Immune response against the SARS-CoV-2 spike protein in cancer patients after COVID-19 vaccination during the Omicron wave: a prospective study.

BACKGROUND: Cancer patients often have weakened immune systems, resulting in a lower response to vaccines, especially those receiving immunosuppressive oncological treatment (OT). We aimed to assess the impact of OT on the humoral and T-cell response to the B.1 lineage and Omicron variant following COVID-19 vaccination in patients with solid and hematological neoplasms. METHODS: We conducted a prospective study on cancer patients, stratified into OT and non-OT groups, who received a two-dose series of the COVID-19 mRNA vaccine and a booster six months later. The outcomes measured were the humoral (anti-SARS-CoV-2 S IgG titers and ACE2-S interaction inhibition capacity) and cellular (SARS-CoV-2 S-specific T-cell spots per million PBMCs) responses against the B.1 lineage and Omicron variant. These responses were evaluated four weeks after the second dose (n = 98) and eight weeks after the booster dose (n = 71). RESULTS: The humoral response after the second vaccine dose against the B.1 lineage and Omicron variant was significantly weaker in the OT group compared to the non-OT group (q-value<0.05). A booster dose of the mRNA-1273 vaccine significantly improved the humoral response in the OT group, making it comparable to the non-OT group. The mRNA-1273 vaccine, designed for the original Wuhan strain, elicited a weaker humoral response against the Omicron variant compared to the B.1 lineage, regardless of oncological treatment or vaccine dose. In contrast, T-cell responses against SARS-CoV-2, including the Omicron variant, were already present after the second vaccine dose and were not significantly affected by oncological treatments. CONCLUSIONS: Cancer patients, particularly those receiving immunosuppressive oncological treatments, should require booster doses and adapted COVID-19 vaccines for new SARS-CoV-2 variants like Omicron. Future studies should evaluate the durability of the immune response and the efficacy of individualized regimens.

[Thyroid surgery in a context of scarce resources at Saint Martin de Porres Dominican Hospital (Yaounde, Cameroon)]. / Chirurgie thyroïdienne dans le contexte de populations avec de faibles ressources à l'hôpital dominicain Saint Martin de Porres (Yaoundé, Cameroun).

Introduction: Surgical campaigns for thyroid surgery in low-income environments are very efficient, but there is little literature reporting results. These campaigns are complex due to multiple particularities: highly evolved cases, the need for professionals to travel or an obvious socio-cultural barrier influence towards the surgical act. We describe a surgical campaign in Cameroon to treat patients with goiter and issue some medical and sociocultural recommendations in view of our experience for its implementation with guarantees. Material and methods: An experienced group carried out an 11-day campaign at the Saint Martin de Porres Dominican Hospital, Yaounde, Cameroon. Demographic data, TSH values, surgery and complications after a 12-month follow-up were analyzed. Results: Thirty-eight patients with goiter were selected for the campaign and 32 patients (mean age, 40-years-old; 30 females) were operated. Bilateral goiter, as assessed with echography, was diagnosed in 13 patients (41%). Ten patients (31%) had a WHO grade II goiter (visible with the neck in a normal position). The surgical procedures were 18 unilateral thyroidectomy with isthmectomie, 13 total thyroidectomy, and 1 totalizing thyroidectomy, due to previous unilateral thyroidectomy (cancer recurrence). A pathological study in 13 patients (40%, extra cost 60 €) showed benign multinodular goiter/thyroid nodule (12 patients) and an extensive papillary carcinoma (one patient). Six months postoperatively, 3 patients had a slight dysphonia and one patient had persistent hypocalcemia. Follow-up was completed in all patients, either face to face (75%, 24 patients) or by phone (25%, 8 patients who failed to have a TSH test because of its cost, 23 €). Conclusions: Surgical campaigns to treat thyroid pathology can be carried out with guarantees if a series of important steps are followed: active participation of the patient's environment, thyroid ultrasound by the surgical team to decide which technique, intense awareness about monitoring and hormone replacement therapy, and the participation of local personnel for long-term follow-up.

