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Worldwide, the coronavirus 19 disease pandemic caused a worse chance of a timely diagnosis for cancer patients. We conducted a retrospective analysis of new diagnoses registered in the national pediatric oncology database, comparing the first lockdown period (March-May 2020) with the same period of 2015-2019. The total number of cases (0-19 years) dropped by 20.8% (from 441 between 2015 and 2019 to 349 in 2020). A major reduction was observed for adolescents (15-19 years) (-32.9%) and for adolescents with solid tumors (-56.4%, p = 0.03). Our data suggest that the enforced lockdown reduced the possibility for these already vulnerable patients to access the referral centers.

Background Concerns regarding long-term durability of surgical repair for functional mitral regurgitation are based on short-term data, with few comparisons of ischemic (IMR) versus non-ischemic (NIFMR) etiology. Methods 788 consecutive patients receiving mitral repair for functional mitral regurgitation were evaluated from a prospectively maintained database. Patients with other surgical procedures were included. Propensity score matching was used to compare outcomes in IMR versus NIFMR. Results Unmatched IMR patients tended to be older men with greater comorbidities. 198 matched pairs of IMR versus NIFMR patients had similar demographics with relatively preserved ejection fraction 40±13% and end-systolic diameter 4.3±1.1cm. Concomitant coronary revascularization occurred in 70% of matched IMR patients. All patients received an annuloplasty ring, usually 24-26 mm. Heart failure class improved from 2.8 preop to 1.5 at 5 years (P =2+) mitral regurgitation (27±4% v 26±4%, P=0.4), severe regurgitation (10±3% v 8±2%, P=0.5), and mitral reoperation (3±1% v 3±1%, P=0.4) were not different between IMR v NIFMR. Recurrent moderate regurgitation was associated with heart failure readmission but not with mortality. Conclusions In propensity-matched patients, IMR versus NIFMR had worse survival but similar repair durability, with moderate regurgitation in 27% at 10 years and rare severe regurgitation or mitral reoperation. In selected patients with relatively preserved function, mitral repair for IMR or NIFMR can improve symptoms with durable mild regurgitation in most patients out to 10 years.

Background and purpose Some studies have shown that air pollution, often assessed by thin particulate matter with diameter below 2.5 µg/m3 (PM2.5), may contribute to severe COVID‐19 courses, as well as play a role in the onset and evolution of multiple sclerosis (MS). However, the impact of air pollution on COVID‐19 has never been explored specifically amongst patients with MS (PwMS). This retrospective observational study aims to explore associations between PM2.5 and COVID‐19 severity amongst PwMS. Methods Data were retrieved from an Italian web‐based platform (MuSC‐19) which includes PwMS with COVID‐19. PM2.5 2016–2018 average concentrations were provided by the Copernicus Atmospheric Monitoring Service. Italian patients inserted in the platform from 15 January 2020 to 9 April 2021 with a COVID‐19 positive test were included. Ordered logistic regression models were used to study associations between PM2.5 and COVID‐19 severity. Results In all, 1087 patients, of whom 13% required hospitalization and 2% were admitted to an intensive care unit or died, were included. Based on the multivariate analysis, higher concentrations of PM2.5 increased the risk of worse COVID‐19 course (odds ratio 1.90; p = 0.009). Conclusions Even if several other factors explain the unfavourable course of COVID‐19 in PwMS, the role of air pollutants must be considered and further investigated., Air pollution, often assessed by particulate matter with diameter below 2.5 µg/m3, may contribute to severe COVID‐19 courses. 1087 patients were included, of whom 13% required hospitalization and 2% were admitted to an intensive care unit or died. Even if several other factors explain the unfavourable course of COVID‐19 in patients with multiple sclerosis, the role of air pollutants must be considered and further investigated.

