimens: (1) tenofovir disoproxil fumarate (TDF)-based ART, (2) dolutegravir/lamivudine (DTG/3TC), or (3) long-acting cabotegravir/rilpivirine (CAB/RPV). Results Of 6555 participants (median age 54 years, 24.3% female, 13% Black), 5485 (83.7%) continued, and 1070 (16.3%) stopped TAF. Overall, discontinuing TAF was associated with an adjusted mean weight change of −0.54 kg (95% confidence interval [CI] −.98 to −.11) after 12 months. In stratified analyses, switching from TAF to TDF led to an adjusted mean weight decrease of −1.84 kg (95% CI −2.72 to −.97), and to a decrease in mean total cholesterol (−0.44 mmol/L) and triglycerides (−0.38 mmol/L) after 12 months. Switching from TAF-based ART to DTG/3TC (−0.17 kg, 95% CI −.82 to.48) or long-acting CAB/RPV (−0.64 kg, 95% CI −2.16 to.89) did not lead to reductions in weight. Conclusions Replacing TAF with TDF in PWH led to a decrease in body weight and an improved lipid profile within 1 year. Weight changes were not observed among individuals who switched to DTG/3TC or long-acting CAB/RPV. [ABSTRACT FROM AUTHOR]

Necrotizing soft tissue infections (NSTIs) are associated with significant mortality if not promptly diagnosed and surgically treated. This study aims to compare patients with severe skin and soft tissue infection treated with or without a surgical intervention and to identify risk factors that can predict the need for early surgery. Demographics, clinical, laboratory, Risk Indicator for Necrotizing Fasciitis (LRINEC) and imaging results were retrospectively collected. There were 91 non-NSTI (group 1), 26 NSTI who were operated (group 2) and eight suspected NSTI who were not operated (group 3). In the multivariate analysis, skin necrosis, tachycardia, CRP value and hyperglycemia were predictive for surgery. A performance analysis revealed AUC of 0.65 (95%CI: 0.52–0.78) as to the LRINEC score for the use of surgery. The AUC for a predictive model associating four variables (heart rate, skin necrosis, CRP and glycemia at admission) was 0.71 (95%CI: 0.59–0.84). In terms of outcome, the median length of stay (LOS) was statistically higher in group 2 vs. group 1 (seven days (5–15) vs. 34 days (20–42), p <.001) and in group 2 vs. group 3 (34 days (20–42) vs. 14 days (11–19), p =.005). The overall in-hospital mortality at 30 days was 3.2% and did not statistically differ between the three groups. Although the LRINEC score performed well in predicting surgery, the AUC of a model combining four predictive variables (glycemia, skin necrosis, CRP and heart rate) was superior. Further research is needed to validate this model. [ABSTRACT FROM AUTHOR]

Long‐acting cabotegravir has been studied mainly in the stringent framework of clinical trials, which does not necessarily reflect the situation of people with HIV (PWH) in routine clinical settings. The present population pharmacokinetic analysis aims to build real‐world reference percentile curves of cabotegravir concentrations, accounting for patient‐related factors that may affect cabotegravir exposure. The second objective is to simulate whether dosing interval adjustments of cabotegravir could be considered in specific subpopulations. Overall, 238 PWH contributed to 1,038 cabotegravir levels (186 during the initial oral administration phase and 852 after intramuscular injection). Cabotegravir pharmacokinetics was best described using a one‐compartment model with distinct first order‐absorption for oral and intramuscular administrations, and identical volume and clearance. Our model showed almost 40% faster absorption and 30% higher clearance than previously reported, resulting in a time to steady‐state of 8 months and an elimination half‐life of 4.6 weeks for long‐acting cabotegravir. Sex and body mass index significantly influenced absorption, and bodyweight affected clearance. Model‐based simulations showed that cabotegravir trough concentrations in females were 25% lower 4 weeks after the intramuscular loading dose, but 42% higher during the late maintenance phase. Finally, simulations indicated that in females, despite significantly higher cabotegravir concentrations, longer intervals between injections may not consistently ensure levels above the 4‐fold protein‐adjusted 90% inhibitory target concentration. [ABSTRACT FROM AUTHOR]

Background: The burden of herpes zoster (shingles) virus and associated complications, such as post-herpetic neuralgia, is higher in older adults and has a significant impact on quality of life. The incidence of herpes zoster and post-herpetic neuralgia is increased in people living with HIV (PLWH) compared to an age-matched general population, including PLWH on long-term antiretroviral therapy (ART) with no detectable viremia and normal CD4 counts. PLWH – even on effective ART may- exhibit sustained immune dysfunction, as well as defects in cells involved in the response to vaccines. In the context of herpes zoster, it is therefore important to assess the immune response to varicella zoster virus vaccination in older PLWH and to determine whether it significantly differs to that of HIV-uninfected healthy adults or younger PLWH. We aim at bridging these knowledge gaps by conducting a multicentric, international, non-randomised clinical study (SHINGR'HIV) with prospective data collection after vaccination with an adjuvant recombinant zoster vaccine (RZV) in two distinct populations: in PLWH on long-term ART (> 10 years) over 50 years of and age/gender matched controls. Methods: We will recruit participants from two large established HIV cohorts in Switzerland and in France in addition to age-/gender-matched HIV-uninfected controls. Participants will receive two doses of RZV two months apart. In depth-evaluation of the humoral, cellular, and innate immune responses and safety profile of the RZV will be performed to address the combined effect of aging and potential immune deficiencies due to chronic HIV infection. The primary study outcome will compare the geometric mean titer (GMT) of gE-specific total IgG measured 1 month after the second dose of RZV between different age groups of PLWH and between PLWH and age-/gender-matched HIV-uninfected controls. Discussion: The SHINGR'HIV trial will provide robust data on the immunogenicity and safety profile of RZV in older PLWH to support vaccination guidelines in this population. Trial registration: ClinicalTrials.gov NCT05575830. Registered on 12 October 2022. Eu Clinical Trial Register (EUCT number 2023-504482-23-00). [ABSTRACT FROM AUTHOR]