Assessment and indicators of kinematic behavior and perceived fatigability

SUMMARY OBJECTIVE: The objective of this study was to investigate the relationship between upper limb kinetics and perceived fatigability in elderly individuals during an upper limb position sustained isometric task. METHODS: A total of 31 elderly participants, 16 men (72.94±4.49 years) and 15 women (72.27±6.05 years), performed a upper limb position sustained isometric task. Upper-limb acceleration was measured using an inertial measurement unit. Perceived fatigability was measured using the Borg CR10 scale. RESULTS: Higher mean acceleration in the x-axis throughout the activity was associated with higher final perceived fatigability scores. Moderate correlations were observed between perceived fatigability variation and mean acceleration cutoffs in all axes during the second half of the activity. In women, significant correlations were found between all perceived fatigability cutoffs and mean acceleration in the y- and x-axes. However, in men, the relationships between perceived fatigability variation and mean acceleration were more extensive and stronger. CONCLUSION: The acceleration pattern of the upper limb is linked to perceived fatigability scores and variation, with differences between sexes. Monitoring upper limb acceleration using a single inertial measurement unit can be a useful and straightforward method for identifying individuals who may be at risk of experiencing high perceived fatigability or task failure.

Effects of Myofascial Induction Therapy on Ankle Range of Motion and Pressure Pain Threshold in Trigger Points of the Gastrocnemius-A Clinical Trial.

BACKGROUND: The myofascial induction technique (MIT) has been shown to increase shoulder range of motion (ROM) in breast cancer survivors and decrease pain pressure threshold over the radial nerve in patients with epicondylalgia. To the authors' best knowledge, no study on trigger points and MIT has been published to date. The effect on ROM of latent trigger points is also unknown. METHODS: A total of 20 twins with one latent trigger point of the gastrocnemius muscle were evaluated pre- and post-MIT in the calf. We measured static footprint variables in a pre-post study. RESULTS: We found differences in PPT (p = 0.001) and no differences in ROM with knee flexed (p = 0.420) or stretched (p = 0.069). CONCLUSIONS: After Calf MIT, latent myofascial trigger points improve PPT but no change in ankle dorsiflexion with knee bent or knee flexed were found in non-restriction healthy subjects.

The Effectiveness of Hard Insoles for Plantar Pressure in Cycling: A Crossover Study.

BACKGROUND: Hard insoles have been proposed to decrease plantar pressure and prevent foot pain and paresthesia due to repetitive loading. The aim of this research was to analyze the effect of three different hard insoles in cycling on healthy subjects. METHODS: A crossover randomized trial was carried out. The mean age of the subjects was 35 ± 3.19 years, and all of them were men. While the subjects were cycling on a stationary bicycle, their plantar pressure was recorded with nine in-shoe sensors placed in nine specific foot areas to test a standard ethylene-vinyl-acetate 52° Shore A hardness insole, a polypropylene 58° Shore D insole, and a polypropylene 580 Shore D insole with selective aluminum 60 HB Brinell hardness in the metatarsal head and hallux. RESULTS: The maximum plantar pressure decreased significantly with the polypropylene insole containing selective aluminum in the metatarsal head and hallux areas. The maximum plantar data of the polypropylene aluminum insole in the M2 area (5.56 kgF/cm2), fifth metatarsal styloid process (6.48 kgF/cm2), M3-M4 area (4.97 kgF/cm2), and hallux (8.91 kgF/cm2) were of particular interest compared to the other insoles. CONCLUSIONS: The use of insoles made of polypropylene with aluminum in the metatarsal head and hallux areas decreases the maximum plantar pressure in cycling compared to standard EVA and polypropylene insoles.

Epidemiological and Clinical Characteristics of Patients Admitted to a Secondary Hospital with Suspected MPOX Virus Infection: Is HIV Playing a Role?

