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Whipple’s disease (WD) is a rare infectious disease with a wide clinical spectrum. Associated thrombotic manifestations are not well described in WD, only related to ‘stroke-like syndrome’. We present a case of a 39-year-old man with a 1-year history of self-limited episodes of fever, associated with generalised adenopathies and recurrent superficial and deep venous thrombosis events, which have resorted four times despite the anticoagulant treatment. Finally, the patient is diagnosed with WD. Following treatment the patient improved in his general condition, and no more episodes of fever neither thrombosis appeared during a follow-up of more than 3 years.

Reported neuro-modulation schemes in the literature are typically classified as closed-loop or open-loop. A novel group of recently developed neuro-modulation devices may be better described as a neural bypass, which attempts to transmit neural data from one location of the nervous system to another. The most common form of neural bypasses in the literature utilize EEG recordings of cortical information paired with functional electrical stimulation for effector muscle output, most commonly for assistive applications and rehabilitation in spinal cord injury or stroke. Other neural bypass locations that have also been described, or may soon be in development, include cortical-spinal bypasses, cortical-cortical bypasses, autonomic bypasses, peripheral-central bypasses, and inter-subject bypasses. The most common recording devices include EEG, ECoG, and microelectrode arrays, while stimulation devices include both invasive and noninvasive electrodes. Several devices are in development to improve the temporal and spatial resolution and biocompatibility for neuronal recording and stimulation. A major barrier to entry includes neuroplasticity and current decoding mechanisms that regularly require retraining. Neural bypasses are a unique class of neuro-modulation. Continued advancement of neural recording and stimulating devices with high spatial and temporal resolution, combined with decoding mechanisms uninhibited by neuroplasticity, can expand the therapeutic capability of neural bypassing. Overall, neural bypasses are a promising modality to improve the treatment of common neurologic disorders, including stroke, spinal cord injury, peripheral nerve injury, brain injury and more.

OBJECTIVE Maximal safe ablation of target structures during magnetic resonance–guided laser interstitial thermal therapy (MRgLiTT) is critical to achieving good seizure outcome in patients with mesial temporal lobe epilepsy (mTLE). The authors sought to determine whether intraoperative physiological variables are associated with ablation volume during MRgLiTT. METHODS Patients with mTLE who underwent MRgLiTT at our institution from 2014 to 2019 were retrospectively analyzed. Ablation volume was determined with volumetric analysis of intraoperative postablation MR images. Physiological parameters (systolic blood pressure [SBP], diastolic blood pressure [DBP], mean arterial pressure [MAP], end-tidal carbon dioxide [ETCO2]) measured 40 minutes prior to ablation were analyzed. Univariate and multivariate regression analyses were performed to determine independent predictors of ablation volume. RESULTS Forty-four patients met the inclusion criteria. The median (interquartile range) ablation volume was 4.27 (2.92–5.89) cm3, and median ablation energy was 7216 (6402–8784) J. The median MAP, SBP, DBP, and ETCO2 values measured during the 40-minute period leading up to ablation were 72.8 (66.2–81.5) mm Hg, 104.4 (96.4–114.4) mm Hg, 62.4 (54.1–69.8) mm Hg, and 34.1 (32.0–36.2) mm Hg, respectively. In univariate analysis, only total laser energy (r = 0.464, p = 0.003) and 40-minute average ETCO2 (r = −0.388, p = 0.012) were significantly associated with ablation volume. In multivariate analysis, only ETCO2 ≤ 33 mm Hg (p = 0.001) was significantly associated with ablation volume. CONCLUSIONS Total ablation energy and ETCO2, but not blood pressure, may significantly affect ablation volume in mTLE patients undergoing MRgLiTT. Mild hypocapnia was associated with increased extent of ablation. Intraoperative monitoring and modulation of ETCO2 may help improve extent of ablation, prediction of ablation volume, and potentially seizure outcome.

