Southern Ocean drives multidecadal atmospheric CO2 rise during Heinrich Stadials.

The last glacial period was punctuated by cold intervals in the North Atlantic region that culminated in extensive iceberg discharge events. These cold intervals, known as Heinrich Stadials, are associated with abrupt climate shifts worldwide. Here, we present CO2 measurements from the West Antarctic Ice Sheet Divide ice core across Heinrich Stadials 2 to 5 at decadal-scale resolution. Our results reveal multi-decadal-scale jumps in atmospheric CO2 concentrations within each Heinrich Stadial. The largest magnitude of change (14.0 ± 0.8 ppm within 55 ± 10 y) occurred during Heinrich Stadial 4. Abrupt rises in atmospheric CO2 are concurrent with jumps in atmospheric CH4 and abrupt changes in the water isotopologs in multiple Antarctic ice cores, the latter of which suggest rapid warming of both Antarctica and Southern Ocean vapor source regions. The synchroneity of these rapid shifts points to wind-driven upwelling of relatively warm, carbon-rich waters in the Southern Ocean, likely linked to a poleward intensification of the Southern Hemisphere westerly winds. Using an isotope-enabled atmospheric circulation model, we show that observed changes in Antarctic water isotopologs can be explained by abrupt and widespread Southern Ocean warming. Our work presents evidence for a multi-decadal- to century-scale response of the Southern Ocean to changes in atmospheric circulation, demonstrating the potential for dynamic changes in Southern Ocean biogeochemistry and circulation on human timescales. Furthermore, it suggests that anthropogenic CO2 uptake in the Southern Ocean may weaken with poleward strengthening westerlies today and into the future.

Fasting vs no fasting prior to catheterisation laboratory procedures: the SCOFF trial.

BACKGROUND AND AIMS: Current guidelines recommend 6 hours of solid food and 2 hours of clear liquid fasting for patients undergoing cardiac procedures with conscious sedation. There are no data to support this practice, and previous single centre studies support the safety of removing fasting requirements. The objective of this study was to determine the non-inferiority of a no fasting strategy to fasting prior to cardiac catheterisation procedures which require conscious sedation. METHODS: This is a multicentre, investigator-initiated, non-inferiority randomised trial conduced in Australia with a prospective open label blinded endpoint design. Patients referred for coronary angiography, percutaneous coronary intervention or cardiac implantable electronic device (CIED) related procedures were enrolled. Patients were randomised 1:1 to fasting as normal (6 hours solid food and 2 hours clear liquid) or no fasting requirements (encouraged to have regular meals but not mandated to do so). Recruitment occurred from 2022 to 2023. The primary outcome was a composite of aspiration pneumonia, hypotension, hyperglycaemia and hypoglycaemia assessed with a Bayesian approach. Secondary outcomes included patient satisfaction score, new ventilation requirement (non-invasive and invasive), new intensive care unit admission, 30-day readmission, 30-day mortality, 30-day pneumonia. RESULTS: 716 patients were randomised with 358 in each group. Those in the fasting arm had significantly longer solid food fasting (13.2 versus 3.0 hours, Bayes factor >100 indicating extreme evidence of difference) and clear liquid fasting times (7.0 versus 2.4 hours, Bayes factor >100). The primary composite outcome occurred in 19.1% of patients in the fasting arm and 12.0% of patients in the no fasting arm. The estimate of the mean posterior difference in proportions in the primary composite outcome was -5.2% (95% CI -9.6 to -0.9, ) favouring no fasting. This result confirms non-inferiority (posterior probability >99.5%) and superiority (posterior probability 99.1%) of no fasting for the primary composite outcome. The no fasting arm had improved patient satisfaction scores with a posterior mean difference of 4.02 points (95% CI 3.36 to 4.67, Bayes factor >100). Secondary outcome events were similar. CONCLUSIONS: In patients undergoing cardiac catheterisation and CIED related procedures, no fasting was non-inferior and superior to fasting for the primary composite outcome of aspiration pneumonia, hypotension, hyperglycaemia and hypoglycaemia. Patient satisfaction scores were significantly better with no fasting. This supports removing fasting requirements for patients undergoing cardiac catheterisation laboratory procedures that require conscious sedation.