MPOX (monkeypox) is a zoonotic viral disease, endemic in some Central and West African countries. However, in May 2022, cases began to be reported in non-endemic countries, demonstrating community transmission. Since the beginning of the outbreak, different epidemiological and clinical behaviors have been observed. We conducted an observational study at a secondary hospital in Madrid to characterize suspected and confirmed cases of MPOX epidemiologically and clinically. Besides the general descriptive analysis, we compared data between HIV-positive and HIV-negative subjects; 133 patients were evaluated with suspected MPOX, of which 100 were confirmed. Regarding positive cases, 71.0% were HIV positive, and 99.0% were men with a mean age of 33. In the previous year, 97.6% reported having sex with men, 53.6% used apps for sexual encounters, 22.9% practiced chemsex, and 16.7% went to saunas. Inguinal adenopathies were significantly higher in MPOX cases (54.0% vs. 12.1%, p < 0.001), as the involvement of genital and perianal area (57.0% vs. 27.3% and 17.0% vs. 1.0%, p = 0.006 and p = 0.082 respectively). Pustules were the most common skin lesion (45.0%). In HIV-positive cases, only 6.9% had a detectable viral load, and the mean CD4 count was 607.0/mm3. No significant differences were observed in the disease course, except for a greater tendency towards the appearance of perianal lesions. In conclusion, the MPOX 2022 outbreak in our area has been related to sexual intercourse among MSM, with no severe clinical cases nor apparent differences in HIV and non-HIV patients.

Pseudomonas aeruginosa Community-Onset Bloodstream Infections: Characterization, Diagnostic Predictors, and Predictive Score Development-Results from the PRO-BAC Cohort.

Community-onset bloodstream infections (CO-BSI) caused by gram-negative bacilli are common and associated with significant mortality; those caused by Pseudomonas aeruginosa are associated with worse prognosis and higher rates of inadequateempirical antibiotic treatment. The aims of this study were to describe the characteristics of patients with CO-BSI caused by P. aeruginosa, to identify predictors, and to develop a predictive score for P. aeruginosa CO-BSI. Materials/methods: PROBAC is a prospective cohort including patients >14 years with BSI from 26 Spanish hospitals between October 2016 and May 2017. Patients with monomicrobial P. aeruginosa CO-BSI and monomicrobial Enterobacterales CO-BSI were included. Variables of interest were collected. Independent predictors of Pseudomonas aeruginosa CO-BSI were identified by logistic regression and a prediction score was developed. Results: A total of 78patients with P. aeruginosa CO-BSI and 2572 with Enterobacterales CO-BSI were included. Patients with P. aeruginosa had a median age of 70 years (IQR 60−79), 68.8% were male, median Charlson score was 5 (IQR 3−7), and 30-daymortality was 18.5%. Multivariate analysis identified the following predictors of CO-BSI-PA [adjusted OR (95% CI)]: male gender [1.89 (1.14−3.12)], haematological malignancy [2.45 (1.20−4.99)], obstructive uropathy [2.86 (1.13−3.02)], source of infection other than urinary tract, biliary tract or intra-abdominal [6.69 (4.10−10.92)] and healthcare-associated BSI [1.85 (1.13−3.02)]. Anindex predictive of CO-BSI-PA was developed; scores ≥ 3.5 showed a negative predictive value of 89% and an area under the receiver operator curve (ROC) of 0.66. Conclusions: We did not find a good predictive score of P. aeruginosa CO-BSI due to its relatively low incidence in the overall population. Our model includes variables that are easy to collect in real clinical practice and could be useful to detect patients with very low risk of P. aeruginosa CO-BSI.

Risk Factors and Predictive Score for Bacteremic Biliary Tract Infections Due to Enterococcus faecalis and Enterococcus faecium: a Multicenter Cohort Study from the PROBAC Project.

