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Chronic pancreatitis is associated with impaired quality of life, high incidence of comorbidities, serious complications and mortality. Healthcare costs are exorbitant. Some medical societies have developed guidelines for treatment based on scientific evidence, but the gathered level of evidence for any individual topic is usually low and, therefore, recommendations tend to be vague or weak. In the present position papers on chronic pancreatitis from the Societat Catalana de Digestologia and the Societat Catalana de Pàncrees we aimed at providing defined position statements for the clinician based on updated review of published literature and on multidisciplinary expert agreement. The final goal is to propose the use of common terminology and rational diagnostic/therapeutic circuits based on current knowledge. To this end 51 sections related to chronic pancreatitis were reviewed by 21 specialists from 6 different fields to generate 88 statements altogether. Statements were designed to harmonize concepts or delineate recommendations. Part 2 of these paper series discuss topics on treatment and follow-up. The therapeutic approach should include assessment of etiological factors, clinical manifestations and complications. The complexity of these patients advocates for detailed evaluation in multidisciplinary committees where conservative, endoscopic, interventional radiology or surgical options are weighed. Specialized multidisciplinary units of Pancreatology should be constituted. Indications for surgery are refractory pain, local complications, and suspicion of malignancy. Enzyme replacement therapy is indicated if evidence of exocrine insufficiency or after pancreatic surgery. Response should be evaluated by nutritional parameters and assessment of symptoms. A follow-up program should be planned for every patient with chronic pancreatitis. © 2021 Elsevier España, S.L.U.

The Hannover classification of vestibular schwannomas is designed to stratify tumors based on extrameatal extension and compression of the brainstem. We have previously reported the reliability of the Koos system, but to date, no study has assessed the reliability of the similar Hannover classification.We present an assessment of the intrarater and interrater reliability of the Hannover classification system.After institutional review board approval was obtained, a cross-sectional group of the magnetic resonance imaging of 40 patients with vestibular schwannomas varying in size comprised the study sample. Four raters were selected to assign a Hannover grade to 50 total scans. Interrater and intrarater reliability was calculated and reported using Fleiss's kappa, Kendall's W, and intraclass correlation coefficient (ICC).Interrater observer reliability was found to be moderate when measured using Fleiss' kappa (0.49), extremely strong using Kendall's W (0.93), and excellent as calculated by ICC (0.88). The results were all statistically significant (P0.05). Intrarater reliability for Hannover grade ranged from 0.77 to 1.00 (substantial to perfect). By Kendall's W and ICC, all raters had near perfect or excellent agreement. The results were all statistically significant (P0.05).The Hannover classification is a reliable system for grading the size of vestibular schwannomas. This supports its continued use and previously published results of the literature in studies relying on this classification. Further studies are needed to evaluate its validity and determine its role in preoperative counseling and determining microsurgery and radiosurgery outcomes.

Background and ObjectivesTo report the clinical, biological, and imaging features and clinical course of a French cohort of patients with glial fibrillary acidic protein (GFAP) autoantibodies.MethodsWe retrospectively included all patients who tested positive for GFAP antibodies in the CSF by immunohistochemistry and confirmed by cell-based assay using cells expressing human GFAPα since 2017 from 2 French referral centers.ResultsWe identified 46 patients with GFAP antibodies. Median age at onset was 43 years, and 65% were men. Infectious prodromal symptoms were found in 82%. Other autoimmune diseases were found in 22% of patients, and coexisting neural autoantibodies in 11%. Tumors were present in 24%, and T-cell dysfunction in 23%. The most frequent presentation was subacute meningoencephalitis (85%), with cerebellar dysfunction in 57% of cases. Other clinical presentations included myelitis (30%) and visual (35%) and peripheral nervous system involvement (24%). MRI showed perivascular radial enhancement in 32%, periventricular T2 hyperintensity in 41%, brainstem involvement in 31%, leptomeningeal enhancement in 26%, and reversible splenial lesions in 4 cases. A total of 33 of 40 patients had a monophasic course, associated with a good outcome at last follow-up (Rankin Score ≤2: 89%), despite a severe clinical presentation. Adult and pediatric features are similar. Thirty-two patients were treated with immunotherapy. A total of 11/22 patients showed negative conversion of GFAP antibodies.DiscussionGFAP autoimmunity is mainly associated with acute/subacute meningoencephalomyelitis with prodromal symptoms, for which tumors and T-cell dysfunction are frequent triggers. The majority of patients followed a monophasic course with a good outcome.

Sickle cell anemia (SCA) is a genetic disorder characterized by chronic hemolysis and the presence of erythrocytes with low deformability, which may trigger vaso-occlusive crises. We tested the in-vitro effects of aqueous extract of chives (Allium schoenoprasum L.) on erythrocyte deformability of SCA patients. Blood samples from 6 apparently healthy volunteers and 5 SCA patients were collected into heparin coated tubes. Both apparently healthy and SCA patient blood samples were incubated with 80μg/mL chives plant aqueous extract at 37°C for 60 min and erythrocyte deformability was measured by ektacytometry (3 Pa and 30 Pa; 37°C). Results of incubation of apparently healthy blood samples with plant extract showed that incubation did not alter erythrocyte deformability significantly. However, for SCA blood samples, erythrocyte deformability decreased significantly with plant extract exposure at 3 Pa (p

Autoimmune haemolytic anaemia (AIHA) is a rare immune-related adverse event and appears to be more common with anti-PD1/PDL1 than anti-CTLA4. Little is known about the safety of re-treating with anti-PD1/PDL1 or changing to anti-CTLA4. We present a case of grade 4 AIHA due to nivolumab (PD1-inhibitor) treatment in a patient with melanoma for adjuvant setting after surgery and the safeness of subsequent treatment with ipilimumab (anti-CTLA4). After the remission of AIHA with steroids, ipilimumab was started with the rationale of its different mechanism of action. Fortunately, AIHA did not recur. The mechanism by which checkpoint inhibitors cause AIHA is likely by augmenting or redirecting immune surveillance, especially by activating pre-existing red blood cell autoantibodies, but further studies must be done. To our knowledge, this is the first case published in the literature with the change of immunotherapy treatment to anti-CTLA4.

The monoamine hypothesis of depression attributes the symptoms of major depressive disorders to imbalances of serotonin, noradrenaline, and dopamine in the limbic areas of the brain. The preferential targeting of serotonin receptor (SERT) by selective serotonin reuptake inhibitors (SSRIs) has offered an opportunity to reduce the range of these side effects and improve patient adherence to pharmacotherapy. Clozapine remains an effective drug against treatment-resistant schizophrenia, defined as failing treatment with at least two different antipsychotic medications. Patients with schizophrenia who display a constellation of negative symptoms respond poorly to antipsychotic monotherapy. Negative symptoms include the diminution of motivation, interest, or expression. Conversely to the depressive symptomology of interest presently, supplementation of antipsychotics with SSRIs in schizophrenic patients with negative symptoms lead to synergistic improvements in the function of these patients. Fluvoxamine is one of the most potent inhibitors of CYP1A2 and can lead to an increase in clozapine levels. Similar increases in serum clozapine were detected in two patients taking sertraline. However, studies have been contradictory as well, showing no such increases, which are worrying. Clinicians should be aware that clozapine levels should be monitored with any coadministration with SSRIs.