Modulation of the immune system to prevent lung injury is being widely used against the new coronavirus disease (COVID-19). The primary endpoint was mortality at 7 days after tocilizumab administration. Secondary endpoints were admission to the intensive care unit, development of ARDS and respiratory insufficiency among others.We report the preliminary results from the Vall d'Hebron cohort study at Vall d'Hebron University Hospital, in Barcelona (Spain), including all consecutive patients who had a confirmed SARS-CoV-2 infection and who were treated with tocilizumab until March 25th.82 patients with COVID-19 received at least one dose of tocilizumab. The mean (± SD) age was 59.1 (19.8) years, 63% were male, 22% were of non-Spanish ancestry, and the median (IQR) age-adjusted Charlson index at baseline was 3 (1-4) points. Respiratory failure and ARDS developed in 62 (75.6%) and 45 (54.9%) patients, respectively. Median time from symptom onset to ARDS development was 8 (5-11) days. Mortality at 7 days was 26.8%. Hazard ratio for mortality was 3.3; 95% CI, 1.3-8.5 (age-adjusted hazard ratio for mortality 2.1; 95% CI, 0.8-5.8) if tocilizumab was administered after the onset of ARDS.Early administration of tocilizumab in patients needing oxygen supplementation may be critical to patient recovery. Our preliminary data could inform bedside decisions until more data regarding the precise timing in of initiation of the treatment with tocilizumab.Los tratamientos inmunomoduladores para la prevención del daño pulmonar están siendo ampliamente estudiados contra la COVID-19. El objetivo primario es evaluar la mortalidad a los 7 días después de la administración de tocilizumab. El objetivo secundario es el ingreso en UCI, el desarrollo de distrés respiratorio agudo e insuficiencia respiratoria aguda entre otros.Informamos sobre los resultados preliminares de la cohorte del Hospital Universitario Vall d’Hebron en Barcelona (España), que incluye todos los pacientes consecutivos con infección confirmada por SARS-CoV-2 y que recibieron tratamiento con tocilizumab hasta el 25 de marzo 2020.Ochenta y dos pacientes con COVID-19 recibieron al menos una dosis de tocilizumab. La edad media (±DE) fue de 59,1 (±19,8) años, el 63% eran hombres, 22% correspondía a paciente nacidos fuera de España, y la mediana (RIC) del índice de Charlson ajustado por edad en el momento basal fue de 3 (1-4) puntos. Sesenta y dos pacientes (75,6%) y 45 pacientes (54,9%) desarrollaron insuficiencia respiratoria y distrés respiratorio agudo respectivamente. La mediana de tiempo desde el inicio de los síntomas hasta el desarrollo de ditrés fue de 8 días (5-11). La mortalidad a los 7 días fue del 26,8% La hazard ratio de mortalidad fue del 3,3; IC 95% 1,3-8,5 (la hazard ratio de mortalidad ajustada por edad fue de 2,1; IC 95% 0,8-5,8) si el tocilizumab se administraba después del inicio del distrés respiratorio.La administración precoz de tocilizumab en pacientes con suplementos de oxígeno podría ser crítica para la recuperación de los pacientes. Nuestros datos podrían ayudar a tomar decisiones clínicas hasta que se disponga de más información sobre el momento adecuado para iniciar el tratamiento con tocilizumab.

Significance: Hydropersulfides (RSSH) are ubiquitous in prokaryotes, eukaryotic cells, and mammalian tissues. The unique chemical properties and prevalent nature of these species suggest a crucial ...

Although SARS-CoV-2 vaccines immunogenicity in patients with cancer has been investigated, whether they can significantly improve the severity of COVID-19 in this specific population is undefined.Capitalizing on OnCovid (NCT04393974) registry data we reported COVID-19 mortality and proxies of COVID-19 morbidity, including post-COVID-19 outcomes, according to the vaccination status of the included patients.2090 eligible patients diagnosed with COVID-19 between 02/2020 and 11/2021 were included, of whom 1930 (92.3%) unvaccinated, 91 (4.4%) fully vaccinated and 69 (3.3%) partially vaccinated. With the exception of a higher prevalence of patients from the UK (p = 0.0003) and receiving systemic anticancer therapy at COVID-19 diagnosis (p = 0.0082) among fully vaccinated patients, no demographics/oncological features were associated with vaccination status. The 14-days case fatality rate (CFR) (5.5% vs 20.7%, p = 0.0004) and the 28-days CFR (13.2% vs 27.4%, p = 0.0028) demonstrated a significant improvement for fully vaccinated patients in comparison with unvaccinated patients. The receipt of prior full vaccination was also associated with reduced symptomatic COVID-19 (79.1% vs 88.5%, p = 0.0070), need of COVID-19 oriented therapy (34.9% vs 63.2%, p 0.0001), complications from COVID-19 (28.6% vs 39.4%, p = 0.0379), hospitalizations due to COVID-19 (42.2% vs 52.5%, p = 0.0007) and oxygen therapy requirement (35.7% vs 52%, p = 0.0036). Following Inverse Probability Treatment Weighting (IPTW) procedure no statistically significant difference according to the vaccination status was confirmed; however, all COVID-19 related outcomes were concordantly in favour of full vaccination. Among the 1228 (58.8%) patients who underwent a formal reassessment at participating centres after COVID-19 resolution, fully vaccinated patients experienced less sequelae than unvaccinated patients (6.7% vs 17.2%, p = 0.0320).This analysis provides initial evidence in support of the beneficial effect of SARS-CoV-2 vaccines against morbidity and mortality from COVID-19 in patients with cancer.