Use of 3D Anorectal Ultrasonography in the Preoperative Assessment of Complex Anal Fistulas and Patterns of Healing, Failure, and Recurrence After Ligation of the Intersphincteric Fistula Tract (LIFT).

OBJECTIVES: To use three-dimensional anorectal ultrasonography (3D-US) to evaluate the outcome of ligation of the intersphincteric fistula tract (LIFT) in patients with crypto-glandular transsphincteric fistula and describing the patterns of healing, failure, and recurrence rate. METHODS: After classifying the fistula and determining the length of the sphincter muscle to be transected, the patients were submitted to LIFT. The accuracy of pre- and postoperative 3D-US with 360° endoprobe (16 MHz) with automatic scanning and clinical findings was evaluated against surgical findings. Three outcomes were considered: healing, failure (persistent anal fistula through the original external opening or intersphincteric), and recurrence (reappearance of the anal fistula). RESULTS: Sixty-three patients of both sexes were evaluated. The 3D-US assessment revealed primary healing in 50 (79.3%) patients, although in 6 (9.5%) cases healing was delayed and the cavity was without communication with the anal canal. The procedure failed in 9 (15.9%) and fistula recurred in 4 (6.3%), all of whom underwent a second surgery based on a new 3D-US, resulting in a 92.3% (12/13) healing rate on 3D-US. CONCLUSIONS: A 3D-US was found to be useful in the preoperative assessment of fistulas by quantifying the percentage of muscle to be transected, and in the postoperative assessment by identifying healing, types of failure, and recurrence. The 3D-US was accurate and consistent with surgical findings.

Impact of early postoperative blood glucose variability on serum endocan level in cardiac surgery patients: a sub study of the ENDOLUNG observational study.

BACKGROUND: Early postoperative glycemic variability is associated with worse outcome after cardiac surgery, but the underlying mechanisms remain unknown. This study aimed to describe the relationship between postoperative glycemic variability and endothelial function, as assessed by serum endocan level in cardiac surgery patients. METHODS: We performed a post hoc analysis of patients included in the single-center observational ENDOLUNG study. Adult patients who underwent planned isolated coronary artery bypass graft surgery were eligible. Postoperative glycemic variability was assessed by calculating the coefficient of variability (CV) of blood glucose measured within 24 (CV24) and 48 (CV48) hours after surgery. Serum endocan level was measured at 24 (Endocan24) and 48 (Endocan48) hours after surgery. Pearson's correlation coefficient with 95% confidence interval (95% CI) was calculated between CV24 and Endocan24, and between CV48 and Endocan48. RESULTS: Data from 177 patients were analyzed. Median CV24 and CV48 were 18% (range 7 to 39%) and 20% (range 7 to 35%) respectively. Neither CV48 nor CV24 were significantly correlated to Endocan48 and Endocan24 respectively (r (95% CI) = 0.150 (0.001 to 0.290; and r (95% CI) = 0.080 (-0.070 to 0.220), respectively). CONCLUSIONS: Early postoperative glycemic variability within 48 h after planned cardiac surgery does not appear to be correlated with postoperative serum endocan level. CLINICAL TRIAL REGISTRATION NUMBER: NCT02542423.

Impact of Internal Anal Sphincter Division on Continence Disturbance in Female Patients.