The main objective of the present study was to provide seasonal variation data for inter-limb asymmetry in youth elite team-sport athletes. Fifty-nine players performed the single leg countermovement jump (SLCMJ) and the one leg hop for distance (OLHT) tests during pre-season, mid-season and end-season. A repeated-measures analysis of variance was conducted to determine magnitude differences in asymmetry scores between time points. Kappa coefficients (κ) were calculated to determine the levels of agreement for the direction of asymmetry. When comparing inter-limb asymmetry magnitudes across the season, the SLCMJ test showed significantly higher asymmetries at mid-season in comparison with pre-season and end-season (p

Background The role of statins in the management of dyslipidemia in elderly patients with different cardiovascular risks remains unclear. Objective To study use of statins and associated factors in subjects aged 90 or over in the Community of Madrid, Spain. Methods Observational, cross-sectional study that included all people aged 90 or more residing in the Community of Madrid as of December 31, 2015. The clinical information was obtained from the database that contains the electronic medical records collected by family doctors in primary care. Comorbidity data are collected according to the International Classification of Primary Care, Second Edition (ICPC-2). Results The study population comprised 59,423 subjects, with a mean age of 93.3 (2.5) years (25.8% males). Slightly more than one quarter of the population (28.2%) was in treatment with statins, 21.9% were in primary prevention, and 48.1% in secondary prevention. The multivariate analysis revealed the factors independently associated with statin treatment to be younger age, not being institutionalized, a higher Barthel score, a lower Charlson score, a higher body mass index, and a history of diabetes, dyslipidemia, chronic kidney disease, and cardiovascular disease. Conclusions A significant percentage of nonagenarians—mainly less frail patients with more comorbidities—in the Community of Madrid receive statin treatment. No clear efficacy has been demonstrated in reducing cardiovascular events in an age group with such a short life expectancy.

Purpose: To describe the clinical and epidemiological characteristics of patients with Vogt-Koyanagi-Harada (VKH) disease in Spain. Methods: This was a retrospective multicenter analysis of data from VKH patients followed for at least 6 months. The data collected were related to demographics, clinical manifestations, treatments, and complications. Results: Participants were 112 patients (224 eyes), from 13 tertiary referral centers, of mean age 37.5 ± 14.7 years; 83.9% were women. Ethnicities were 61.6% Caucasian and 30.4% Hispanic. The disease was classified as complete in 16.1%, incomplete in 55.4%, and probable in 28.6%. When seen for the first time, the clinical course was acute in 69.6%, recurrent chronic in 15.2%, and chronic in 14.3%. The most frequent treatment was corticosteroids (acute stage 42.2%, maintenance stage 55.6%). The most common complications were cataract (41.1%) and ocular hypertension (16.1%). In most eyes, visual acuity was improved (96.7%) or remained stable at the end of follow up. Conclusion: VKH in Spain mostly affects women and presents as incomplete acute stage disease. Visual prognosis is good. Cataract and glaucoma are the two most frequent complications.

Heart failure is twice as common in men with type 2 diabetes than those without it and is almost five times greater in women with diabetes. Ideally, effective treatment for one condition also will help with the other; certainly, clinicians should not prescribe a medication that will potentially worsen one of the conditions, if avoiding it is at all possible. This article reviews the effects of diabetes medications on heart failure outcomes.

Spinal cord injury (SCI) is a complex disease that affects not only sensory and motor pathways below the neurological level of injury (NLI) but also all the organs and systems situated below this NLI. This multisystem impairment implies comprehensive management in dedicated SCI specialized centers, by interdisciplinary and multidisciplinary teams, able to treat not only the neurological impairment, but also all the systems and organs affected. After a brief history of the Spinal Cord Medicine, the author describes how to determine the level and severity of a SCI based on the International Standards for Neurological Classification of Spinal Cord Injury and the prognosis factors of recovery. This article provides also a review of the numerous SCI-related impairments (except for urinary, sexual problems and pain treated separately in this issue), their principles of management and related complications.

Objective: Few studies have evaluated the rapid progression of carotid stenosis on a large scale. We created a custom software algorithm to analyze an electronic medical record database to examine the natural progression of carotid stenosis, identify a subset of patients with rapid progression, and evaluate the specific patient risk factors associated with this rapid progression. Methods: Patients in a large integrated healthcare system who had undergone two or more carotid ultrasound scans from August 2010 to August 2018 were identified. We did not distinguish between those with an established carotid stenosis diagnosis and those with a screening ultrasound scan. We used our novel algorithm to extract data from their carotid ultrasound reports. The degrees of carotid stenosis were categorized as follows: level 1, 0% to 39%; level 2, 40% to 59%; level 3, 60% to 79%; level 4, 80% to 99%; and level 5, complete occlusion. The primary endpoint was rapid vs slow progression of carotid stenosis, with rapid progression defined as an increase of two or more levels within any 18-month period of the study, regardless of the date of the initial ultrasound scan. The association of the demographic and clinical characteristics with rapid progression was assessed by univariable and multivariable logistic regression. Results: From a cohort of 4.4 million patients, we identified 4982 patients with two or more carotid ultrasound scans and a median follow-up period of 13.1 months (range, 0.1-93.7 months). Of the 4982 patients, 879 (17.6%) had shown progression of carotid stenosis. Only 116 patients (2.3%) had had progression to level 4 (80%-99% stenosis) from any starting level during a median of 11.5 months. A total of 180 patients (3.6%) were identified as experiencing rapid progression during a median follow-up of 9.9 months. The final multivariable analysis showed that younger age (P 4 million patient records, we found that rapid progression of carotid stenosis appears to be rare. Although 17.6% of patients showed any degree of progression, only 3.6% had experienced rapid progression. Among those with any disease progression, 20.5% had experienced rapid progression. Although the overall incidence of rapid progression was low, patients with any progression might warrant close follow-up, especially if they have the associated risk factors for rapid progression. The custom software algorithm might be a powerful tool for creating and evaluating large datasets.

Background Major prevention trials for Alzheimer’s disease (AD) are now focusing on multidomain lifestyle interventions. However, the exact combination of behavioral factors related to AD pathology remains unclear. In 2 cohorts of cognitively unimpaired individuals at risk of AD, we examined which combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle (years of education or lifetime cognitive activity) related to the pathological hallmarks of AD, amyloid-β, and tau deposits. Methods A total of 115 older adults with a parental or multiple-sibling family history of sporadic AD (PREVENT-AD [PRe-symptomatic EValuation of Experimental or Novel Treatments for AD] cohort) underwent amyloid and tau positron emission tomography and answered several questionnaires related to behavioral attributes. Separately, we studied 117 mutation carriers from the DIAN (Dominant Inherited Alzheimer Network) study group cohort with amyloid positron emission tomography and behavioral data. Using partial least squares analysis, we identified latent variables relating amyloid or tau pathology with combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle. Results In PREVENT-AD, lower neuroticism, neuropsychiatric burden, and higher education were associated with less amyloid deposition (p = .014). Lower neuroticism and neuropsychiatric features, along with higher measures of openness and extraversion, were related to less tau deposition (p = .006). In DIAN, lower neuropsychiatric burden and higher education were also associated with less amyloid (p = .005). The combination of these factors accounted for up to 14% of AD pathology. Conclusions In the preclinical phase of both sporadic and autosomal dominant AD, multiple behavioral features were associated with AD pathology. These results may suggest potential pathways by which multidomain interventions might help delay AD onset or progression.