Background The immunogenicity of the standard influenza vaccine is reduced in solid-organ transplant (SOT) recipients, so new vaccination strategies are needed in this population. Methods Adult SOT recipients from 9 transplant clinics in Switzerland and Spain were enrolled if they were >3 months after transplantation. Patients were randomized (1:1:1) to a MF59-adjuvanted or a high-dose vaccine (intervention), or a standard vaccine (control), with stratification by organ and time from transplant. The primary outcome was vaccine response rate, defined as a ≥4-fold increase of hemagglutination-inhibition titers to at least 1 vaccine strain at 28 days postvaccination. Secondary outcomes included polymerase chain reaction–confirmed influenza and vaccine reactogenicity. Results A total of 619 patients were randomized, 616 received the assigned vaccines, and 598 had serum available for analysis of the primary endpoint (standard, n = 198; MF59-adjuvanted, n = 205; high-dose, n = 195 patients). Vaccine response rates were 42% (84/198) in the standard vaccine group, 60% (122/205) in the MF59-adjuvanted vaccine group, and 66% (129/195) in the high-dose vaccine group (difference in intervention vaccines vs standard vaccine, 0.20; 97.5% confidence interval [CI],.12–1); P <.001; difference in high-dose vs standard vaccine, 0.24 [95% CI,.16–1]; P <.001; difference in MF59-adjuvanted vs standard vaccine, 0.17 [97.5% CI,.08–1]; P <.001). Influenza occurred in 6% of the standard, 5% in the MF59-adjuvanted, and 7% in the high-dose vaccine groups. Vaccine-related adverse events occurred more frequently in the intervention vaccine groups, but most of the events were mild. Conclusions In SOT recipients, use of an MF59-adjuvanted or a high-dose influenza vaccine was safe and resulted in a higher vaccine response rate. Clinical Trials Registration Clinicaltrials.gov NCT03699839. [ABSTRACT FROM AUTHOR]

Sensory stimulation evokes a local, vasodilation-mediated blood flow increase to the activated brain region, which is referred to as functional hyperemia. Spontaneous vasomotion is a change in arteriolar diameter that occurs without sensory stimulation, at low frequency (∼0.1 Hz). These vessel diameter changes are a driving force for perivascular soluble waste clearance, the failure of which has been implicated in neurodegenerative disease. Stimulus-evoked vascular reactivity is known to propagate along penetrating arterioles to pial arterioles, but it is unclear whether spontaneous vasomotion propagates similarly. We therefore imaged both stimulus-evoked and spontaneous changes in pial arteriole diameter in awake, head-fixed mice with 2-photon microscopy. By cross-correlating different regions of interest (ROIs) along the length of imaged arterioles, we assessed vasomotion propagation. We found that both during rest and during visual stimulation, one-third of the arterioles showed significant propagation (i.e., a wave), with a median (interquartile range) wave speed of 405 (323) µm/s at rest and 345 (177) µm/s during stimulation. In a second group of mice, with GCaMP expression in their vascular smooth muscle cells, we also found spontaneous propagation of calcium signaling along pial arterioles. In summary, we demonstrate that spontaneous vasomotion propagates along pial arterioles like stimulus-evoked vascular reactivity. [ABSTRACT FROM AUTHOR]

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a multifaceted disease potentially responsible for various clinical manifestations including gastro-intestinal symptoms. Several evidences suggest that the intestine is a critical site of immune cell development, gut microbiota could therefore play a key role in lung immune response. We designed a monocentric longitudinal observational study to describe the gut microbiota profile in COVID-19 patients and compare it to a pre-existing cohort of ventilated non-COVID-19 patients. Methods: From March to December 2020, we included patients admitted for COVID-19 in medicine (43 not ventilated) or intensive care unit (ICU) (14 ventilated) with a positive SARS-CoV-2 RT-PCR assay in a respiratory tract sample. 16S metagenomics was performed on rectal swabs from these 57 COVID-19 patients, 35 with one and 22 with multiple stool collections. Nineteen non-COVID-19 ICU controls were also enrolled, among which 14 developed ventilator-associated pneumonia (pneumonia group) and five remained without infection (control group). SARS-CoV-2 viral loads in fecal samples were measured by qPCR. Results: Although similar at inclusion, Shannon alpha diversity appeared significantly lower in COVID-19 and pneumonia groups than in the control group at day 7. Furthermore, the microbiota composition became distinct between COVID-19 and non-COVID-19 groups. The fecal microbiota of COVID-19 patients was characterized by increased Bacteroides and the pneumonia group by Prevotella. In a distance-based redundancy analysis, only COVID-19 presented significant effects on the microbiota composition. Moreover, patients in ICU harbored increased Campylobacter and decreased butyrate-producing bacteria, such as Lachnospiraceae, Roseburia and Faecalibacterium as compared to patients in medicine. Both the stay in ICU and patient were significant factors affecting the microbiota composition. SARS-CoV-2 viral loads were higher in ICU than in non-ICU patients. Conclusions: Overall, we identified distinct characteristics of the gut microbiota in COVID-19 patients compared to control groups. COVID-19 patients were primarily characterized by increased Bacteroides and decreased Prevotella. Moreover, disease severity showed a negative correlation with butyrate-producing bacteria. These features could offer valuable insights into potential targets for modulating the host response through the microbiota and contribute to a better understanding of the disease's pathophysiology. Trial registration: CER-VD 2020–00755 (05.05.2020) & 2017–01820 (08.06.2018). [ABSTRACT FROM AUTHOR]

Balanites aegyptiaca is a valuable resource for local African populations. However, this natural resource is managed in an irrational and abusive way by local communities. In order to contribute to the enhancement and sustainable management of B. aegyptiaca, an approach combining two methods has been adopted. The first is based on an ethnobotanical survey relating to local knowledge of B. aegyptiaca products and the second is focused on the surface survey in 4 Divisions of the Far North Region of Cameroon. In total, 400 people aged at least 15 years were chosen according to their knowledge of B. aegyptiaca, ie 100 people in each Division. The experimental design is a split-plot (4 x 4), then Sub-Divisions (Kalfou, Mindif, Moutourwa and Pette) constitute the main treatment. B. aegyptiaca is an agroforestry species that plays a very important role in the life of local communities. The main products used are leaves (100%), fruits (98.19%) and seeds (90.06%). They are used mainly in consumption (98.19%) and marketing (91.67%). Garawa Park in Moutourwa Sub-Division is the richest in taxonomic diversity, with 20 species, divided into 14 genera and 11 families. On the other hand, B. aegyptiaca park of Ourosambo located in Kalfou Division is the least diversified with 9 species, divided into 7 genera and 6 families. The other parks show intermediate specific diversity, with the number of species varying from 10 species (Doyang) to 18 species (Toutka). The Shannon diversity index varies in the parks from 1.77 bit (Ourosambo) to 2.86 bit (Maoudine). Parkland vegetation has an "L" structure based on crown diameter and diameter at breast height (DBH). Depending on the heights, the vegetation presents an inverted "U" structure. These results could serve as a reference for the elaboration of strategies for the development and sustainable management of B. aegyptiaca parks in the Sudano-Sahelian zone of Cameroon. [ABSTRACT FROM AUTHOR]