Biliary-tract bloodstream infections (BT-BSI) caused by Enterococcus faecalis and E. faecium are associated with inappropriate empirical treatment and worse outcomes compared to other etiologies. The objective of this study was to investigate the risk factors for enterococcal BT-BSI. Patients with BT-BSI from the PROBAC cohort, including consecutive patients with BSI in 26 Spanish hospitals between October 2016 and March 2017, were selected; episodes caused by E. faecalis or E. faecium and other causes were compared. Independent predictors for enterococci were identified by logistic regression, and a predictive score was developed. Eight hundred fifty episodes of BT-BSI were included; 73 (8.5%) were due to target Enterococcus spp. (48 [66%] were E. faecium and 25 [34%] E. faecalis). By multivariate analysis, the variables independently associated with Enterococcus spp. were (OR; 95% confidence interval): cholangiocarcinoma (4.48;1.32 to 15.25), hospital acquisition (3.58;2.11 to 6.07), use of carbapenems in the previous month (3.35;1.45 to 7.78), biliary prosthesis (2.19;1.24 to 3.90), and moderate or severe chronic kidney disease (1.55;1.07 to 2.26). The AUC of the model was 0.74 [95% CI0.67 to 0.80]. A score was developed, with 7, 6, 5, 4, and 2 points for these variables, respectively, with a negative predictive value of 95% for a score ≤ 6. A model, including cholangiocarcinoma, biliary prosthesis, hospital acquisition, previous carbapenems, and chronic kidney disease showed moderate prediction ability for enterococcal BT-BSI. Although the score will need to be validated, this information may be useful for deciding empirical therapy in biliary tract infections when bacteremia is suspected. IMPORTANCE Biliary tract infections are frequent, and a significant cause of morbidity and mortality. Bacteremia is common in these infections, particularly in the elderly and patients with cancer. Inappropriate empirical treatment has been associated with increased risk of mortality in bacteremic cholangitis, and the probability of receiving inactive empirical treatment is higher in episodes caused by enterococci. This is because many of the antimicrobial agents recommended in guidelines for biliary tract infections lack activity against these organisms. To the best of our knowledge, this is the first study analyzing the predictive factors for enterococcal BT-BSI and deriving a predictive score.

A 120-second stretch improves postural control and plantar pressure: quasi-experimental study

ABSTRACT BACKGROUND: There are no studies on long-term bilateral calf stretching in relation to balance and plantar pressure. OBJECTIVES: To demonstrate that there is better control of posture and pressures after continuous stretching of the posterior calf muscles. DESIGN AND SETTING: Pre and post-intervention study conducted in a private clinic. METHODS: We measured static footprints and stabilometry before and after continuous passive plantar flexor stretching of duration 120 seconds, among 24 healthy subjects. RESULTS: We found differences in Y displacement with eyes closed (P = 0.010), but not among other variables with eyes closed: X displacement (P = 0.263); surface (P = 0.940); laterolateral speed displacement (P = 0.279); and anteroposterior speed displacement (P = 0.914). There were also no differences in eyes-open variables: X displacement (P = 0.341); Y displacement (P = 0.491); surface (P = 0.167); laterolateral speed displacement (P = 0.852); and anteroposterior speed displacement (P = 0.079). The plantar pressures in the heel (maximum pressure, P = 0.048; mean pressure, P = 0.001) and in the midfoot (maximum pressure, P = 0.004; mean pressure, P = 0.004) were reduced, but not in the forefoot (maximum pressure, P = 0.391; mean pressure, P = 0.225). The surface became larger in the forefoot (P = 0.000) and midfoot (P = 0.021). CONCLUSIONS: Continuous static stretching of plantar flexors for 120 seconds improved stance balance and reduced plantar pressures (maximum and mean) in the rearfoot and midfoot. It also increased the surface in the midfoot and forefoot. TRIAL REGISTRATION: at clinicaltrials.gov, under the number NTC03743168.

High BMP4 expression in low/intermediate risk BCP-ALL identifies children with poor outcomes.

Pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) outcome has improved in the last decades, but leukemic relapses are still one of the main problems of this disease. Bone morphogenetic protein 4 (BMP4) was investigated as a new candidate biomarker with potential prognostic relevance, and its pathogenic role was assessed in the development of disease. A retrospective study was performed with 115 pediatric patients with BCP-ALL, and BMP4 expression was analyzed by quantitative reverse transcription polymerase chain reaction in leukemic blasts at the time of diagnosis. BMP4 mRNA expression levels in the third (upper) quartile were associated with a higher cumulative incidence of relapse as well as a worse 5-year event-free survival and central nervous system (CNS) involvement. Importantly, this association was also evident among children classified as having a nonhigh risk of relapse. A validation cohort of 236 patients with BCP-ALL supported these data. Furthermore, high BMP4 expression promoted engraftment and rapid disease progression in an NSG mouse xenograft model with CNS involvement. Pharmacological blockade of the canonical BMP signaling pathway significantly decreased CNS infiltration and consistently resulted in amelioration of clinical parameters, including neurological score. Mechanistically, BMP4 favored chemoresistance, enhanced adhesion and migration through brain vascular endothelial cells, and promoted a proinflammatory microenvironment and CNS angiogenesis. These data provide evidence that BMP4 expression levels in leukemic cells could be a useful biomarker to identify children with poor outcomes in the low-/intermediate-risk groups of BCP-ALL and that BMP4 could be a new therapeutic target to blockade leukemic CNS disease.