Importance: The difficulty associated with concealing keloids located in the face and neck regions often results in disfigurement and psychological stress for patients. Objective: The purpose of this review is to determine if specific regions on the head and neck have a greater propensity to develop keloids to alert the facial plastic surgeon of regional keloid risk. Evidence Review: PubMed, Ovid, Cochrane, and Embase computerized searches were performed through January 2020. Two independent reviewers conducted data extraction following a predetermined protocol identifying 1445 keloid studies. Findings: The prevalence of keloids in different regions of the head and neck was evaluated among 1598 head and neck keloids in the final analysis. Three of nine studies evaluated keloids specific to the ear and described a combined 1194 ear keloids locations (53.0% lobule, 22.9% cartilaginous region, 0.3% both, and 23.7% unspecified). One study reported exclusively on 82 neck keloids 72% of which were located in the submental or submandibular region. The remaining five studies evaluated 322 head and neck keloids more generally and showed 70.2% ear, 9.6% unspecified, 6.5% peri-/postauricular, 5.6% beard area, 2.2% scalp/forehead, 2.2% chin, 1.6% lateral face, 1.6% neck, and 0.3% central face keloids. Conclusions and Relevance: The ear, periauricular regions, bearded facial regions, and submandibular and submental sites show the highest propensity for keloid development in the head and neck region. The lowest keloid risk occurred in the central face region. Risk factors in relation to facial and neck regions associated with the formation of keloids should be taken into consideration before performing elective procedures in keloid susceptible individuals.

Epiphrenic diverticulum is a rare and benign condition with significant surgical morbidity and evolving surgical management. The objective of this study was to analyze short-term clinical outcomes after surgery for epiphrenic diverticula. We conducted a retrospective cohort study in a single tertiary care center of all patients who underwent treatment for epiphrenic esophageal diverticula from June 1990 to December 2016. Data collection included demographics, operative details and short-term outcomes (esophageal leak, other complications, 30-day mortality). In addition, all preoperative imaging was reviewed by an esophageal radiologist in order to describe epiphrenic diverticula characteristics in a uniform and blinded manner. Of the 94 patients in the study, 84 patients were managed with an open surgical approach and 10 with minimally invasive techniques. Median size of diverticula was 5.5 cm and mean height above gastroesophageal junction was 4 cm. A myotomy was completed in 95% of patients and a fundoplication in 58%. The MIS group had a shorter length of stay (4 vs 6 days). Overall complication rate was 27% with an esophageal leak rate of 7% with 60% grade I leaks that sealed with conservative management. Complete resection of the diverticulum, closure of the muscle over the resection, contralateral myotomy, and consideration for partial fundoplication are common strategies utilized to surgically treat patients with epiphrenic diverticulum. Minimally invasive approaches are increasingly utilized.

Controversy exists in the literature regarding the possible prognostic implications of the nasopharyngeal SARS-CoV-2 viral load. We carried out a retrospective observational study of 169 patients, 96 (58.9%) of whom had a high viral load and the remaining had a low viral load. Compared with patients with a low viral load, patients with a high viral load did not exhibit differences regarding preexisting cardiovascular risk factors or comorbidities. There were no differences in symptoms, vital signs, or laboratory tests in either group, except for the maximum cardiac troponin I (cTnI), which was higher in the group with a higher viral load (24 [interquartile range 9.5–58.5] versus 8.5 [interquartile range 3–22.5] ng/L, P = 0.007). There were no differences in the need for hospital admission, admission to the intensive care unit, or the need for mechanical ventilation in clinical management. In-hospital mortality was greater in patients who had a higher viral load than in those with low viral load (24% versus 10.4%, P = 0.029). High viral loads were associated with in-hospital mortality in the binary logistic regression analysis (odds ratio: 2.701, 95% Charlson Index (CI): 1.084–6.725, P = 0.033). However, in an analysis adjusted for age, gender, CI, and cTnI, viral load was no longer a predictor of mortality. In conclusion, an elevated nasopharyngeal viral load was not a determinant of in-hospital mortality in patients with COVID-19, as much as age, comorbidity, and myocardial damage determined by elevated cTnI are.

In Vietnam and around the world, Staphylococcus aureus remains a major hazard of food safety and food poisoning. S. aureus is present in many places and easily contaminates food production during processing chains. In this study, we successfully isolated S. aureus strains from suspected samples of two food borne poisoning outbreaks in Ha Giang and Vinh Phuc in 2017 and 2018, respectively. The collected samples were examined for presence of staphylococcal enterotoxins (SEs) by using 3MTMTECRATM Staph Enterotoxin kit, from there all the samples were positive with SEs. Different strains of S. aureus were isolated and then confirmed by MALDI-TOF technique. Those strains then were stored in Brain heart solution with 15% glycerol until further analysis. Our results identified three STs, ST96, ST88 (spa type t7558), and ST72 (spa type t3092), were responsible for two outbreaks. Two virulence genes detected from the above strains were sea and sec. Furthermore, these strains are test for antibiotic resistance susceptibility with commonly antibiotics. Penicillin are found to be resisted by all three STs, in particularly, ST96 and ST88 are both resistant to erythromycin while ST72 is resistant to gentamicin. Taken together, our study highlights the usefulness of molecular characterization to study and monitor bacterial pathogens associated with food poisoning outbreaks in Vietnam.

Long working hours have been shown to negatively impact adverse events in health care. In this study, a retrospective correlational design was used to evaluate the relationship between working hours and near-miss medication error alerts. During a two-year period, 5372 nurses triggered 420,706 near-miss alerts on 9, 285, 786 medication administrations. Nurses who worked 60 h or more in a week yielded an average near-miss rate of 4.0% compared to 3.0% (

Several studies have stablished discriminant formulas (DF) from red blood cell (RBC) data as simple, low time-consuming and inexpensive tools to differentiate β-thalassemia trait (β-TT) from iron deficiency anaemia (IDA). The aim of this work is to introduce new formulas and evaluate them in the differentiation of microcytic anaemia (MA) into either β-TT or IDA in the Mediterranean region of Tarragona. A total of 200 anonymized haematological determinations with MA were collected, 100 diagnosed of β-TT and 100 diagnosed of IDA. The cut-off values of new formulas were designed to differentiate β-TT from IDA groups and their diagnostic performance were compared with other published indices. Specifically, Martin-Sanchez index (MSI-I) = (%Micro-R/MCV) * MCHC * Hb and MSI-II = Hb * (MCHC + %Micro-R)/10. In addition, a new score: MSI-score = MCHC + MSI-I + MSI-II was proposed and evaluated in a transversal study with 200 patients. In our region, MSI-II index and MSI-score have demonstrated the best AUC and Youden’s index (YI) (AUC = 0.956, YI = 81%; AUC = 0.971, YI = 87%, respectively) to discriminate β-TT from IDA groups. In summary, the new MSI-score with the highest AUC, the highest YI and the best percentage (93.5%) of correctly identified patients could be used as an efficient and robust tool in microcytic anaemia mass-screening programs in this region.