BACKGROUND: Few studies measured the pre- and postoperative anatomic and functional anal canal using 3-dimensional endoanal ultrasound and anal manometry and correlated sphincter division with fecal incontinence, severity, and function. OBJECTIVE: To assess the incidence of fecal incontinence in patients who underwent internal anal sphincter division for anal fissure or intersphincteric anal fistula and correlate severity of symptoms with percentage of divided muscle, anatomical measurements, and anal pressures. DESIGN: Prospective cohort study. SETTINGS: Colorectal surgery unit, tertiary referral center. PATIENTS: Patients underwent clinical assessment using the Cleveland Clinic Florida Fecal Incontinence score for severity of symptoms, manometry, and ultrasound. MAIN OUTCOMES MEASURES: Ultrasound measurements of length, percentage, and angle of divided internal anal sphincter, anterior external anal sphincter, posterior external anal sphincter plus puborectalis, and gap lengths. RESULTS: Sixty-three women (mean age, 44 years) were divided into 2 groups: 30 (48%) underwent fistulotomy for intersphincteric anal fistula and 33 (52%) underwent sphincterotomy for chronic anal fissure with high anal resting pressure. Forty-six percent experienced some measure of fecal incontinence after internal anal sphincter division. Incidence of fecal incontinence, severity of symptoms, and angle of the divided internal anal sphincter were similar between the groups. Length and percentage of the divided internal anal sphincter were significantly higher in the intersphincteric anal fistula. External anal sphincter and external anal sphincter plus puborectalis lengths were similar in both groups. Gap length was significantly longer in chronic anal fissures with high anal resting pressure. LIMITATIONS: Single-institution, exclusion of males. CONCLUSIONS: Fecal incontinence was reported in half of the patients who underwent internal anal sphincter division. Despite the greater length and percentage of internal anal sphincter division in patients who underwent fistulotomy, incidence and severity of fecal incontinence were similar in both groups. Three-dimensional endoanal ultrasound showed greater gap length in the sphincterotomy group, which may be functionally significant after the division of the shorter internal anal sphincter but with a similar impact on fecal incontinence in both groups. IMPACTO DE LA DIVISIN DEL ESFNTER ANAL INTERNO EN LA ALTERACIN DE LA CONTINENCIA EN PACIENTES DE SEXO FEMENINO: ANTECEDENTES:Pocos estudios han medido el canal anal anatómico y funcional antes y después de la cirugía mediante ecografía endoanal tridimensional y manometría anal, y correlacionado la división del esfínter con la incontinencia fecal, la gravedad y la función.OBJETIVO:Evaluar la incidencia de incontinencia fecal en pacientes sometidos a división del esfínter anal interno por fisura anal o fístula anal interesfinteriana, y correlacionar la gravedad de los síntomas con el porcentaje de músculo dividido, las medidas anatómicas y las presiones anales.DISEÑO:Estudio de cohorte prospectivo.AJUSTE:Unidad de cirugía colorrectal, centro de referencia de tercer nivel.PACIENTES:Pacientes sometidos a una evaluación clínica utilizando la puntuación de incontinencia fecal de Cleveland Clinic Florida para la gravedad de los síntomas, la manometría y la ecografía.PRINCIPALES MEDIDAS DE RESULTADO:Mediciones por ultrasonido de la longitud, el porcentaje y el ángulo del esfínter anal interno dividido y el esfínter anal externo anterior, el esfínter anal externo posterior más el puborrectal y las longitudes del espacio.RESULTADOS:Sesenta y tres mujeres (edad media, 44 años) se dividieron en 2 grupos: 30 (48%) sometidos a fistulotomía por fístula anal interesfinteriana y 33 (52%) sometidos a esfinterotomía por fisura anal crónica con alta presión anal en reposo. El 46% experimentó algún grado de incontinencia fecal después de la división del esfínter anal interno. La incidencia de incontinencia fecal, la gravedad de los síntomas y el ángulo del esfínter anal interno dividido fueron similares entre los grupos. La longitud y el porcentaje del esfínter anal interno dividido fueron significativamente mayores en la fístula anal interesfinteriana. Las longitudes del esfínter anal externo y del esfínter anal externo más el puborrectal fueron similares en ambos grupos. La longitud del espacio fue significativamente mayor en la fisura anal crónica con alta presión anal en reposo.LIMITACIONES:Institución única, exclusión de varones.CONCLUSIÓN:La incontinencia fecal se reportó en la mitad de los pacientes sometidos a división del esfínter anal interno. A pesar de la mayor longitud y porcentaje de división del esfínter anal interno en los pacientes sometidos a fistulotomía, la incidencia y gravedad de la incontinencia fecal fue similar en ambos grupos. La ecografía endoanal tridimensional mostró una mayor longitud del espacio en el grupo de esfinterotomía, lo que puede ser funcionalmente significativo después de la división del esfínter anal interno más corto, pero con un impacto similar en la incontinencia fecal en ambos grupos. (Traducción-Dr. Fidel Ruiz Healy ).