Background: We previously reported an increase in meropenem prescriptions for Pseudomonas aeruginosa infections in our hospital after the implementation of the 10th version of the EUCAST breakpoints table for P. aeruginosa in January 2020. As a consequence, antibiotic susceptibility testing results were adapted by masking meropenem for P. aeruginosa isolates susceptible to either ceftazidime, cefepime or piperacillin-tazobactam. We aimed to assess the changes in meropenem prescriptions after the implementation of the selective reporting. Methods: In this retrospective single-centre observational study, we analysed antimicrobial therapies prescribed for P. aeruginosa infections after the susceptibility testing results have been made available over three periods: "before EUCAST update", "after EUCAST update without selective reporting" and "after EUCAST update with selective reporting", at Lausanne University Hospital, Switzerland. We collected epidemiological, microbiological and clinical data. The primary outcome was the prescription of meropenem to treat P. aeruginosa infections after the release of susceptibility testing results. Secondary outcomes were the use of increased dosage of non-meropenem anti-pseudomonal drugs, and IDs' consultations rates after the release of susceptibility testing results. Results: Among the 457 patients included, 65 (14.2%) received meropenem: 5/148 (3.4%) before EUCAST update, 51/202 (25.3%) after EUCAST update without selective reporting, and 9/107 (8.4%) after EUCAST update with selective reporting. Supervision and counselling from IDs as well as the use of increased dosages of non-carbapenem antibiotics increased in both periods after EUCAST update, compared to the first period, respectively: 40.5% (60/148) versus 61.4% (124/202) versus 51.4% (55/107) (P < 0.001), and 57.9% (84/148) versus 91.1% (183/202) versus 90.7% (97/107) (P < 0.001). Conclusions: Selective reporting of antibiotic susceptibility testing results might decrease unnecessary meropenem prescriptions for the treatment of P. aeruginosa infections and could be part of multimodal antibiotic stewardship interventions. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is characterized by progressive memory loss and cognitive decline. These impairments correlate with early alterations in neuronal network activity in AD patients. Disruptions in the activity of individual neurons have been reported in mouse models of amyloidosis. However, the impact of amyloid pathology on the spontaneous activity of distinct neuronal types remains unexplored in vivo. Here we use in vivo calcium imaging with multiphoton microscopy to monitor and compare the activity of excitatory and two types of inhibitory interneurons in the cortices of APP/PS1 and control mice under isoflurane anesthesia. We also determine the relationship between amyloid accumulation and the deficits in spontaneous activity in APP/PS1 mice. We show that somatostatin-expressing (SOM) interneurons are hyperactive, while parvalbumin-expressing interneurons are hypoactive in APP/PS1 mice. Only SOM interneuron hyperactivity correlated with proximity to amyloid plaque. These inhibitory deficits were accompanied by decreased excitatory neuron activity in APP/PS1 mice. Our study identifies cell-specific neuronal firing deficits in APP/PS1 mice driven by amyloid pathology. These findings highlight the importance of addressing the complexity of neuron-specific deficits to ameliorate circuit dysfunction in Alzheimer's disease. Interneuron-specific lines reveal that somatostatin interneurons are hyperactive whereas pyramidal neurons and PV interneurons are 'hypoactive' in the APP/PS1 mouse model of Alzheimer's Disease. [ABSTRACT FROM AUTHOR]

SHCS#879 is an ongoing Switzerland-wide multicenter observational study conducted within the Swiss HIV Cohort Study (SHCS) for the prospective follow-up of people living with HIV (PLWH) receiving long-acting injectable cabotegravir-rilpivirine (LAI-CAB/RPV). All adults under LAI-CAB/RPV and part of SHCS are enrolled in the project. The study addresses an integrated strategy of treatment monitoring outside the stringent frame of controlled clinical trials, based on relevant patient characteristics, clinical factors, potential drug-drug interactions, and measurement of circulating blood concentrations. So far, 91 blood samples from 46 PLWH have been collected. Most individuals are less than 50 years old, with relatively few comorbidities and comedications. The observed concentrations are globally in accordance with the available values reported in the randomized clinical trials. Yet, low RPV concentrations not exceeding twice the reported protein-adjusted 90% inhibitory concentration have been observed. Data available at present confirm a considerable between-patient variability overall. Based on the growing amount of PK data accumulated during this ongoing study, population pharmacokinetic analysis will characterize individual concentration-time profiles of LAI-CAB/RPV along with their variability in a real-life setting and their association with treatment response and tolerability, thus bringing key data for therapeutic monitoring and precision dosage adjustment of this novel long-acting therapy. [ABSTRACT FROM AUTHOR]

Background: After mild COVID-19, some outpatients experience persistent symptoms. However, data are scarce and prospective studies are urgently needed. Objectives: To characterize the post-COVID-19 syndrome after mild COVID-19 and identify predictors. Participants: Outpatients with symptoms suggestive of COVID-19 with (1) PCR-confirmed COVID-19 (COVID-positive) or (2) SARS-CoV-2 negative PCR (COVID-negative). Design: Monocentric cohort study with prospective phone interview between more than 3 months to 10 months after initial visit to the emergency department and outpatient clinics. Main Measures: Data of the initial visits were extracted from the electronic medical file. Predefined persistent symptoms were assessed through a structured phone interview. Associations between long-term symptoms and PCR results, as well as predictors of persistent symptoms among COVID-positive, were evaluated by multivariate logistic regression adjusted for age, gender, smoking, comorbidities, and timing of the survey. Key Results: The study population consisted of 418 COVID-positive and 89 COVID-negative patients, mostly young adults (median age of 41 versus 36 years in COVID-positive and COVID-negative, respectively; p = 0.020) and healthcare workers (67% versus 82%; p = 0.006). Median time between the initial visit and the phone survey was 150 days in COVID-positive and 242 days in COVID-negative patients. Persistent symptoms were reported by 223 (53%) COVID-positive and 33 (37%) COVID-negative patients (p = 0.006) and proportions were stable among the periods of the phone interviews. Overall, 21% COVID-positive and 15% COVID-negative patients (p = 0.182) attended care for this purpose. Four surveyed symptoms were independently associated with COVID-19: fatigue (adjusted odds ratio 2.14, 95% CI 1.04–4.41), smell/taste disorder (26.5, 3.46–202), dyspnea (2.81, 1.10–7.16), and memory impairment (5.71, 1.53–21.3). Among COVID-positive, female gender (1.67, 1.09–2.56) and overweight/obesity (1.67, 1.10–2.56) were predictors of persistent symptoms. Conclusions: More than half of COVID-positive outpatients report persistent symptoms up to 10 months after a mild disease. Only 4 of 14 symptoms were associated with COVID-19 status. The symptoms and predictors of the post-COVID-19 syndrome need further characterization as this condition places a significant burden on society. [ABSTRACT FROM AUTHOR]