Acute ischemic stroke is a neurological emergency with a high likelihood of morbidity, mortality, and long-term disability. Modern stroke care involves multidisciplinary management by neurologists, radiologists, neurosurgeons, and anesthesiologists. Current American Heart Association/American Stroke Association (AHA/ASA) guidelines recommend thrombolytic therapy with intravenous (IV) alteplase within the first 3-4.5 hours of initial stroke symptoms and endovascular mechanical thrombectomy within the first 16-24 hours depending on specific inclusion criteria. The anesthesia and critical care provider may become involved for airway management due to worsening neurologic status or to enable computerized tomography (CT) or magnetic resonance imaging (MRI) scanning, to facilitate mechanical thrombectomy, or to manage critical care of stroke patients. Existing data are unclear whether the mechanical thrombectomy procedure is best performed under general anesthesia or sedation. Retrospective cohort trials favor sedation over general anesthesia, but recent randomized controlled trials (RCT) neither suggest superiority nor inferiority of sedation over general anesthesia. Regardless of anesthesia type, a critical element of intraprocedural stroke care is tight blood pressure management. At different phases of stroke care, different blood pressure targets are recommended. This narrative review will focus on the anesthesia and critical care providers' roles in the management of both perioperative stroke and acute ischemic stroke with a focus on anesthetic management for mechanical thrombectomy.

Primary pulmonary artery sarcoma (PAS) is extremely rare in children. Nevertheless, distinguishing primary PAS from pulmonary embolism is critical to a child's survival. Primary PAS is commonly misdiagnosed as a pulmonary embolism due to similar presenting symptoms and radiographic findings. However, compared to adults, pulmonary embolism is rare in children, especially in patients who do not have predisposing factors or hypercoagulable state. We present a child with primary PAS which mimicked pulmonary embolism on presentation but eventually was resected and is doing well 5 years after resection. In the absence of predisposing factors or hypercoagulable state, solid tumors such as primary PAS should be considered when assessing a pediatric patient with presumed pulmonary embolism.

Background: Hypertension is a major risk factor for cardiovascular disease (CVD). Despite advances in hypertension prevention and treatment, the proportion of patients who are aware, treated and controlled is low, particularly in low-income and middle-income countries (LMICs). We will evaluate an adapted version of a multilevel and multicomponent hypertension control program in Guatemala, previously proven effective and feasible in Argentina. The program components are: protocol-based hypertension treatment using a standardized algorithm; team-based collaborative care; health provider education; health coaching sessions; home blood pressure monitoring; blood pressure audit; and feedback.Methods: Using a hybrid type 2 effectiveness-implementation design, we will evaluate clinical and implementation outcomes of the multicomponent program in Guatemala over an 18-month period. Through a cluster randomized trial, we will randomly assign 18 health districts to the intervention arm and 18 to enhanced usual care across five departments, enrolling 44 participants per health district and 1584 participants in total. The clinical outcomes are (1) the difference in the proportion of patients with controlled hypertension (< 130/80 mmHg) between the intervention and control groups at 18 months and (2) the net change in systolic and diastolic blood pressure from baseline to 18 months. The context-enhanced Reach, Efficacy, Adoption, Implementation, Maintenance (RE-AIM)/Practical Robust Implementation and Sustainability Model (PRISM) framework will guide the evaluation of the implementation at the level of the patient, provider, and health system. Using a mixed-methods approach, we will evaluate the following implementation outcomes: acceptability, adoption, feasibility, fidelity, adaptation, reach, sustainability, and cost-effectiveness.Discussion: We will disseminate the study findings, and promote scale up and scale out of the program, if proven effective. This study will generate urgently needed data on effective, adoptable, and sustainable interventions and implementation strategies to improve hypertension control in Guatemala and other LMICs. Fil: Paniagua Avila, Alejandra. Columbia University; Estados Unidos Fil: Fort, Meredith P.. Institute Of Nutrition Of Central America And Panamá; Guatemala Fil: Glasgow, Russell E.. University of Colorado; Estados Unidos Fil: Gulayin, Pablo Elías. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Hernández Galdamez, Diego. institute of Nutrition of Central America and Panamá; Guatemala Fil: Mansilla, Kristyne. institute of Nutrition of Central America and Panamá; Guatemala Fil: Palacios, Eduardo. Ministerio de Salud y Asistencia Social; Guatemala Fil: Peralta, Ana Lucia. Institute of Nutrition of Central America and Panamá ; Guatemala Fil: Roche, Dina. Institute of Nutrition of Central America and Panamá ; Guatemala Fil: Rubinstein, Adolfo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina Fil: He, Jiang. University Translational Science Institute; Estados Unidos Fil: Ramirez Zea, Manuel. Institute of Nutrition of Central America and Panamá ; Guatemala Fil: Irazola, Vilma. Instituto de Efectividad Clínica y Sanitaria; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

This investigation assessed 106 consecutive primary proximal interphalangeal joint arthroplasties performed on border digits: 73 index or 33 little fingers. This was compared with 193 arthroplasties performed in non-border digits: 121 middle or 72 ring fingers. There were 20 proximal interphalangeal joint arthroplasties in the border digits that required revision surgery for pain and stiffness (10 digits), dislocation (six digits), implant fracture (one digit), and infection (three digits). Risk of revision surgery was not associated with border digit. The 5-year implant survival rate for the border digits was 81%. There was no significant difference in implant revision rate or joint dislocations between border and non-border digits. We conclude that proximal interphalangeal joint arthroplasties performed in border digits had similar pain relief, survivorship, complications, and reoperation rates compared with those performed in non-border digits.Level of evidence: IV

Background Eccentric hamstring strength seems important in reducing the odds of future hamstring injuries. While age and previous injury are well-known risk factors for future hamstring injuries, the association of age and previous hamstring injury with eccentric hamstring strength in the following season is unknown. Purpose To investigate the association of age and previous hamstring injury with preseason eccentric hamstring strength in soccer players, and to investigate the association between previous hamstring injury duration and preseason eccentric hamstring strength. Study design Descriptive, cross-sectional study. Methods A convenience sample of 284 male amateur soccer players (age 18-38 years) was included in the analyses. Self-reported information about previous season hamstring injury and its duration (three weeks or less; more than three weeks) was collected. Preseason eccentric hamstring strength was obtained during the Nordic hamstring exercise using a field-based device. Results Age had a negative association with preseason eccentric hamstring strength with 0.9% reduction per year. Players with a previous hamstring injury duration of more than three weeks (n=27) had 13% lower preseason eccentric hamstring strength compared to players without previous hamstring injury. Conclusion Older players have lower preseason eccentric hamstring strength than younger players. Players with a previous hamstring injury duration of more than three weeks have lower preseason eccentric hamstring strength than the rest of the players. These results highlight the need to monitor and address the identified weaknesses in eccentric hamstring strength in amateur soccer players, with specific emphasis on older players with a previous hamstring injury of longer duration. Level of evidence 2b.

Trauma anesthesiology is a unique and growing subspecialty. With the growing number of adult and pediatric trauma centers in the United States, a thorough understanding of the early management of severely injured patients with trauma is an important aspect of anesthesia. Trauma anesthesiology requires the ability to adapt to different work environments, including the trauma bay, the operating room, and even the intensive care unit, where a patient room may require conversion to an operating suite for emergencies. This article provides a review of the anesthetic management for patients with extensive trauma, focusing on physiology, pharmacology, and bedside management.