Age-Adjusted Endothelial Activation and Stress Index for Coronavirus Disease 2019 at Admission Is a Reliable Predictor for 28-Day Mortality in Hospitalized Patients With Coronavirus Disease 2019.

Background: Endothelial Activation and Stress Index (EASIX) predict death in patients undergoing allogeneic hematopoietic stem cell transplantation who develop endothelial complications. Because coronavirus disease 2019 (COVID-19) patients also have coagulopathy and endotheliitis, we aimed to assess whether EASIX predicts death within 28 days in hospitalized COVID-19 patients. Methods: We performed a retrospective study on COVID-19 patients from two different cohorts [derivation (n = 1,200 patients) and validation (n = 1,830 patients)]. The endpoint was death within 28 days. The main factors were EASIX [(lactate dehydrogenase * creatinine)/thrombocytes] and aEASIX-COVID (EASIX * age), which were log2-transformed for analysis. Results: Log2-EASIX and log2-aEASIX-COVID were independently associated with an increased risk of death in both cohorts (p < 0.001). Log2-aEASIX-COVID showed a good predictive performance for 28-day mortality both in the derivation cohort (area under the receiver-operating characteristic = 0.827) and in the validation cohort (area under the receiver-operating characteristic = 0.820), with better predictive performance than log2-EASIX (p < 0.001). For log2 aEASIX-COVID, patients with low/moderate risk (<6) had a 28-day mortality probability of 5.3% [95% confidence interval (95% CI) = 4-6.5%], high (6-7) of 17.2% (95% CI = 14.7-19.6%), and very high (>7) of 47.6% (95% CI = 44.2-50.9%). The cutoff of log2 aEASIX-COVID = 6 showed a positive predictive value of 31.7% and negative predictive value of 94.7%, and log2 aEASIX-COVID = 7 showed a positive predictive value of 47.6% and negative predictive value of 89.8%. Conclusion: Both EASIX and aEASIX-COVID were associated with death within 28 days in hospitalized COVID-19 patients. However, aEASIX-COVID had significantly better predictive performance than EASIX, particularly for discarding death. Thus, aEASIX-COVID could be a reliable predictor of death that could help to manage COVID-19 patients.

Current advances and novel research on minimal invasive techniques for musculoskeletal disorders.

The present review summarized the current advances and novel research on minimal invasive techniques for musculoskeletal disorders. Different invasive approaches were proposed in the physical therapy field for the management of musculoskeletal disorders, such as ultrasound-guided percutaneous needle electrolysis, dry needling, acupuncture and other invasive therapy techniques, discussing about their worldwide status, safety and interventional ultrasound imaging. Indeed, dry needling may be one of the most useful and studies invasive physical therapy applications in musculoskeletal disorders of different body regions, such as back, upper limb, shoulder, arm, hand, pelvis, lower limb, neck, head, or temporomandibular joint, and multiple soreness location disorders, such as fibromyalgia. In addition, the assessment and treatment by acupuncture or electro-acupuncture was considered and detailed for different conditions such as plantar fasciitis, osteoarthritis, spasticity, myofascial pain syndrome, osteoporosis and rheumatoid arthritis. As an increasing technique in physical therapy, the use of ultrasound-guided percutaneous needle electrolysis was discussed in injuries of the musculoskeletal system and entrapment neuropathies. Also, ultrasound-guided percutaneous neuromodulation was established as a rising technique combined with ultrasound evaluation of the peripheral nerve system with different clinical applications which need further studies to detail their effectiveness in different musculoskeletal conditions. Thus, invasive physical therapy may be considered as a promising approach with different novel applications in several musculoskeletal disorders and a rising use in the physiotherapy field.