Background: The characteristics and outcomes of adult patients with respiratory syncytial virus (RSV) infection who require ICU admission are poorly defined. Although several studies in adults with RSV infection have been published in recent years, they did not focus specifically on patients with critical illness.Research Question: What are the characteristics and outcomes of adult patients in the ICU with RSV infection and how do they compare with those of patients in the ICU with influenza infection?Study Design and Methods: This retrospective, multicenter study in France and Belgium (17 sites) compared the characteristics and outcomes of adult patients in the ICU with RSV infection vs those with influenza infection between November 2011 and April 2018. Each patient with RSV infection was matched by institution and date of diagnosis with a patient with influenza infection. In-hospital mortality was compared between the two groups, with adjustment for prognostic factors in a multivariate model (sex, age, main underlying conditions, and concurrent bloodstream infection).Results: Data from 618 patients (309 with RSV infection and 309 with influenza infection) were analyzed. Patients with RSV infection were significantly more likely to have an underlying chronic respiratory condition (60.2% vs 40.1%; P < .001) and to be immunocompromised (35% vs 26.2%; P = .02) than patients with influenza infection. Several differences in clinical signs and biological data at diagnosis were found between the groups. In-hospital mortality was not significantly different between the two groups (23.9% in the RSV group vs 25.6% in the influenza group; P = .63), even after adjustment for prognostic factors in a multivariate model.Interpretation: Adult patients in the ICU with RSV infection differ from adult patients in the ICU with influenza in terms of comorbidities and characteristics at diagnosis. RSV infection was associated with high in-hospital mortality, approaching 25%. In multivariate analysis, RSV infection was associated with a similar odds of in-hospital death compared with influenza infection. [ABSTRACT FROM AUTHOR]

Perivascular spaces (PVS) are compartments surrounding cerebral blood vessels that become visible on MRI when enlarged. Enlarged PVS (EPVS) are commonly seen in patients with cerebral small vessel disease (CSVD) and have been suggested to reflect dysfunctional perivascular clearance of soluble waste products from the brain. In this study, we investigated histopathological correlates of EPVS and how they relate to vascular amyloid-β (Aβ) in cerebral amyloid angiopathy (CAA), a form of CSVD that commonly co-exists with Alzheimer's disease (AD) pathology. We used ex vivo MRI, semi-automatic segmentation and validated deep-learning-based models to quantify EPVS and associated histopathological abnormalities. Severity of MRI-visible PVS during life was significantly associated with severity of MRI-visible PVS on ex vivo MRI in formalin fixed intact hemispheres and corresponded with PVS enlargement on histopathology in the same areas. EPVS were located mainly around the white matter portion of perforating cortical arterioles and their burden was associated with CAA severity in the overlying cortex. Furthermore, we observed markedly reduced smooth muscle cells and increased vascular Aβ accumulation, extending into the WM, in individually affected vessels with an EPVS. Overall, these findings are consistent with the notion that EPVS reflect impaired outward flow along arterioles and have implications for our understanding of perivascular clearance mechanisms, which play an important role in the pathophysiology of CAA and AD. [ABSTRACT FROM AUTHOR]

Introduction: Being able to quantify the invasiveness of a surgical procedure is important to weigh up its associated risks, since invasiveness governs the blood loss, operative time and likelihood of complications. Mirza et al. (Spine (Phila Pa 1976) 33:2651-2661, 2008) published an invasiveness index for spinal surgery. We evaluated the validity of a modified version of the Mirza invasiveness index (mMII), adapted for use with registry data.Methods: A cross-sectional analysis was performed with data acquired from the Spine Tango registry including 21,634 patients. The mMII was calculated as the sum of six possible interventions on each vertebral level: decompression, fusion and stabilization either on anterior or posterior structures. The association between the mMII and blood loss, operative time and complications was evaluated using multiple regression, adjusting for possible confounders.Results: The mean (± SD) mMII was 3.9 ± 5.0 (range 0-40). A 1-point increase in the mMII was associated with an additional blood loss of 12.8% (95% CI 12.6-13.0; p < 0.001) and an increase of operative time of 10.4 min (95% CI 10.20-10.53; p < 0.001). The R2 for the blood loss model was of 43% and for operative time, 47%. The mean mMII was significantly (p < 0.001) higher in patients with surgical complications (4.5 ± 5.6) and general medical complications (6.5 ± 7.0) compared to those without (3.8 ± 4.9). Our results were comparable to those reported in the original publication of Mirza et al. CONCLUSION: The mMII appeared to be a valid measure of surgical invasiveness in our study population. It can be used in predictor models and to adjust for surgical case-mix when comparing outcomes in different studies or different hospitals/surgeons in a registry. [ABSTRACT FROM AUTHOR]

CADASIL is a NOTCH3-associated cerebral small vessel disease. A pathological ultrastructural disease hallmark is the presence of NOTCH3-protein containing deposits called granular osmiophilic material (GOM), in small arteries. How these GOM deposits develop over time and what their role is in disease progression is largely unknown. Here, we studied the progression of GOM deposits in humanized transgenic NOTCH3Arg182Cys mice, compared them to GOM deposits in patient material, and determined whether GOM deposits in mice are associated with a functional CADASIL phenotype. We found that GOM deposits are not static, but rather progress in ageing mice, both in terms of size and aspect. We devised a GOM classification system, reflecting size, morphology and electron density. Six-month-old mice showed mostly early stage GOM, whereas older mice and patient vessels showed predominantly advanced stage GOM, but also early stage GOM. Mutant mice did not develop the most severe GOM stage seen in patient material. This absence of end-stage GOM in mice was associated with an overall lack of histological vascular pathology, which may explain why the mice did not reveal functional deficits in cerebral blood flow, cognition and motor function. Taken together, our data indicate that GOM progress over time, and that new GOM deposits are continuously being formed. The GOM staging system we introduce here allows for uniform GOM deposit classification in future mouse and human studies, which may lead to more insight into a potential association between GOM stage and CADASIL disease severity, and the role of GOM in disease progression. [ABSTRACT FROM AUTHOR]

Coagulopathic bleeding during and after cardiac surgery is associated with increased morbidity and mortality. Viscoelastic testing is increasingly used instead of laboratory testing. Our aim was to compare a new viscoelastic point-of-care device, the Quantra® System, with thromboelastography and standard laboratory testing. After ethical approval and with written informed consent, we prospectively recruited adult patients undergoing urgent cardiac surgery at increased risk of bleeding. Clot time and clot stiffness values were compared before, during and after cardiopulmonary bypass. We prospectively recruited 52 patients, of whom 34 (65%) were transfused with red blood cells. Our usual transfusion thresholds for fibrinogen (1.5 g.l-1 ), platelets (100,000.μl-1 ), prothrombin time (20 s), activated partial thromboplastin time (48 s) and maximum amplitude on thromboelastography (50 mm) corresponded to Quantra values of fibrinogen clot stiffness 2.0 hPa, platelet clot stiffness 13.5 hPa, clot time 159 s, clot time 183 s and clot stiffness 17.0 hPa, respectively. These Quantra thresholds showed high negative predictive value for low platelets (platelet clot stiffness, 97.4%), prolonged activated partial thromboplastin time (clot time, 92.6%) and reduced maximum amplitude on thromboelastography (clot stiffness, 93.6%). The Quantra predicted clinical need for transfusion of platelets (area under the curve 0.71, p = 0.001) but all tests performed poorly at predicting the need for fresh frozen plasma transfusion. We have shown that point-of-care testing using the novel Quantra system provides useful data for guiding transfusion management. [ABSTRACT FROM AUTHOR]