Introduction and objectives Haptoglobin is a protein involved in the protection against oxidative damage caused by iron in haemoglobin. This protein is polymorphic, with 3 isomorphs prevalent in the population. The carriers of the Hp2-2 isoform have a lower antioxidant capacity and, in the population with diabetes, an increased risk of subclinical vascular disease and cardiovascular complications. The objective of this study was to evaluate whether this isomorphy is associated with an increased risk of carotid arteriosclerosis in subjects with and without diabetes, and free of cardiovascular disease. Patients and methods A study was conducted in a population between 45 and 74 years of age, randomly selected from the northwest area of Madrid. The participants were characterised in terms of their glycaemic status by oral glucose overload and the determination of the concentration of Hb1Ac. The haptoglobin phenotypes in all of them were determined by means of an immunoenzymatic assay, and the presence of carotid arteriosclerosis by ultrasound. Results Of the 1256 participants included in the present analysis (mean age 61.6 ± 6 years, 41.8% males), the distribution of the isoforms of haptoglobin was as follows: Hp1-1: 13.3%, Hp1-2: 48.5%, and Hp2-2: 38.2%. In comparison with subjects Hp1-1 and Hp1-2, those with the Hp2-2 phenotype had a higher prevalence of dyslipidaemia (53.3% vs 43%; p Conclusion Subjects with the Hp2-2 phenotype of haptoglobin have a higher prevalence of carotid arteriosclerosis, which is independent of the presence of other cardiovascular risk factors and their glycaemic status.

Background: In the early phases of the 2019 novel coronavirus (COVID-19) pandemic, health system leaders faced the urgent task of translating the unknown into forecasting models for hospital capacity. Our study objective was to demonstrate the application of a practical, locally informed model to estimate the hospital capacity needed even though the community COVID-19 caseload was unknown. Methods: We developed a susceptible-infected-recovered (SIR) model that was adopted from the University of Pennsylvania COVID-19 Hospital Impact Model for Epidemics and employed at 8 hospitals within Ochsner Health, the largest integrated delivery system in Louisiana, between March 16 and April 15, 2020. Intensive care unit (ICU) admissions of cases in the New Orleans area were used to estimate the community case load when testing was delayed. Results: Initially, the observed ICU census trended near R0=2.0, whereas the ventilator census trended between R0=2.0 and 3.0. After implementing social distancing, both the ICU and ventilator capacity trended toward R0=1.3, while non-ICU medical/surgical beds trended toward R0=1.5. The model accurately predicted peak ICU (n=250) and hospital bed (n=487) usage by April 6, 2020. In response to model trends, Ochsner added 130 ICU beds across its hospitals by opening a new ICU and converting operating rooms and parts of emergency departments to ICU beds. Conclusion: When disease testing is limited or results are delayed, ICU admissions data can inform SIR models of the rate of spread of COVID-19 in a community. Our model used various R0 plots to demonstrate an array of scenarios to guide planning for hospital and political leaders.

Aims The outpatient diuretic dose is a marker of diuretic resistance and prognosis in chronic heart failure (HF). Still, the impact of the preadmission dose on diuretic efficiency (DE) and prognosis in acute HF is not fully known. Methods and results We conducted an observational and prospective study. All patients admitted for acute HF treated with intravenous diuretic and at least one criterion of congestion on admission were evaluated. Decongestion [physical examination, hemoconcentration, N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) change, and lung ultrasound], DE (weight loss and urine output per unit of 40 mg furosemide), and urinary sodium were monitored on the fifth day of admission. DE was dichotomized into high–low based on the median value. A multivariate Cox regression analysis was conducted to find predictors of HF readmission or mortality. A total of 105 patients were included between July 2017 and July 2019. Mean age was 74.5 ± 12.0 years, 64.8% were male, 33.3% had de novo HF, and mean left ventricular ejection fraction was 46 ± 17%. Median follow‐up was 26 [15–35] months. Low DE based on weight loss was associated with a higher previous dose of furosemide (odds ratio [OR] 1.01 [1.00–1.02]), thiazide treatment before admission (OR 9.37 [2.19–40.14]), and lower diastolic blood pressure (OR 0.95 [0.91–0.98]) in the multivariate regression model. Only previous dose of furosemide (OR 1.01 [1.00–1.02]) and haemoglobin at admission (OR 0.76 [0.58–0.99]) were associated with low DE based on urine output in the multivariate analysis. The correlation between the previous dose of furosemide and DE based on weight loss was poor (r = −0.12; P = 0.209) and with DE based on urine output was weak to moderate (r = −0.33; P 80 mg in ADHF identified patients with particularly poor prognosis (log‐rank

Red blood cells in sickle cell anemia (sRBC) are more heterogeneous in their physical properties than healthy red blood cells, spanning adhesiveness, rigidity, density, size, and shape. sRBC with increased adhesiveness to the vascular wall would trigger vaso-occlusive like complications, a hallmark of sickle cell anemia. We investigated whether segregation occurs among sRBC flowing in micron-sized channels and tested the impact of aggregation on segregation. Two populations of sRBC of different densities were separated, labeled, and mixed again. The mixed suspension was flowed within glass capillary tubes at different pressure-drops, hematocrit, and suspending media that promoted or not cell aggregation. Observations were made at a fixed channel position. The mean flow velocity was obtained by using the cells as tracking particles, and the cell depleted layer (CDL) by measuring the distance from the cell core border to the channel wall. The labeled sRBC were identified by stopping the flow and scanning the cells within the channel section. The tube hematocrit was estimated from the number of fluorescence cells identified in the field of view. In non-aggregating media, our results showed a heterogeneous distribution of sRBC according to their density: low-density sRBC population remained closer to the center of the channel, while the densest cells segregated towards the walls. There was no impact of the mean flow velocity and little impact of hematocrit. This segregation heterogeneity could influence the ability of sRBC to adhere to the vascular wall and slow down blood flow. However, promoting aggregation inhibited segregation while CDL thickness was enhanced by aggregation, highlighting a potential protective role against vaso-occlusion in patients with sickle cell anemia.

International audience; The Rhône-Loire metropolitan areas’ 2020/21 respiratory syncytial virus (RSV) epidemic was delayed following the implementation of non-pharmaceutical interventions (NPI), compared with previous seasons. Very severe lower respiratory tract infection incidence among infants ≤ 3 months decreased twofold, the proportion of cases among children aged > 3 months to 5 years increased, and cases among adults > 65 years were markedly reduced. NPI appeared to reduce the RSV burden among at-risk groups, and should be promoted to minimise impact of future RSV outbreaks.

The COVID-19 pandemic has had a profound impact on the healthcare system worldwide, which led to a decrease in the number of melanoma diagnosis,1 but the consequences of lockdown on newly diagnosed melanomas severity have not been widely reported. We aimed to evaluate how the first lockdown in France impacted the incidence and prognostic characteristics of new melanomas, in our skin cancer center in the Parisian region, highly affected by the pandemic.