Intra and intersession repeatability and reliability of dynamic parameters in pressure platform assessments on subjects with simulated leg length discrepancy. A cross-sectional research

ABSTRACT BACKGROUND: Leg length discrepancy (LLD) may play a key role in exercise biomechanics. Although the Podoprint platform has been used in dynamic pressure studies, there are no data regarding the reliability and repeatability of dynamic measurements under simulated LLD conditions. OBJECTIVES: To determine the intra and intersession repeatability and reliability of dynamic parameters of the Podoprint pressure platform under simulated LLD conditions. DESIGN AND SETTING: Observational cross-sectional study at a public university. METHODS: Thirty-seven healthy volunteers participated in this study. LLD was simulated using ethyl vinyl acetate plantar lifts with heights of 5 mm, 10 mm, 15 mm and 20 mm located under the right shoe of each volunteer. The procedure was performed to capture the dynamic parameters of each participant under five different simulated LLD conditions. Stance time, mean pressure and peak pressure measurements were registered in three trials for each foot and each LLD level. Data were collected during two separate testing sessions, in order to establish intrasession and intersession reliability. RESULTS: The intraclass correlation coefficients (ICCs) for intrasession reliability ranged from 0.775 to 0.983 in the first session and from 0.860 to 0.985 in the second session. The ICCs for intersession reliability ranged from 0.909 to 0.990. Bland-Altman plots showed absence of systematic measurement errors. CONCLUSIONS: The results from this study indicate that the Podoprint platform is a reliable system for assessing dynamic parameters under simulated LLD conditions. Future studies should evaluate plantar pressures under LLD conditions, in association with exercise, biomechanics and musculoskeletal disorders.

Impact of lifestyle on health-related quality of life among young university students: a cross-sectional study

ABSTRACT BACKGROUND: Lifestyle is strongly involved in the pathogenesis and progression of non-communicable diseases, and has a great impact on quality of life. The goal of the present study was to analyze the lifestyle and body composition (BC) of young university students during the pandemic, and their relationship with health-related quality of life (HrQoL). DESIGN AND SETTING: Observational cross-sectional study conducted in the Universidad Europea de Madrid, Spain. METHODS: A total sample of 56 healthy university students was recruited. Activity, sitting time, adherence to Mediterranean diet and BC were measured. RESULTS: Regarding BC, only 5% and 10.7% of the subjects had health risk values for waist circumference and waist-to-height ratio, respectively. The mean daily sitting-time was 8.26 hours, while 19.64% of the subjects spent . 10 hours per day sitting. 92.86% of the subjects complied with the World Health Organization 2020 physical activity recommendations. The mean PREDIMED score was 7.41, while 51.8% of the subjects had low adherence to the Mediterranean diet. Regarding HrQoL, 22 subjects (39.2%) and 26 subjects (46.4%) were in the lowest quintile of physical component summary and mental component summary, respectively, according to the reference values for their age range. There was a negative correlation between physical function and sitting time (r = -0.38). CONCLUSIONS: There were high levels of sedentary behavior and low HrQoL values, with a negative moderate correlation between these variables. The findings from the present study especially highlight the importance of implementing public health programs targeting reduction of sitting time among university students.

Involvement of Mesenchymal Stem Cells in Oral Mucosal Bacterial Immunotherapy.