High Physical Activity Volume Is Associated With an Increase in the Calibre of the Lower Limb Veins Without Impact on Functional Discomfort: the VARISPORT Study.

OBJECTIVE: The relationship between physical activity and lower limb veins is complex. If a sedentary lifestyle is considered to be negative on lower limb veins, specific information on physical activity varicose vein volume is sparse, especially the effect of high physical activity volume. The main objective of the VARISPORT study was to evaluate lower limb veins (clinically, morphologically, and haemodynamically) and chronic venous disease symptoms in subjects exposed to high physical activity volume compared with a group of non-exposed subjects. METHODS: A cross sectional study compared a group of high exercise training volume volunteers (more than eight hours of uninterrupted vigorous intensity physical activity per week for more than six months: high physical activity volume group, HPAV group) with a volunteer control group matched for age, sex, and body mass index. Clinical examination was performed to determine the Clinical, Etiological, Anatomical, Pathophysiological (CEAP) classification of each subject and the Carpentier score was used to assess symptoms related to possible chronic venous disease. Duplex ultrasonography was used to assess vein diameters and reflux in the deep and superficial veins. RESULTS: One hundred and nineteen subjects were included in each group. The lower limb veins (deep and superficial) were significantly more dilated in the HPAV group. More reflux was found in the great saphenous veins and non-saphenous veins in the HPAV group. High physical activity volume was associated with a higher frequency of visible varicose veins (stage C2 of the CEAP classification), odds ratio 3.37 (95% confidence interval 1.66 - 7.25) without impact on functional discomfort (44 subjects with a Carpentier score ≥ 1 in each group). CONCLUSION: The VARISPORT study reported an increase in the calibre of the lower limb veins without impact on functional discomfort. Further studies are needed to determine whether these athletic veins are truly pathological varicose veins or simply an adaptation to high physical activity volumes.

Outer Hair Cell Glutamate Signaling through Type II Spiral Ganglion Afferents Activates Neurons in the Cochlear Nucleus in Response to Nondamaging Sounds.

Cochlear outer hair cells (OHCs) are known to uniquely participate in auditory processing through their electromotility, and like inner hair cells, are also capable of releasing vesicular glutamate onto spiral ganglion (SG) neurons: in this case, onto the sparse Type II SG neurons. However, unlike glutamate signaling at the inner hair cell-Type I SG neuron synapse, which is robust across a wide spectrum of sound intensities, glutamate signaling at the OHC-Type II SG neuron synapse is weaker and has been hypothesized to occur only at intense, possibly damaging sound levels. Here, we tested the ability of the OHC-Type II SG pathway to signal to the brain in response to moderate, nondamaging sound (80 dB SPL) as well as to intense sound (115 dB SPL). First, we determined the VGluTs associated with OHC signaling and then confirmed the loss of glutamatergic synaptic transmission from OHCs to Type II SG neurons in KO mice using dendritic patch-clamp recordings. Next, we generated genetic mouse lines in which vesicular glutamate release occurs selectively from OHCs, and then assessed c-Fos expression in the cochlear nucleus in response to sound. From these analyses, we show, for the first time, that glutamatergic signaling at the OHC-Type II SG neuron synapse is capable of activating cochlear nucleus neurons, even at moderate sound levels.SIGNIFICANCE STATEMENT Evidence suggests that cochlear outer hair cells (OHCs) release glutamate onto Type II spiral ganglion neurons only when exposed to loud sound, and that Type II neurons are activated by tissue damage. Knowing whether moderate level sound, without tissue damage, activates this pathway has functional implications for this fundamental auditory pathway. We first determined that OHCs rely largely on VGluT3 for synaptic glutamate release. We then used a genetically modified mouse line in which OHCs, but not inner hair cells, release vesicular glutamate to demonstrate that moderate sound exposure activates cochlear nucleus neurons via the OHC-Type II spiral ganglion pathway. Together, these data indicate that glutamate signaling at the OHC-Type II afferent synapse participates in auditory function at moderate sound levels.