American Indian and Alaska Native (AI/AN) people suffer a disproportionate burden of diabetes and cardiovascular disease. Urban Indian Health Organizations (UIHOs) are an important source of diabetes services for urban AI/AN people. Two evidence-based interventions—diabetes prevention (DP) and healthy heart (HH)–have been implemented and evaluated primarily in rural, reservation settings. This work examines the capacity, challenges and strengths of UIHOs in implementing diabetes programs.Methods: We applied an original survey, supplemented with publicly-available data, to assess eight organizational capacity domains, strengths and challenges of UIHOs with respect to diabetes prevention and care. We summarized and compared (Fisher's and Kruskal-Wallis exact tests) items in each organizational capacity domain for DP and HH implementers vs. non-implementers and conducted a thematic analysis of strengths and challenges.Results: Of the 33 UIHOs providing services in 2017, individuals from 30 sites (91% of UIHOs) replied to the survey. Eight UIHOs (27%) had participated in either DP (n = 6) or HH (n = 2). Implementers reported having more staff than non-implementers (117.0 vs. 53.5; p = 0.02). Implementers had larger budgets, ~$10 million of total revenue compared to $2.5 million for non-implementers (p = 0.01). UIHO strengths included: physical infrastructure, dedicated leadership and staff, and community relationships. Areas to strengthen included: staff training and retention, ensuring sufficient and consistent funding, and data infrastructure.Conclusions: Strengthening UIHOs across organizational capacity domains will be important for implementing evidence-based diabetes interventions, increasing their uptake, and sustaining these interventions for AI/AN people living in urban areas of the U.S.

BACKGROUND This study systematically investigated circulating and retinal tissue lipid determinants of human diabetic retinopathy (DR) to identify underlying lipid alterations associated with severity of DR. METHODS Retinal tissues were retrieved from postmortem human eyes, including 19 individuals without diabetes, 20 with diabetes but without DR, and 20 with diabetes and DR, for lipidomic study. In a parallel study, serum samples from 28 American Indians with type 2 diabetes from the Gila River Indian Community, including 12 without DR, 7 with mild nonproliferative DR (NPDR), and 9 with moderate NPDR, were selected. A mass-spectrometry–based lipidomic platform was used to measure serum and tissue lipids. RESULTS In the postmortem retinas, we found a graded decrease of long-chain acylcarnitines and longer-chain fatty acid ester of hydroxyl fatty acids, diacylglycerols, triacylglycerols, phosphatidylcholines, and ceramide(NS) in central retina from individuals with no diabetes to those with diabetes with DR. The American Indians’ sera also exhibited a graded decrease in circulating long-chain acylcarnitines and a graded increase in the intermediate-length saturated and monounsaturated triacylglycerols from no DR to moderate NPDR. CONCLUSION These findings suggest diminished synthesis of complex lipids and impaired mitochondrial β-oxidation of fatty acids in retinal DR, with parallel changes in circulating lipids. TRIAL REGISTRATION ClinicalTrials.gov NCT00340678. FUNDING This work was supported by NIH grants R24 DK082841, K08DK106523, R03DK121941, P30DK089503, P30DK081943, P30DK020572, P30 EY007003; The Thomas Beatson Foundation; and JDRF Center for Excellence (5-COE-2019-861-S-B).

Background Cardiac troponin is independently associated with cardiovascular events and mortality in patients with chronic kidney disease (CKD). Their joint effect is yet to be clarified. Purpose This study aims to evaluate the prognostic implication of myocardial injury and CKD in patients attended in an emergency room. Methods Retrospective study carried out between January 2012 and December 2013 with consecutive patients attended in an emergency room with troponin determination, who were distributed into four cohorts according to positive troponin and/or glomerular filtration rate (GFR) Results 3622 patients were included (median age 68.5 years [IQR 55.5–79.5]; 43% were women). Compared to subjects with normal GFR, the 565 subjects with CKD were significantly older (80.5 vs 66.5 years), with worse cardiovascular profile (arterial hypertension: 87% vs 56%; diabetes mellitus: 46% vs 22%) and greater comorbidity (history of myocardial infarction: 29% vs 18%; heart failure: 17% vs 5%; peripheral vascular disease: 16% vs 5%; cerebrovascular disease: 13% vs 7%%). Myocardial injury was also related to elderly and worse cardiovascular profile and comorbidity, especially in normal GFR subjects. 23.5% (718 subjects) of normal GFR subjects presented with myocardial injury. This percentage was much higher in the presence of renal impairment (331 subjects, 58.6%). Troponin was associated with a higher risk of death (both in-hospital and during follow-up) and of readmission due to infarction or heart failure, regardless of GFR. The reference cohort in the multivariate competing risk mode was that with subjects without myocardial injury or kidney disease. This analysis showed the worst MACE (all-cause death, non-fatal myocardial infarction and heart failure admission) in four-year follow-up in patients with renal impairment and positive troponin (HR 3.94, 95% CI 3.317–4.682), second worst MACE in those with myocardial injury and with normal GFR (HR 2.408, 95% CI 2.064–2.811), and then abnormal GFR patients with negative troponin (HR 1.532, 95% CI 1.220–1.923). Patients with both myocardial injury and renal impairment had the highest mortality (HR 4.633, 95% CI 3.829–5.604) and more readmissions for heart failure (HR 2.163, 95% CI 1.647–2.841). The myocardial-injury-and-normal-GFR cohort showed significantly higher mortality than the renal-impairment-with-negative-troponin cohort (HR 2.669 vs HR 1.794), more heart failure (HR 1.951 vs 1.067) and more myocardial infarctions (HR 2.439 vs 1.235) in the follow-up. Conclusion The results suggest that myocardial injury has better predictive power than chronic kidney disease for MACE events and also for individually mortality, readmission for heart failure or myocardial infarction. Funding Acknowledgement Type of funding sources: None.

Background Diabetes and myocardial injury are clinical conditions associated with cardiovascular events and increased mortality during follow-up. It is not known to what extent both conditions enhance their prognostic effect in patients seen in the emergency room with cardiac troponin determination. Purpose This study aims to evaluate the prognostic implication of diabetes and myocardial injury in patients attended in the emergency room with cardiac troponin determination. Methods Retrospective observational cohorts study, in which all the patients attended the emergency room from January 2012 and December 2013 with a troponin determination. The sample was categorized according to the diabetes mellitus condition and myocardial injury (troponin below 99 th), studying four groups: non-diabetic without myocardial injury (G1), diabetic without myocardial injury (G2), non-diabetic with myocardial injury (G3), and diabetic with myocardial injury (G4). Baseline clinic characteristics and prognostic data were studied with a four years follow-up. Results A total of 3622 patients were studied; 924 (25'55%) diabetics. Three hundred seventy-one diabetic patients (40% of all diabetic patients) had an elevated troponin determination, while six hundred seventy-eights non-diabetic patients had elevated troponin (25'13% from all non-diabetics). Diabetic patients were significantly older (mean age 74 vs. 67 years). They had more frequently history of hypertension (81'9% vs 53'2%), acute myocardial infarction (31'6% vs 15'8%), heart failure (11'1% vs 5'7%), peripheral vascular disease (11'1% vs 5'2%), cerebrovascular disease (11'4% vs 6'6%), chronic pulmonary disease (23'3% vs 16'2%) and renal impairment (16'8% vs 5'2%). At four years of follow-up, G2, G3 and G4 had higher mortality than G1 (HR (95IC): 1,352 (1,080–1,693), 2,896 (2,896–3,477), and 3,441 (2,809–4,216), respectively). A multivariate competing risk model was used to obtain the HRs for readmission for myocardial infarction and heart failure between G2, G3 and G4 in relation to G1 (HR (IC 95%) 2,511 (1,592–3,96), 2,682 (1,739–4,138) and 5,036 (3,221–7,876), respectively for myocardial infarction, and 2,663 (1,825–3,886), 2,562 (1,753–3,744) and 4,292 (2,936–6,274) respectively for heart failure). Conclusions Both conditions, myocardial injury, and diabetes have a prognostic impact at a long-term follow-up with a cumulative effect, being the troponin elevation, a better prognostic marker of death risk, and similar to diabetes history for the risk of myocardial infarction and heart failure. Funding Acknowledgement Type of funding sources: None. ICC hospitalization cumulativeincidenceIAM cumulative incidence