We describe the underlying genetic cause of a novel Rett‐like phenotype accompanied by areflexia in three methyl‐CpG‐binding protein 2‐negative individuals from two unrelated families. Discovery analysis was performed using whole‐exome sequencing followed by Sanger sequencing for validation and segregation. Functional studies using short‐hairpin RNA for targeted gene knockdown were implemented by the transfection of mouse cultured primary hippocampal neurons and in vivo by in utero electroporation. All patients shared a common homozygous frameshift mutation (chr9:135073515, c.376dupT, p.(Ser126PhefsTer241)) in netrin‐G2 (NTNG2, NM_032536.3) with predicted nonsense‐mediated decay. The mutation fully segregated with the disease in both families. The knockdown of either NTNG2 or the related netrin‐G family member NTNG1 resulted in severe neurodevelopmental defects of neuronal morphology and migration. While NTNG1 has previously been linked to a Rett syndrome (RTT)‐like phenotype, this is the first description of a RTT‐like phenotype caused by NTNG2 mutation. Netrin‐G proteins have been shown to be required for proper axonal guidance during early brain development and involved in N‐methyl‐ d‐aspartate‐mediated synaptic transmission. Our results demonstrating that knockdown of murine NTNG2 causes severe impairments of neuronal morphology and cortical migration are consistent with those of RTT animal models and the shared neurodevelopmental phenotypes between the individuals described here and typical RTT patients. [ABSTRACT FROM AUTHOR]

The objective of this research was to evaluate the influence of radiotherapy on the osseointegration of oral implants in a canine model. After the extraction of all mandibular premolars and first and second molars, 11 male beagles were divided into 3 groups. The control group (3 dogs) received no radiation. The second group (4 dogs) was irradiated 4 weeks after implantation. The third group (4 dogs) was irradiated 8 weeks before implantation. Eight implants were placed in each dog, in an alternating pattern: 4 non-submerged ITI Bonefit titanium plasma spray-coated and 4 submerged Steri-Oss hydroxyapatite-coated. The irradiated dogs received 4.3 Gy daily for 10 days. After 6 months of osseointegration, the dogs were sacrificed and each hemimandible was dissected to isolate the implants. Quantification of the extent of the direct bone-implant contact was carried out by scanning electron microscopy backscattered electron images that reproduced each implant in its entirety, using a digitizing table connected to a computer. The results were expressed as a percentage of direct bone-implant contact versus total perimeter accessible to bone. The bone contact percentage for the control group was 87% for Steri-Oss implants and 69% for the ITI Bonefit implants; for the animals irradiated after implantation, the percentages were 82 for Steri-Oss implants and 58 for ITI Bonefit implants; and for the animals irradiated before implantation, the percentages were 62 for Steri-Oss implants and 28 for ITI Bonefit implants. A statistically significant difference appeared between the 2 types of implants (P < .001). A statistically significant difference was also seen between the 3 groups for both types of implants, except between the control group and the group irradiated after implantation (P = .14). This indicates that, overall, the timing of irradiation influences osseointegration. Osseointegration is possible before and after radiotherapy; however, the direct bone-implant contact increased when the implants were placed before irradiation. [ABSTRACT FROM AUTHOR]

Anaemia in surgical patients is a common and serious problem; around 40% of patients presenting for major surgery are anaemic. Patients with pre-operative anaemia have significantly higher rates of morbidity and mortality and are likely to be transfused red cells. In addition, red cell transfusions are independently associated with worse outcomes. Pre-optimisation of anaemia in surgical patients leads to higher pre-operative haemoglobin concentrations and less need for transfusion. Patients undergoing major surgery (defined as blood loss > 500 ml expected or possible) should be optimised if their haemoglobin concentration is less than 130 g.l-1 on screening. Detection of anaemia should follow listing for surgery as soon as possible to allow enough time for optimisation. The most common cause of pre-operative anaemia is iron deficiency, which can be treated with iron therapy. Iron clinics should be set up in either primary or secondary care to allow for optimal treatment. In this review, we present literature supporting the optimisation of pre-operative anaemia and propose a treatment algorithm. [ABSTRACT FROM AUTHOR]

Purpose: Investigation of adverse events associated with anesthetic procedures is a method of quality control that identifies topics to improve clinical care and patient safety. Most research to date has been based on closed claim registries and anonymous reports which have specific limitations. Therefore, to evaluate a hospital's reporting system, the present study was designed to describe critical incidents that anesthesiologists voluntarily and non-anonymously reported through an anesthesia information management system.Methods: This is a historical observational cohort study on patients (age > 18 yr) undergoing anesthetic procedures in a tertiary referral hospital. A 20-item list of complications, as developed by the Netherlands Society of Anesthesiologists, was prospectively completed for each procedure. All critical incidents registered in the anesthesia information management system were then reclassified into 95 different critical incidents in a reproducible way.Results: There were 110,310 procedures performed in 65,985 patients, and after excluding 158 reports that did not depict a critical incident, 3,904 critical incidents in 3,807 (3.5%) anesthetic procedures remained. Technical difficulties with regional anesthesia (n = 445; 40 per 10,000 anesthetics; 95% confidence interval [CI], 36 to 44), hypotension (n = 432; 39 per 10,000 anesthetics; 95% CI, 35 to 43), and unexpected difficult intubation (n = 216; 20 per 10,000 anesthetics; 95% CI, 18 to 23) were the most frequently documented critical incidents.Conclusion: Accurate measurement and monitoring of critical incidents is crucial for patient safety. Despite the risk of underreporting and probable misclassification of manual reporting systems, our results give a comprehensive overview on the occurrence of voluntarily reported anesthesia-related critical incidents. This overview can direct development of a new reporting system and preventive strategies to decrease the future occurrence of critical incidents. [ABSTRACT FROM AUTHOR]

Abstract: Hereditary cerebral hemorrhage with amyloidosis‐Dutch type (HCHWA‐D) is an early onset hereditary form of cerebral amyloid angiopathy (CAA) pathology, caused by the E22Q mutation in the amyloid β (Aβ) peptide. Transforming growth factor β1 (TGFβ1) is a key player in vascular fibrosis and in the formation of angiopathic vessels in transgenic mice. Therefore, we investigated whether the TGFβ pathway is involved in HCHWA‐D pathogenesis in human postmortem brain tissue from frontal and occipital lobes. Components of the TGFβ pathway were analyzed with quantitative RT‐PCR. TGFβ1 and TGFβ Receptor 2 (TGFBR2) gene expression levels were significantly increased in HCHWA‐D in comparison to the controls, in both frontal and occipital lobes. TGFβ‐induced pro‐fibrotic target genes were also upregulated. We further assessed pathway activation by detecting phospho‐SMAD2/3 (pSMAD2/3), a direct TGFβ down‐stream signaling mediator, using immunohistochemistry. We found abnormal pSMAD2/3 granular deposits specifically on HCHWA‐D angiopathic frontal and occipital vessels. We graded pSMAD2/3 accumulation in angiopathic vessels and found a positive correlation with the CAA load independent of the brain area. We also observed pSMAD2/3 granules in a halo surrounding occipital vessels, which was specific for HCHWA‐D. The result of this study indicates an upregulation of TGFβ1 in HCHWA‐D, as was found previously in AD with CAA pathology. We discuss the possible origins and implications of the TGFβ pathway deregulation in the microvasculature in HCHWA‐D. These findings identify the TGFβ pathway as a potential biomarker of disease progression and a possible target of therapeutic intervention in HCHWA‐D. [ABSTRACT FROM AUTHOR]