Recent clinical observations indicate that bacterial vaccines induce cross-protection against infections produced by different microorganisms. MV130, a polyvalent bacterial sublingual preparation designed to prevent recurrent respiratory infectious diseases, reduces the infection rate in patients with recurrent respiratory tract infections. On the other hand, mesenchymal stem cells (MSCs) are key cell components that contribute to the maintenance of tissue homeostasis and exert both immunostimulatory and immunosuppressive functions. Herein, we study the effects of MV130 in human MSC functionality as a potential mechanism that contributes to its clinical benefits. We provide evidence that during MV130 sublingual immunization of mice, resident oral mucosa MSCs can take up MV130 components and their numbers remain unchanged after vaccination, in contrast to granulocytes that are recruited from extramucosal tissues. MSCs treated in vitro with MV130 show an increased viability without affecting their differentiation potential. In the short-term, MSC treatment with MV130 induces higher leukocyte recruitment and T cell expansion. In contrast, once T-cell activation is initiated, MV130 stimulation induces an up-regulated expression of immunosuppressor factors in MSCs. Accordingly, MV130-primed MSCs reduce T lymphocyte proliferation, induce the differentiation of dendritic cells with immunosuppressive features and favor M2-like macrophage polarization, thus counterbalancing the immune response. In addition, MSCs trained with MV130 undergo functional changes, enhancing their immunomodulatory response to a secondary stimulus. Finally, we show that MSCs are able to uptake, process and retain a reservoir of the TLR ligands derived from MV130 digestion which can be subsequently transferred to dendritic cells, an additional feature that also may be associated to trained immunity.

Characteristics, complications and outcomes among 1549 patients hospitalised with COVID-19 in a secondary hospital in Madrid, Spain: a retrospective case series study.

OBJECTIVES: To describe demographic, clinical, radiological and laboratory characteristics, as well as outcomes, of patients admitted for COVID-19 in a secondary hospital. DESIGN AND SETTING: Retrospective case series of sequentially hospitalised patients with confirmed SARS-CoV-2, at Infanta Leonor University Hospital (ILUH) in Madrid, Spain. PARTICIPANTS: All patients attended at ILUH testing positive to reverse transcriptase-PCR on nasopharyngeal swabs and diagnosed with COVID-19 between 1 March 2020 and 28 May 2020. RESULTS: A total of 1549 COVID-19 cases were included (median age 69 years (IQR 55.0-81.0), 57.5% men). 78.2% had at least one underlying comorbidity, the most frequent was hypertension (55.8%). Most frequent symptoms at presentation were fever (75.3%), cough (65.7%) and dyspnoea (58.1%). 81 (5.8%) patients were admitted to the intensive care unit (ICU) (median age 62 years (IQR 51-71); 74.1% men; median length of stay 9 days (IQR 5-19)) 82.7% of them needed invasive ventilation support. 1393 patients had an outcome at the end of the study period (case fatality ratio: 21.2% (296/1393)). The independent factors associated with fatality (OR; 95% CI): age (1.07; 1.06 to 1.09), male sex (2.86; 1.85 to 4.50), neurological disease (1.93; 1.19 to 3.13), chronic kidney disease (2.83; 1.40 to 5.71) and neoplasia (4.29; 2.40 to 7.67). The percentage of hospital beds occupied with COVID-19 almost doubled (702/361), with the number of patients in ICU quadrupling its capacity (32/8). Median length of stay was 9 days (IQR 6-14). CONCLUSIONS: This study provides clinical characteristics, complications and outcomes of patients with COVID-19 admitted to a European secondary hospital. Fatal outcomes were similar to those reported by hospitals with a higher level of complexity.

The PANDEMYC Score. An Easily Applicable and Interpretable Model for Predicting Mortality Associated With COVID-19.

This study aimed to build an easily applicable prognostic model based on routine clinical, radiological, and laboratory data available at admission, to predict mortality in coronavirus 19 disease (COVID-19) hospitalized patients. METHODS: We retrospectively collected clinical information from 1968 patients admitted to a hospital. We built a predictive score based on a logistic regression model in which explicative variables were discretized using classification trees that facilitated the identification of the optimal sections in order to predict inpatient mortality in patients admitted with COVID-19. These sections were translated into a score indicating the probability of a patient's death, thus making the results easy to interpret. RESULTS: Median age was 67 years, 1104 patients (56.4%) were male, and 325 (16.5%) died during hospitalization. Our final model identified nine key features: age, oxygen saturation, smoking, serum creatinine, lymphocytes, hemoglobin, platelets, C-reactive protein, and sodium at admission. The discrimination of the model was excellent in the training, validation, and test samples (AUC: 0.865, 0.808, and 0.883, respectively). We constructed a prognostic scale to determine the probability of death associated with each score. CONCLUSIONS: We designed an easily applicable predictive model for early identification of patients at high risk of death due to COVID-19 during hospitalization.