The biomarkers α-fetoprotein (AFP), Lens culinaris agglutinin-reactive AFP fraction (AFP-L3), and des-γ-carboxy prothrombin (DCP) have emerging implications in hepatocellular carcinoma (HCC) surveillance, overall prognosis, and post-surgical recurrence risk. This retrospective study investigated treatment and bridge to liver transplant (LT) prognosis associated with AFP, AFP-L3%, and DCP biomarker profiles prior to liver-directed therapy (LDT). In a 140-patient cohort, each biomarker was associated with HCC progression risk using the established thresholds of AFP &gt, 20 ng/mL, AFP-L3 &gt, 15%, and DCP &gt, 7.5 ng/mL. Over 60% of the cohort expressed at least one biomarker at baseline. Although most biomarker-positive patients expressed the clinical standard AFP (57/87), only 32% were positive for AFP alone. Biomarker accumulation increased HCC progression risk but was not associated with demographic factors or preserved liver function. Biomarker triple negative patients had smaller index HCC (p = 0.003), decreased multifocal burden (p = 0.010), and a higher objective response rate (ORR, 62% compared to 46%, p = 0.011). Expressing all three biomarkers at baseline was associated with dismal first-line ORR (12%) with a median time to progression (TTP) of only 181 days post-LDT. Patients with triple negative status for the HCC biomarkers AFP, AFP-L3%, and DCP have the highest first-line ORR with &lt, 5% HCC progression 1-year post-LDT. Biomarker profiling can establish baseline prognosis for identifying optimal bridge to LT and downstaging to LT candidates with triple negative biomarker status and providing an ideal post-LDT target as a compliment to radiographic response.

Aim Several papers have analysed the clinical benefits and safety of Virtual Fracture Clinics (VFCs). A significant increase in the use of Trauma and Orthopaedic (T&O) VFCs was seen during the COVID-19 pandemic. This study aims to investigate the social impact of VFCs on the travel burden and travel costs of T&O patients, as well as the potential environmental benefits in relation to fuel consumption and travel-related pollutant emissions. Method All patients referred for T&O VFC review from March 2020 to June 2020 were retrospectively analysed. The travel burden and environmental impacts of hypothetical face-to-face consultations were compared with these VFC reviews. The primary outcomes measured were patient travel time saved, patient travel distance saved, patient cost savings and reduction in air-pollutant emissions. Results Over a four-month period, 1359 VFC consultations were conducted. The average travel distance saved by VFC review was 88.6 kilometres (range 3.3-615), with an average of 73 minutes (range 9-390) of travel-time saved. Patients consumed, on average, 8.2 litres (range 0.3-57.8) less fuel and saved an average of €11.02 (range 0.41-76.59). The average reduction in air-pollutant vehicle emissions, including carbon dioxide, carbon monoxide, nitric oxides and volatile organic compounds was 20.3 kilograms (range 0.8-140.8), 517.3 grams (g) (range 19.3-3592.3), 38.1g (range 1.4-264.8) and 56.9g (range 2.1-395.2), respectively. Conclusions VFCs reduce patient travel distance, travel time and travel costs. In addition, VFCs confer significant environmental benefits through reduced fuel consumption and reduction of harmful environmental emissions.

Background: Although obstructive sleep apnea (OSA) could act as a modulator of clinical severity in sickle cell disease (SCD), few studies focused on the associations between the two diseases.Research Question: The aims of this study were: (1) to explore the associations between OSA, nocturnal oxyhemoglobin saturation (SpO2) and the history of several acute/chronic complications, (2) to investigate the impact of OSA and nocturnal SpO2 on several biomarkers (hematological, blood rheological, and coagulation) in patients with SCD.Study Design and Methods: Forty-three homozygous SCD patients underwent a complete polysomnography recording followed by blood sampling.Results: The proportion of patients suffering from nocturnal hypoxemia did not differ between those with and those without OSA. No association between OSA and clinical severity was found. Nocturnal hypoxemia was associated with a higher proportion of patients with hemolytic complications (glomerulopathy, leg ulcer, priapism, or pulmonary hypertension). In addition, nocturnal hypoxemia was accompanied by a decrease in RBC deformability, enhanced hemolysis and more severe anemia.Interpretation: Nocturnal hypoxemia in SCD patients could be responsible for changes in RBC deformability resulting in enhanced hemolysis leading to the development of complications such as leg ulcers, priapism, pulmonary hypertension or glomerulopathy.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT03753854.

In mammals including humans, the convention defining rapid-eye-movement (REM) sleep — also called paradoxical sleep — states that it is mainly characterized by a low voltage fast electrocortical rhythms, rapid eye movements and a muscle atonia occasionally accompanied by brief distal twitches. When facing sleep pathologies, all these criteria are not always met and identifying REM sleep becomes thus a challenge. Here we review such criteria and report the adjustments proposed to identify and measure REM sleep in animal models of sleep pathologies such as REM sleep Behaviour Disorder and narcolepsy type 1. We also argue that video-recordings synchronized to multi-parametric polysomnography are mandatory to recognize REM sleep and differentiate it from dissociated states in animal models of sleep disorders.

DAISY combined Supercritical Angle Fluorescence (SAF) detection in order to provide an absolute axial reference to a point spread function engineering approach . The dual view optical setup permits to introduce a strong astigmatism and decouple lateral and axial information, thus extending the axial performances without degrading the lateral precision. This technique provides 3D absolute information over a 1-µm capture range above the glass coverslip and an axial localization precision down to 15 nm with minimal loss of lateral resolution and little sensitivity to field aberrations. We will present sequential and simultaneous up to 3 color 3D imaging in cells.

Psychological morbidity, sexuality, and health/system information have been identified as the highest areas of support needs in patients undergoing management of their prostate cancer (PCa). Management of a patient's sexual function prior to, during and after PCa radiotherapy requires multidisciplinary coordination of care between radiation oncologists, urologists, dermatologists, pharmacists, and psychiatrists. The finale of this three-part review provides a framework for clinicians to better understand the role of mental healthcare providers in the management of sexual toxicities associated with prostatic radiotherapy. The authors recommend that patients be referred for psychological evaluation and possibly to individual, couples or group general or cognitive behavioral sex therapy at the time of their PCa diagnosis, for a more specialized focus on management of sexual toxicities and sexual recovery. The importance and implications of the masculine self-esteem, sexual orientation, gender identification, cultural expectations, relationship status and patient education are reviewed. Well-informed patients tend to have a better quality of life outcomes compared to patients that take on a passive role in their cancer management.