Anaemia is common before cardiac surgery and is associated with increased morbidity and mortality. The World Health Organization (WHO) definition of anaemia is lower for women than for men by 10 g.l-1 , potentially putting women at a disadvantage compared with men with regard to pre-operative optimisation. Our hypothesis was that women with borderline anaemia (defined by us as haemoglobin concentration 120-129 g.l-1 ) would have a higher rate of red cell transfusion, morbidity and mortality than non-anaemic women (haemoglobin ≥ 130 g.l-1 ). This retrospective observational study included all adult patients admitted for elective cardiac surgery from January 2013 to April 2016. During the study period, 1388 women underwent cardiac surgery. Pre-operatively, 333 (24%) had a haemoglobin level < 120 g.l-1 ; 408 (29%) 120-129 g.l-1 ; and 647 (47%) ≥ 130 g.l-1 . Compared with non-anaemic women, women with borderline anaemia were more likely to be transfused (68.6% vs. 44.5%; RR 1.5, 95%CI 1.4-1.7; p < 0.0001) and were transfused with more units of red cells, mean (SD) 1.8 (2.8) vs. 1.3 (3.0); p < 0.0001. Hospital length of stay was significantly longer in the borderline anaemia group compared with non-anaemic women, median (IQR [range]) 8 (6-12 [3-45]) vs. 7 (6-11 [4-60]); p = 0.0159. Short- and long-term postoperative survival was comparable in both groups. Borderline anaemia is associated with increased red cell transfusion and prolonged hospital stay. Future research should address whether correction of borderline anaemia results in improved outcomes. [ABSTRACT FROM AUTHOR]

The cerebral blood flow (CBF) is a potential biomarker for neurological disease. However, the arterial transit time (ATT) of the labeled blood is known to potentially affect CBF quantification. Furthermore, ATT could be an interesting biomarker in itself, as it may reflect underlying macro‐ and microvascular pathologies. Currently, no optimized magnetic resonance imaging (MRI) sequence exists to measure ATT in mice. Recently, time‐encoded labeling schemes have been implemented in rats and humans, enabling ATT mapping with higher signal‐to‐noise ratio (SNR) and shorter scan time than multi‐delay arterial spin labeling (ASL). In this study, we show that time‐encoded pseudo‐continuous arterial spin labeling (te‐pCASL) also enables transit time measurements in mice. As an optimal design that takes the fast blood flow in mice into account, time encoding with 11 sub‐boli of 50 ms is proposed to accurately probe the inflow of labeled blood. For perfusion imaging, a separate, traditional pCASL scan was employed. From the six studied brain regions, the hippocampus showed the shortest ATT (169 ± 11 ms) and the auditory/visual cortex showed the longest (284 ± 16 ms). Furthermore, ATT was found to be preserved in old wild‐type mice. In a mouse with an induced carotid artery occlusion, prolongation of ATT was shown. In conclusion, this study shows the successful implementation of te‐pCASL in mice, making it possible, for the first time, to measure ATT in mice in a time‐efficient manner. [ABSTRACT FROM AUTHOR]

Purpose: The three aims of this Spine Tango registry study of patients undergoing decompression for spinal stenosis were to: report the rate of dural tear (DT) stratified by treatment centre; find factors associated with an increased likelihood of incurring a DT; and compare treatment outcomes in relation to DT (none vs. repaired vs. unrepaired DT).Methods: Multivariate logistic regression was used to assess the association between DT and patient and treatment characteristics. Patient-rated and surgical outcomes were compared in patients with no DT, repaired DT, and unrepaired DT, while adjusting for case-mix.Results: DT occurred in 328/3254 (10.1%) of included patients. The rate for all 29 contributing hospitals was within 95% confidence intervals of the average. The likelihood of DT increased by 2% per year of age, 1.78 times with previous spine surgery, 1.67 for a minimally/less invasive surgery, 1.58 times with laminectomy, and 1.40, and 2.12 times for BMI 31-35, and >35 in comparison with BMI 26-30, respectively. The majority of DTs (272/328; 82.9%) were repaired. Repairing the DT was associated with a longer duration of surgery (p < 0.001). More patients with repaired than with unrepaired DTs were satisfied with treatment, but the difference was not statistically significant. There was no association between DT and patient-reported outcomes.Conclusion: The unadjusted rate of incidental DT during decompression for LSS was homogeneous across the participating centres and was associated with age, BMI, previous surgery at the same spinal level, minimally/less invasive surgery, and laminectomy. Non-repair of DTs had no negative association with treatment outcome; however, the unrepaired DTs may have been those that were smaller in size. [ABSTRACT FROM AUTHOR]

The generic approach of the Spine Tango documentation system, which uses web-based technologies, is a necessity for reaching a maximum number of participants. This, in turn, reduces the potential for customising the Tango according to the individual needs of each user. However, a number of possibilities still exist for tailoring the data collection processes to the user's own hospital workflow. One can choose between a purely paper-based set-up (with in-house scanning, data punching or mailing of forms to the data centre at the University of Bern) and completely paper-free online data entry. Many users work in a hybrid mode with online entry of surgical data and paper-based recording of the patients' perspectives using the Core Outcome Measures Index (COMI) questionnaires. Preoperatively, patients can complete their questionnaires in the outpatient clinic at the time of taking the decision about surgery or simply at the time of hospitalisation. Postoperative administration of patient data can involve questionnaire completion in the outpatient clinic, the handing over the forms at the time of discharge for their mailing back to the hospital later, sending out of questionnaires by post with a stamped addressed envelope for their return or, in exceptional circumstances, conducting telephone interviews. Eurospine encourages documentation of patient-based information before the hospitalisation period and surgeon-based information both before and during hospitalisation; both patient and surgeon data should be acquired for at least one follow-up, at a minimum of three to six months after surgery. In addition, all complications that occur after discharge, and their consequences should be recorded. [ABSTRACT FROM AUTHOR]

Lymphocoele is a rare and little known complication with only a handful of reports available. We report two cases of lymphocoele after anterior lumbar surgery that have occurred in two different centres and discuss diagnosis and management options. The first case is that of a 53-year-old male patient undergoing two level anterior lumbar interbody fusion (ALIF) for disabling back pain due to disc degeneration in the context of an old spondylodiscitis. He developed a large fluid mass postoperatively. Fluid levels of creatinin were low and intravenous urography ruled out a urinoma suggesting the diagnosis of a lymphocoele. Following two unsuccessful drainage attempts he underwent a laparoscopic marsupialization. The second case was that of a 32-year-old female patient developing a large fluid mass following a L5 corpectomy for a burst fracture. She was treated successfully with insertion of a vacuum drain during 7 days. Lymphocoele is a rare complication but should be suspected if fluid collects postoperatively following anterior lumbar spine procedures. Chemical analysis of the fluid can help in diagnosis. Modern treatment consists of laparoscopic marsupialization. Lymph vessel anatomy should be borne in mind while exposing the anterior lumbar spine. [ABSTRACT FROM AUTHOR]