The choroid plexus stroma constitutes a sanctuary for paediatric B-cell precursor acute lymphoblastic leukaemia in the central nervous system.

Despite current central nervous system-directed therapies for childhood B-cell precursor acute lymphoblastic leukaemia, relapse at this anatomical site still remains a challenging issue. Few reports have addressed the study of the specific cellular microenvironments which can promote the survival, quiescence, and therefore chemoresistance of B-cell precursor acute lymphoblastic leukaemia cells in the central nervous system. Herein, we showed by immunofluorescence and electron microscopy that in xenotransplanted mice, leukaemic cells infiltrate the connective tissue stroma of the choroid plexus, the brain structure responsible for the production of cerebrospinal fluid. The ultrastructural study also showed that leukaemia cells are able to migrate through blood vessels located in the choroid plexus stroma. In short-term co-cultures, leukaemic cells established strong interactions with human choroid plexus fibroblasts, mediated by an increased expression of ITGA4 (VLA-4)/ITGAL (LFA-1) and their ligands VCAM1/ICAM1. Upon contact with leukaemia cells, human choroid plexus fibroblasts acquired a cancer-associated fibroblast phenotype, with an increased expression of α-SMA and vimentin as well as pro-inflammatory factors. Human choroid plexus fibroblasts also have the capacity to reduce the proliferative index of leukaemic blasts and promote their survival and chemoresistance to methotrexate and cytarabine. The inhibition of VLA-4/VCAM-1 interactions using anti-VLA-4 antibodies, and the blockade of Notch signalling pathway by using a γ-secretase inhibitor partially restored chemotherapy sensitivity of leukaemia cells. We propose that the choroid plexus stroma constitutes a sanctuary for B-cell precursor acute lymphoblastic leukaemia cells in the central nervous system. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

Influence of Different Hardness Custom Foot Insoles in the Electromyography Activity Patterns of the Thigh and Hip Muscles during Motorcycling Sport: A Crossover Study.

: Nowadays, the use of insoles in sport practice have been recognized to decrease the foot and lower limb injury patterns. The aim of this study was to analyse the effect of four types of hardness insoles (HI) in the activity patterns of the hip and thigh muscles (HTM) in motoriders during motorcycling sport. The study was a crossover trial. Subjects were elite motoriders. The mean age was 33 ± 5.14 years. Electromyography (EMG) of hip and thigh muscles (HTM) data was registered via surface while subjects were riding on an elite motorcycle simulator. Subjects had to complete different tests with randomly hardest insoles (HI): 1: only polypropylene (58° D Shore); 2: Polypropylene (58° D Shore) with selective aluminium in hallux and metatarsal heads (60 HB Brinell hardness); 3: Ethylene vinyl acetate (EVA) (52° A Shore); and finally, 4: Ordinary EVA (25° A Shore) as the control. EMG patterns of the HTM, riding on an elite motorcycle simulator, showed the lowest peak amplitude with the insoles with polypropylene and selective aluminium. Using the hardest insoles in our study (selective aluminium) the EMG amplitude peaks decreased in all HTM.

Acute Lymphoblastic Leukaemia Cells Impair Dendritic Cell and Macrophage Differentiation: Role of BMP4.

Dendritic cells and macrophages are common components of the tumour immune microenvironment and can contribute to immune suppression in both solid and haematological cancers. The Bone Morphogenetic Protein (BMP) pathway has been reported to be involved in cancer, and more recently in leukaemia development and progression. In the present study, we analyse whether acute lymphoblastic leukaemia (ALL) cells can affect the differentiation of dendritic cells and macrophages and the involvement of BMP pathway in the process. We show that ALL cells produce BMP4 and that conditioned media from ALL cells promote the generation of dendritic cells with immunosuppressive features and skew M1-like macrophage polarization towards a less pro-inflammatory phenotype. Likewise, BMP4 overexpression in ALL cells potentiates their ability to induce immunosuppressive dendritic cells and favours the generation of M2-like macrophages with pro-tumoral features. These results suggest that BMP4 is in part responsible for the alterations in dendritic cell and macrophage differentiation produced by ALL cells.