Background This study aimed to investigate the clinical features and prognosis of diabetes and myocardial injury in patients admitted to the emergency department. Methods We analyzed the clinical data of all consecutive patients admitted to the emergency department during the years 2012 and 2013 with at least 1 cardiac Troponin I (cTnI Ultra Siemens, Advia Centaur) determination, and were classified according to the status of diabetes mellitus (DM) and myocardial injury (MI). Clinical events were evaluated in a 4-year follow-up. Results A total of 3622 patients were classified according to the presence of DM (n = 924 (25.55%)) and MI (n = 1049 (28.96%)). The proportion of MI in patients with DM was 40% and 25% in patients without DM. Mortality during follow-up was 10.9% in non-DM patients without MI, 21.3% in DM patients without MI, 40.1% in non-DM patients with MI, and 52.8% in DM patients with MI. A competitive risk model was used to obtain the Hazard Ratio (HR) for readmission for myocardial infarction or heart failure. There was a similar proportion of readmission for myocardial infarction and heart failure at a four-year follow-up in patients with DM or MI, which was much higher when DM was associated with MI, with respect to patients without DM or MI. The HR (95% Coefficient Interval) for myocardial infarction in the DM without MI, non-DM with MI, and DM with MI groups with respect to the non-DM without MI group was 2511 (1592–3960), 2682 (1739–4138), and 5036 (3221–7876), respectively. The HR (95% CI) for the risk of readmission for heart failure in the DM without MI, non-DM with MI, and DM with MI groups with respect to the non-DM without MI group was 2663 (1825–3886), 2562 (1753–3744) and 4292 (2936–6274), respectively. Conclusions The association of DM and MI in patients treated in an Emergency Service identifies patients at very high risk of mortality and cardiovascular events.

We aimed to develop two models to estimate first AMI and stroke/TIA, respectively, in type 2 diabetes mellitus patients, by applying backward elimination to the following variables: age, sex, duration of diabetes, smoking, BMI, and use of antihyperglycemic drugs, statins, and aspirin. As time-varying covariates, we analyzed blood pressure, albuminuria, lipid profile, HbA1c, retinopathy, neuropathy, and atrial fibrillation (only in stroke/TIA model). Both models were stratified by antihypertensive drugs. We evaluated 2980 patients (52.8% women; 67.3 ± 11.2 years) with 24,159 person-years of follow-up. We recorded 114 cases of AMI and 185 cases of stroke/TIA. The factors that were independently associated with first AMI were age (≥ 75 years vs. 64 mmol/mol vs. 2 decrease) (p

Background Despite its low efficacy, chemotherapy with dacarbazine remains an option in metastatic melanoma patients after failure of immune checkpoint inhibitors (ICI) ± targeted therapy. Some observations suggested an increased efficacy of chemotherapy in melanoma or lung cancer patients previously treated with ICI; we aimed to evaluate the efficacy of dacarbazine in a controlled-group study of patients pre-treated or not with ICI. Methods We retrospectively collected data from all consecutive patients treated with dacarbazine for advanced cutaneous melanoma without brain metastasis, in our skin cancer centre between June 2006 and September 2019. The primary endpoint was progression-free survival (PFS); secondary endpoints were overall response rates (ORR), overall survival (OS) and safety of dacarbazine. Results Among 72 patients, 17 (23.6%) received dacarbazine after ICI and 55 (76.3%) without prior ICI. Despite less favourable prognostic factors in patients ICI-pre-treated, median PFS was 4.27 months (range 0.89-43.69) in this group versus 2.04 months (range 1.25-39.25) P = 0.03 in non-ICI-pre-treated patients; ORR were 35.3% and 12.7%, respectively. The median OS and the occurrence of adverse events were similar in both groups. Conclusion Dacarbazine seems to offer a short-lived benefit in patients with progressive advanced disease despite ICI (±targeted therapy), and could be an alternative before considering best supportive care.

Change in cancer cell identity is well characterized as a mechanism of cancer progression and acquired resistance to targeted therapies. Lung adenocarcinoma (LUAD) exhibits significant heterogeneity in cell identity and differentiation state; these characteristics correlate directly with prognosis, response to available therapies, and acquisition of drug resistance. In previous work, we have shown that FoxA1 and FoxA2 (FoxA1/2) activate a gastric differentiation program in NKX2-1-negative LUAD. Here we investigate the role of FoxA1/2 in NKX2-1-positive LUAD. We find that FoxA1/2 are consistently expressed in NKX2-1-positive human LUAD. Foxa1/2 deletion severely impairs proliferation and significantly prolongs overall survival in a genetically engineered mouse model of KRAS-driven LUAD. FoxA1/2 activate expression of a mixed-lineage transcriptional program characterized by co-expression of pulmonary (Alveolar Type II) and gastrointestinal marker genes. Loss of FoxA1/2 causes a lineage switch, activating gene expression programs associated with Alveolar Type I cells and maturing squamous epithelial cells. Inhibition of NKX2-1 partially rescues the antiproliferative impact of FoxA1/2 loss, showing that NKX2-1 retains some degree of activity in FoxA1/2-null cells, despite its inability to activate canonical target genes. In summary, this study identifies FoxA1/2 expression as a novel vulnerability in NKX2-1 positive LUAD and shows that FoxA1/2 actively regulate cellular identity in this disease.

The chaperone and anti-apoptotic activity of α-crystallins (αA- and αB-) and their derivatives has received increasing attention due to their tremendous potential in preventing cell death. While originally known and described for their role in the lens, the upregulation of these proteins in cells and animal models of neurodegenerative diseases highlighted their involvement in adaptive protective responses to neurodegeneration associated stress. However, several studies also suggest that chronic neurodegenerative conditions are associated with progressive loss of function of these proteins. Thus, while external supplementation of α-crystallin shows promise, their potential as a protein-based therapeutic for the treatment of chronic neurodegenerative diseases remains ambiguous. The current review aims at assessing the current literature supporting the anti-apoptotic potential of αA- and αB-crystallins and its potential involvement in retinal neurodegenerative diseases. The review further extends into potentially modulating the chaperone and the anti-apoptotic function of α-crystallins and the use of such functionally enhanced proteins for promoting neuronal viability in retinal neurodegenerative disease.

Glucose-dependent insulinotropic polypeptide receptor (GIPR) is associated with obesity in human genome-wide association studies. Similarly, mouse genetic studies indicate that loss of function alleles and glucose-dependent insulinotropic polypeptide overexpression both protect from high-fat diet–induced weight gain. Together, these data provide compelling evidence to develop therapies targeting GIPR for the treatment of obesity. Further, both antagonists and agonists alone prevent weight gain, but result in remarkable weight loss when codosed or molecularly combined with glucagon-like peptide-1 analogs preclinically. Here, we review the current literature on GIPR, including biology, human and mouse genetics, and pharmacology of both agonists and antagonists, discussing the similarities and differences between the 2 approaches. Despite opposite approaches being investigated preclinically and clinically, there may be viability of both agonists and antagonists for the treatment of obesity, and we expect this area to continue to evolve with new clinical data and molecular and pharmacological analyses of GIPR function.

Diabetes adversely affects multiple organs, including the kidney, eye and nerve, leading to diabetic kidney disease, diabetic retinopathy and diabetic neuropathy, respectively. In both type 1 and type 2 diabetes, tissue damage is organ specific and is secondary to a combination of multiple metabolic insults. Hyperglycaemia, dyslipidaemia and hypertension combine with the duration and type of diabetes to define the distinct pathophysiology underlying diabetic kidney disease, diabetic retinopathy and diabetic neuropathy. Only recently have the commonalities and differences in the metabolic basis of these tissue-specific complications, particularly those involving local and systemic lipids, been systematically examined. This review focuses on recent progress made using preclinical models and human-based approaches towards understanding how bioenergetics and metabolomic profiles contribute to diabetic kidney disease, diabetic retinopathy and diabetic neuropathy. This new understanding of the biology of complication-prone tissues highlights the need for organ-specific interventions in the treatment of diabetic complications.