Purpose: To compare patient outcomes and complication rates after different decompression techniques or instrumented fusion (IF) in lumbar spinal stenosis (LSS). Methods: The multicentre study was based on Spine Tango data. Inclusion criteria were LSS with a posterior decompression and pre- and postoperative COMI assessment between 3 and 24 months. 1,176 cases were assigned to four groups: (1) laminotomy ( n = 642), (2) hemilaminectomy ( n = 196), (3) laminectomy ( n = 230) and (4) laminectomy combined with an IF ( n = 108). Clinical outcomes were achievement of minimum relevant change in COMI back and leg pain and COMI score (2.2 points), surgical and general complications, measures taken due to complications, and reintervention on the index level based on patient information. The inverse propensity score weighting method was used for adjustment. Results: Laminotomy, hemilaminectomy and laminectomy were significantly less beneficial than laminectomy in combination with IF regarding leg pain (ORs with 95 % CI 0.52, 0.34-0.81; 0.25, 0.15-0.41; 0.44, 0.27-0.72, respectively) and COMI score improvement (ORs with 95 % CI 0.51, 0.33-0.81; 0.30, 0.18-0.51; 0.48, 0.29-0.79, respectively). However, the sole decompressions caused significantly fewer surgical (ORs with 95 % CI 0.42, 0.26-0.69; 0.33, 0.17-0.63; 0.39, 0.21-0.71, respectively) and general complications (ORs with 95 % CI 0.11, 0.04-0.29; 0.03, 0.003-0.41; 0.25, 0.09-0.71, respectively) than laminectomy in combination with IF. Accordingly, the likelihood of required measures was also significantly lower after laminotomy (OR 0.28, 95 % CI 0.17-0.46), hemilaminectomy (OR 0.28, 95 % CI 0.15-0.53) and after laminectomy (OR 0.39, 95 % CI 0.22-0.68) in comparison with laminectomy with IF. The likelihood of a reintervention was not significantly different between the treatment groups. Discussion: As already demonstrated in the literature, decompression in patients with LSS is a very effective treatment. Despite better patient outcomes after laminectomy in combination with IF, caution is advised due to higher rates of surgical and general complications and consequent required measures. Based on the current study, laminotomy or laminectomy, rather than hemilaminectomy, is recommendable for minimum relevant pain relief. [ABSTRACT FROM AUTHOR]

Purpose: Since the Spine Tango registry was founded over a decade ago it has become established internationally. An annual report has been produced using the same format as the SWEspine group to allow for first data comparisons between the two registries. Methods: Data was captured with the latest generation of surgery and follow-up forms. Also, the Core Outcome Measures Index (COMI) from interventions performed in the year 2012 with follow-up to June 2013 was analyzed. Groups of patients with the most common degenerative lumbar spine diseases and a single group of patients with degenerative cervical spine diseases were created. The demographics, risk factors, previous treatments, current treatment, short-term outcomes, patient satisfaction and complications were analyzed. Pre- and postoperative pain and function scores were derived from the COMI. Results: About 6,500 procedures were captured with Spine Tango in 2012. The definitions and composition of all the degenerative groups could not completely be matched between the two registries with the consequence that the age and sex distributions were partially different. Preoperative pain levels were similar. The short-term outcomes available did not allow for evaluation of the final result of surgical intervention. This will be possible with the longer term data in the next annual report. There was a distinct disparity in reported complication rates between surgeons and patients. Conclusions: This is a valuable first step in creating comparable reports for SWEspine and Spine Tango. The German spine registry may be able to collaborate in the future because of similar items and data structure as Spine Tango. There needs to be more work on understanding the harmonization of the different degenerative subgroups. The Spine Tango report is weakened by the short and incomplete follow-up. The visual presentation of data may be a useful model for aiding decision making for surgeons and patients in the future. [ABSTRACT FROM AUTHOR]

Background: Comparative effectiveness research in spine surgery is still a rarity. In this study, pain alleviation and quality of life (QoL) improvement after lumbar total disc arthroplasty (TDA) and anterior lumbar interbody fusion (ALIF) were anonymously compared by surgeon and implant. Methods: A total of 534 monosegmental TDAs from the SWISSspine registry were analyzed. Mean age was 42 years (19-65 years), 59 % were females. Fifty cases with ALIF were documented in the international Spine Tango registry and used as concurrent comparator group for the pain analysis. Mean age was 46 years (21-69 years), 78 % were females. The average follow-up time in both samples was 1 year. Comparison of back/leg pain alleviation and QoL improvement was performed. Unadjusted and adjusted probabilities for achievement of minimum clinically relevant improvements of 18 VAS points or 0.25 EQ-5D points were calculated for each surgeon. Results: Mean preoperative back pain decreased from 69 to 30 points at 1 year (ØΔ 39pts) after TDA, and from 66 to 27 points after ALIF (ØΔ 39pts). Mean preoperative QoL improved from 0.34 to 0.74 points at 1 year (ØΔ 0.40pts). There were surgeons with better patient selection, indicated by lower adjusted probabilities reflecting worsening of outcomes if they had treated an average patient sample. ALIF had similar pain alleviation than TDA. Conclusions: Pain alleviation after TDA and ALIF was similar. Differences in surgeon's patient selection based on pain and QoL were revealed. Some surgeons seem to miss the full therapeutic potential of TDA by selecting patients with lower symptom severity. [ABSTRACT FROM AUTHOR]

Indications for correction of post-traumatic kyphotic deformity of the spine and technical aspects of the surgical procedure are reviewed. Surgical correction of post-traumatic deformity of the spine should be considered in patients presenting a local excess of kyphosis in the fractured area superior to 20° with poor functional tolerance. Severe pain, explained by objective factors such as canal or neuroforamen compromise with or without peripheral symptoms, angular deformity, non-union, focal instability, adjacent painful compensatory deformity such as lumbar hyper-lordosis or thoracic hypo-kyphosis or lordosis is a further argument for surgery. More advanced age, litigation, work-related trauma are negative factors. Planning of the surgical procedure includes the choice of the approach(es), the corrective means: subtraction osteotomy or vertebral body reconstruction and the nature and extent of osteosynthesis and fusion. Decision-making factors includes: level of trauma, severity of deformity, history of previous surgery in the area of deformity, bone quality, age of fracture. Corrective surgery of a post-traumatic deformity of the spine is a difficult procedure that should be considered only by an experienced team, after careful consideration of the indication and with the consent of a well-informed patient. Complications do occur and lead to the need of re-intervention in up to 10% of our cases. However, significant complications with lasting consequences did not occur in our experience. The more severe is the deformity, the better are the chances to improve the patient, as long as the surgical goals are fulfilled. [ABSTRACT FROM AUTHOR]