The omicron (B.1.1.529) variant of SARS-CoV-2 is highly transmissible and escapes vaccine-induced immunity. We aimed to describe outcomes due to COVID-19 during the omicron outbreak compared with the prevaccination period and alpha (B.1.1.7) and delta (B.1.617.2) waves in patients with cancer in Europe.In this retrospective analysis of the multicentre OnCovid Registry study, we recruited patients aged 18 years or older with laboratory-confirmed diagnosis of SARS-CoV-2, who had a history of solid or haematological malignancy that was either active or in remission. Patient were recruited from 37 oncology centres from UK, Italy, Spain, France, Belgium, and Germany. Participants were followed up from COVID-19 diagnosis until death or loss to follow-up, while being treated as per standard of care. For this analysis, we excluded data from centres that did not actively enter new data after March 1, 2021 (in France, Germany, and Belgium). We compared measures of COVID-19 morbidity, which were complications from COVID-19, hospitalisation due to COVID-19, and requirement of supplemental oxygen and COVID-19-specific therapies, and COVID-19 mortality across three time periods designated as the prevaccination (Feb 27 to Nov 30, 2020), alpha-delta (Dec 1, 2020, to Dec 14, 2021), and omicron (Dec 15, 2021, to Jan 31, 2022) phases. We assessed all-cause case-fatality rates at 14 days and 28 days after diagnosis of COVID-19 overall and in unvaccinated and fully vaccinated patients and in those who received a booster dose, after adjusting for country of origin, sex, age, comorbidities, tumour type, stage, and status, and receipt of systemic anti-cancer therapy. This study is registered with ClinicalTrials.gov, NCT04393974, and is ongoing.As of Feb 4, 2022 (database lock), the registry included 3820 patients who had been diagnosed with COVID-19 between Feb 27, 2020, and Jan 31, 2022. 3473 patients were eligible for inclusion (1640 [47·4%] were women and 1822 [52·6%] were men, with a median age of 68 years [IQR 57-77]). 2033 (58·5%) of 3473 were diagnosed during the prevaccination phase, 1075 (31·0%) during the alpha-delta phase, and 365 (10·5%) during the omicron phase. Among patients diagnosed during the omicron phase, 113 (33·3%) of 339 were fully vaccinated and 165 (48·7%) were boosted, whereas among those diagnosed during the alpha-delta phase, 152 (16·6%) of 915 were fully vaccinated and 21 (2·3%) were boosted. Compared with patients diagnosed during the prevaccination period, those who were diagnosed during the omicron phase had lower case-fatality rates at 14 days (adjusted odds ratio [OR] 0·32 [95% CI 0·19-0·61) and 28 days (0·34 [0·16-0·79]), complications due to COVID-19 (0·26 [0·17-0·46]), and hospitalisation due to COVID-19 (0·17 [0·09-0·32]), and had less requirements for COVID-19-specific therapy (0·22 [0·15-0·34]) and oxygen therapy (0·24 [0·14-0·43]) than did those diagnosed during the alpha-delta phase. Unvaccinated patients diagnosed during the omicron phase had similar crude case-fatality rates at 14 days (ten [25%] of 40 patients vs 114 [17%] of 656) and at 28 days (11 [27%] of 40 vs 184 [28%] of 656) and similar rates of hospitalisation due to COVID-19 (18 [43%] of 42 vs 266 [41%] of 652) and complications from COVID-19 (13 [31%] of 42 vs 237 [36%] of 659) as those diagnosed during the alpha-delta phase.Despite time-dependent improvements in outcomes reported in the omicron phase compared with the earlier phases of the pandemic, patients with cancer remain highly susceptible to SARS-CoV-2 if they are not vaccinated against SARS-CoV-2. Our findings support universal vaccination of patients with cancer as a protective measure against morbidity and mortality from COVID-19.National Institute for Health and Care Research Imperial Biomedical Research Centre and the Cancer Treatment and Research Trust.

Shaya Consortium ramped up its production from 60 KBOPD to almost 85 KBOPD as a result of an agile execution of its Field Development Plan, made of infill drilling, workover interventions, and full-field expansion of waterflooding. This combined activity made the planning process very complex and dynamic due to the high volume of operations and scenario evaluation. Additionally, the consortium was requested to provide a weekly production forecast to its major stakeholders highlighting all deviations from the original execution plan and remedial activities to come back on track. The proposed application tool has simplified and automated the forecasting processes using short-term updates of the executed activities from field reports, current well status, planned workover interventions, and new wells drilling schedule. Any deviation of the Annual Work Plan due to schedule variance or well performance is automatically adjusted by the tool, creating a new forecast to End-Of-Year or Quarter even Weekly, thus, reflecting the impact on the estimated recoverable volumes. The tool pulls information from different sources and consolidates them in a single unified environment, not only for forecasting but also as a visualization and analysis tool. Furthermore, it has several modules to facilitate the control of official type curves, scenario profiles for the Annual Work Plan, and it is fully linked to key corporate applications. This paper presents the development of a production forecasting tool that introduced a new way of working within the Shaya Production Team by improving activity scheduling and overcome underperforming new wells, keeping the operations team informed to facilitate the production management.