Exploring Silent Speech Interfaces Based on Frequency-Modulated Continuous-Wave Radar.

Speech is our most natural and efficient form of communication and offers a strong potential to improve how we interact with machines. However, speech communication can sometimes be limited by environmental (e.g., ambient noise), contextual (e.g., need for privacy), or health conditions (e.g., laryngectomy), preventing the consideration of audible speech. In this regard, silent speech interfaces (SSI) have been proposed as an alternative, considering technologies that do not require the production of acoustic signals (e.g., electromyography and video). Unfortunately, despite their plentitude, many still face limitations regarding their everyday use, e.g., being intrusive, non-portable, or raising technical (e.g., lighting conditions for video) or privacy concerns. In line with this necessity, this article explores the consideration of contactless continuous-wave radar to assess its potential for SSI development. A corpus of 13 European Portuguese words was acquired for four speakers and three of them enrolled in a second acquisition session, three months later. Regarding the speaker-dependent models, trained and tested with data from each speaker while using 5-fold cross-validation, average accuracies of 84.50% and 88.00% were respectively obtained from Bagging (BAG) and Linear Regression (LR) classifiers, respectively. Additionally, recognition accuracies of 81.79% and 81.80% were also, respectively, achieved for the session and speaker-independent experiments, establishing promising grounds for further exploring this technology towards silent speech recognition.

Infectious Complications of Biological and Small Molecule Targeted Immunomodulatory Therapies.

The past 2 decades have seen a revolution in our approach to therapeutic immunosuppression. We have moved from relying on broadly active traditional medications, such as prednisolone or methotrexate, toward more specific agents that often target a single receptor, cytokine, or cell type, using monoclonal antibodies, fusion proteins, or targeted small molecules. This change has transformed the treatment of many conditions, including rheumatoid arthritis, cancers, asthma, and inflammatory bowel disease, but along with the benefits have come risks. Contrary to the hope that these more specific agents would have minimal and predictable infectious sequelae, infectious complications have emerged as a major stumbling block for many of these agents. Furthermore, the growing number and complexity of available biologic agents makes it difficult for clinicians to maintain current knowledge, and most review articles focus on a particular target disease or class of agent. In this article, we review the current state of knowledge about infectious complications of biologic and small molecule immunomodulatory agents, aiming to create a single resource relevant to a broad range of clinicians and researchers. For each of 19 classes of agent, we discuss the mechanism of action, the risk and types of infectious complications, and recommendations for prevention of infection.

The Prevalence of Iron Deficiency in Atrial Fibrillation: Low Hanging Fruit?

Background and Objectives: Atrial fibrillation (AF) is the most common sustained arrhythmia worldwide. The relationship between AF and iron deficiency is poorly understood. Materials and Methods: We conducted an observational study investigating the prevalence of iron deficiency in those with AF. Iron deficiency was defined by the American College of Cardiology (ACC) criteria for iron deficiency in heart failure. Results: Of 134 eligible subjects, 81 (60.4%) met the ACC definition of iron deficiency in heart failure. Those who were iron deficient were more likely to be female (OR 1.876, p = 0.005), have a history of diabetes mellitus (OR 3.085, p = 0.001) a history of stroke (OR 3.147, p = 0.016), and have higher CHA2DS2-VASc (p ≤ 0.0001) and Charlson Comorbidity Index scores (CCI) (p = 0.007). Conclusions: The prevalence of iron deficiency in those with AF appears high and warrants evaluation in a prospective study.