The generic approach of the Spine Tango documentation system, which uses web-based technologies, is a necessity for reaching a maximum number of participants. This, in turn, reduces the potential for customising the Tango according to the individual needs of each user. However, a number of possibilities still exist for tailoring the data collection processes to the user’s own hospital workflow. One can choose between a purely paper-based set-up (with in-house scanning, data punching or mailing of forms to the data centre at the University of Bern) and completely paper-free online data entry. Many users work in a hybrid mode with online entry of surgical data and paper-based recording of the patients’ perspectives using the Core Outcome Measures Index (COMI) questionnaires. Preoperatively, patients can complete their questionnaires in the outpatient clinic at the time of taking the decision about surgery or simply at the time of hospitalisation. Postoperative administration of patient data can involve questionnaire completion in the outpatient clinic, the handing over the forms at the time of discharge for their mailing back to the hospital later, sending out of questionnaires by post with a stamped addressed envelope for their return or, in exceptional circumstances, conducting telephone interviews. Eurospine encourages documentation of patient-based information before the hospitalisation period and surgeon-based information both before and during hospitalisation; both patient and surgeon data should be acquired for at least one follow-up, at a minimum of three to six months after surgery. In addition, all complications that occur after discharge, and their consequences should be recorded. [ABSTRACT FROM AUTHOR]

British commercial and political hopes to expand trade in the new Soviet state after 1920 were to an extent disappointed. Despite successful ventures by individual companies, in aggregate business fell short of expectations, especially compared with German and American competitors. The reasons were both (micro and macro) economic variables and political factors, in Britain and the USSR. From 1926 the Soviet regime was committed to rapid industrialization and a pattern of imports in which Germany enjoyed some comparative advantage. But, in contrast to major rivals, British governments occasionally tried to use trade as a political instrument to the disadvantage of commercial operations. [ABSTRACT FROM AUTHOR]

Team games, initially and principally cricket but later other games, were played in mental asylums in various parts of Britain from the mid-nineteenth century, before being abandoned in the move to 'care in the community' from c. 1980s. Taking as a detailed example the Norfolk Lunatic Asylum (later St Andrew's Hospital), this article examines the use of games in patient therapy. Games were originally confined to male patients but later included women. Using archival and interview sources we assess the value of such therapy, the response of the patients and the demise of the idea before the final closure of the hospital. [ABSTRACT FROM AUTHOR]

Reconstruction of large anterior vertebral column defects is indicated in a number of pathological conditions including tumor, infection, trauma and post-traumatic deformity. Several substitutes and techniques are available for the functional restoration of the vertebral column. Vascularized bone transfers, autografts, allografts or xenografts have been used, as well as metal or ceramic implants. All of these bear potential advantages and drawbacks in terms of associated morbidity of graft harvesting, disease transmission, mechanical failure, implant incorporation and overall long-term clinical outcome. In the present paper we report our experience with the use of freeze-dried, gamma-irradiated, cortical allograft for the reconstruction of large, anterior segmental defects of the spine, involving at least one vertebral body with its two adjacent discs. Cortical allografts were used in 67 cases operated for a variety of conditions. No case of disease transmission, infection or long-term mechanical graft failure occurred in our entire series, with a mean follow-up of 31 months. Fusion and mechanical stability was reliably obtained. Specific advantages include the absence of donor site morbidity, the possibilities for exact trimming to the size of the defect, superior mechanical strength as compared to available autograft, and reliable fusion with the host bone with partial bone remodeling, preventing fatigue failure. We conclude that freeze-dried, irradiated cortical allografts are safe and effective for anterior reconstruction of the spine. [ABSTRACT FROM AUTHOR]

This article examines the sale of agricultural machinery to the Soviet Union before 1914 by the agricultural engineering company Ransomes Sims & Jeffries of Ipswich, England. Ransomes was one of the best-known agricultural engineering companies in the late nineteenth century and, unlike its then contemporaries, the firm is still in independent operation. After 1868 iron and steel products, including agricultural machinery, were admitted duty-free into the Soviet Union as part of a deliberate policy to stimulate agricultural production. There is no doubt that this provided some stimulus to the sale of British agricultural machinery in the Soviet Union, although there is no evidence that exporters ceased their activities when duties were reimposed later. Perhaps of greater importance was the advent of the depression in arable farming in Great Britain and other parts of western Europe. In the early years of this expansion the demand for machinery came mostly from large gentry farms; in the later years it was peasant demand, for ploughs in particular, which increased most.

Examines the resurgence of lotteries in Great Britain during the twentieth century, analyzing the government's policy towards this form of revenue. What led to the revival of gambling in Great Britain; Examination of the government's stance towards lotteries; Historical analysis of lotteries in Great Britain; Comparison of Great Britain's policy towards lotteries to that of other European countries and the United States.

Massive deep-frozen bone allografts were implanted in 13 patients after en bloc tumor resection. Patients were followed up for 14 months to 17 years. Most of the reconstructive procedures included a segmental bone allograft with knee or ankle fusion. Graft infections were the most critical complications in regard to the end results, finally requiring amputation in two cases. There were three stress fractures; two of which were successfully treated without further complication. Graft incorporation was assessed by bone scintimetry in four cases. Isotope uptake by the center of the graft was found to be superior to control bone segments at only 15 years after surgery. Two recovered allograft specimens were available for a microradiographic study. Creeping substitution was a very slow process, initiated at the outer surface of the graft and characterized at 2-3 years after implantation by large, incompletely filled osteons. The present investigation demonstrates that massive bone allografts are very slowly revascularized and are intimately anchored by the host bone. Provided that tumor control is effective and graft infection is avoided, reconstructive surgery with massive bone allografts represents a successful alternative to prosthetic implants in young adults with a long life expectancy. [ABSTRACT FROM AUTHOR]

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Gambling is big business in contemporary Great Britain. Betting shops are seen in every high street, bingo games occupy redundant cinemas, every national newspaper provides a racing service and news of football pools; many operate their own form of lottery. There have even been proposals that a lottery competition provide marginal finance for Great Britain's National Health Service. Yet for over a century government set its face against gambling, attempting through various measures to suppress what was regarded as a morally dubious activity. Through most of the nineteenth century the state steadily reduced and restricted open public gambling opportunities. It is a curiosity therefore that gambling in various forms not only survived as a social activity; it also prospered and developed as a commercial venture. Nowhere outside the British Isles did the entrepreneur of gambling so prosper. Bookmakers grew in number and scale of operation in Great Britain and Ireland in a manner and to an extent virtually unknown elsewhere. Gambling developed as a highly profitable business, the basis for commercial prosperity being high levels of turnover rather than excessive returns on capital. The profit-ability of major bookmaking firms attracted large holding companies to buy them; horse race betting provided the basis for Ladbrokes PLC and its extensive interests in hotels, holidays and various other branches of the leisure industry.