Cryptococcosis; Pulmonary malignancy Criptococcosi; Càncer de pulmó Criptococosis; Cáncer de pulmón

Growing evidence suggests that piriform cortex resection during anterior temporal lobectomy is important for achieving good seizure outcome in mesial temporal lobe epilepsy (mTLE). However, the relationship between seizure outcome and piriform cortex ablation during MR-guided laser interstitial thermal therapy (MRgLITT) remains unclear.To determine whether ablation of piriform cortex was associated with seizure outcome in patients with mTLE undergoing MRgLITT.We performed preablation and postablation volumetric analyses of hippocampus, amygdala, piriform cortex, and ablation volumes in patients with mTLE who underwent MRgLITT at our institution from 2014 to 2019.Thirty nine patients with mTLE were analyzed. In univariate logistic regression, percent piriform cortex ablation was associated with International League Against Epilepsy (ILAE) class 1 at 6 months (odds ratio [OR] 1.051, 95% CI [1.001-1.117], P = .045), whereas ablation volume, percent amygdala ablation, and percent hippocampus ablation were not ( P.05). At 1 year, ablation volume was associated with ILAE class 1 (OR 1.608, 95% CI [1.071-2.571], P = .021) while percent piriform cortex ablation became a trend (OR 1.050, 95% CI [0.994-1.109], P = .054), and both percent hippocampus ablation and percent amygdala ablation were not significantly associated with ILAE class 1 ( P.05). In multivariable logistic regression, only percent piriform cortex ablation was a significant predictor of seizure freedom at 6 months (OR 1.085, 95% CI [1.012-1.193], P = .019) and at 1 year (OR 1.074, 95% CI [1.003-1.178], P = .041).Piriform cortex ablation volume is associated with seizure outcome in patients with mTLE undergoing MRgLITT. The piriform cortex should be considered a high yield ablation target to achieve good seizure outcome.

Purpose We aim to assess risk factors related to early readmission in previous hospitalized patients with COVID-19. Methods We analyzed a retrospective cohort of patients with laboratory-confirmed COVID-19 admitted to Vall d’Hebron University Hospital, Barcelona, Spain. Early readmission was defined as the need for hospitalization within a period of 60 days after discharge. A descriptive analysis of the readmission was performed, including hospitalization outcome. We also performed a multivariate logistic regression to define risk factors for readmission Results A total of 629 patients were followed up during 60 days with a readmission cumulative incidence of 5.4% (34 out of 629) and an incidence rate of 0.034 person-years. Main reasons for readmission were respiratory worsening (13, 38.2%), decompensation of previous disease (12, 35.3%) or infectious complications (6, 17.6%). Median time to readmission was 12 days (interquartile range 7–33 days). Prior diagnosis of heart failure (OR 4.09; 95% CI 1.35–12.46; p = 0.013), length of stay during index admission greater than 13 days (OR 2.72; 95% CI 1.21–6.12; p = 0.015), treatment with corticosteroids (OR 2.39; 95% CI 1.01–5.70; p = 0.049) and developing pulmonary thromboembolism (OR 11.59; 95% CI 2.89–46.48; p = 0.001) were the risk factors statistically associated with early readmission. Conclusion Readmission cumulative incidence was 5.4%. Those patients with prior diagnosis of heart failure, length of stay greater than 13 days, treated with corticosteroids or who developed pulmonary thromboembolism might benefit from close monitoring after being discharged.

Introduction: Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are prevalent nosocomial infections with a worrisomely increasing prevalence of multidrug-resistant causative organisms, including those with resistance to carbapenems. The addition of relebactam, a β-lactamase inhibitor, to imipenem treatment restores the antimicrobial activity against the most of multidrug-resistant Gram-negative bacteria, including some carrying β‐lactamase enzyme-type carbapenemases. Areas covered: The aim of this article is to summarize the current evidence regarding imipenem/relebactam for the treatment of HAP/VAP. The authors discuss its chemistry, pharmacokinetics/pharmacodynamics, microbiology, tolerance and clinical efficacy. The results of clinical trials have demonstrated an efficacy of imipenem/relebactam similar to that of its comparator for the treatment of patients with HAP/VAP. Different studies have also shown its good safety profile, which is better than that of the combination of other β‐lactams with other antibiotics. Expert opinion: This drug should be incorporated as a new therapeutic option for the treatment of patients with HAP/VAP, especially as an alternative treatment in patients with confirmed infections caused by multidrug-resistant Gram-negatives.