Studies have shown that as age increases, parasitism could also be more frequent, on the other hand, the lack of immunity can increase the risk of infection in younger individuals. Regarding sex, there is a general tendency for males to be more parasitized than females, in the case of primates, this is related to the effort made by males into attaining and maintain a high rank, implying high levels of testosterone, a hormone with immunosuppressive effects. Immunosuppressive effects of stress hormones can also increase susceptibility in dominant or subordinate individuals, nevertheless, in a study, the level of exposure to parasites seems to be more important than the immunosuppressive effects of stress in explaining why dominant females have more infections from directly transmitted parasites. In this study, we investigated the relationship between the prevalence of Giardia spp. and Blastocystis spp. and the categories of age and sex in black and golden howler monkeys (Alouatta caraya) of Argentina. We analyzed 375 fecal samples from 27 individuals (juveniles and adults of both sexes), using microscopy and techniques of flotation and sedimentation. To analyze the relationship between age, sex, and infection prevalence, a Generalized Linear Mixed Model was used. In adults, the prevalence of infection was 78.5 % while in juveniles, all individuals (100 %) were infected with both protozoa. Males had a infection prevalence 84.6%, in females it was 92.8 %. When comparing infection prevalence between ages and between sexes, no significant differences were found (P > 0.05). Research suggests that parasite infection rates may be influenced by specific form of transmission, in this sense, these protozoa, are transmitted through ingestion of cysts which are infectious immediately after defecation has occurred. On the other hand, all members of the group tend to defecate simultaneously, leaving all the members of the group exposed to infection. Therefore, we suggest that physiological or behavioral factors do not appear to be important in the risk of protozoan infection.

Long-term continuous-flow left ventricular assist device (CFLVAD) therapy is limited by complications. Compared with stroke and renal dysfunction, post-CFLVAD bowel ischemia is poorly characterized. Adult patients who underwent first-time durable CFLVAD implantation at our institution between 2008 and 2018 were identified and screened for bowel ischemia using Current Procedural Terminology codes for abdominal surgical exploration and International Classification of Disease codes for intestinal vascular insufficiency. Patients who developed biopsy-proven bowel ischemia (cases) were matched to controls (1:1, nearest neighbor, caliper = 0.29) based on preoperative characteristics. Incidences of postoperative right heart failure and renal replacement therapy were compared using McNemar's test. One year survival was estimated using the Kaplan-Meier method. Overall, 711 patients underwent CFLVAD implantation. Nineteen (2.7%) developed bowel ischemia (cases) median 17 days postimplantation (IQR 8-71). The majority of cases were male (78.9%), Black (63.2%), received HeartMate II (57.9%), treated as destination therapy (78.9%), and had a history of hypertension (89.5%), chronic kidney disease (84.2%), hyperlipidemia (84.2%), smoking (78.9%), and atrial fibrillation (57.9%). Post-LVAD, case patients were more likely to develop moderate-severe right heart failure (89.5% vs. 68.4%, p = 0.005), require renal replacement therapy (21.1% vs. 0%, p < 0.001), and less likely to survive to discharge (52.6% vs. 89.5%, p = 0.02) compared with controls. Case subjects demonstrated worse 1 year survival. While less common than stroke and renal dysfunction, post-CFLVAD bowel ischemia is associated with high 1 year mortality. Multi-institutional registries should consider reporting abdominal complications such as bowel ischemia as an adverse event to further investigate these trends and identify predictors of this complication to reduce patient mortality.

Myocardial aging increases the cardiovascular risk in the elderly. The Receptor for Advanced Glycation End-products (RAGE) is involved in age-related disorders. The soluble isoform (sRAGE) acts as a scavenger blocking the membrane-bound receptor activation. This study aims at investigating RAGE contribution to age-related cardiac remodeling. We analyzed the cardiac function of three different age groups of female Rage-/- and C57BL/6N (WT) mice: 2.5- (Young), 12- (Middle-age, MA) and 21-months (Old) old. While aging, Rage-/- mice displayed an increase in left ventricle (LV) dimensions compared to age-matched WT animals, with the main differences observed in the MA groups. Rage-/- mice showed higher fibrosis and a larger number of α-Smooth Muscle Actin (SMA)+ cells with age, along with increased expression of pro-fibrotic Transforming Growth Factor (TGF)-β1 pathway components. RAGE isoforms were undetectable in LV of WT mice, nevertheless, circulating sRAGE declined with aging and inversely associated with LV diastolic dimensions. Human cardiac fibroblasts stimulated with sRAGE exhibited a reduction in proliferation, pro-fibrotic proteins and TGF-beta Receptor 1 (TGFbR1) expression and Smad2-3 activation. Finally, sRAGE administration to MA WT animals reduced cardiac fibrosis. Hence, our work shows that RAGE associates with age-dependent myocardial changes and indicates sRAGE as an inhibitor of cardiac fibroblasts differentiation and age-dependent cardiac fibrosis.

Purpose To suggest PTV margins for liver SBRT with different motion management strategies based on a systematic review and meta-analysis. Methods In accordance with Preferred-Reporting-Items-for-Systematic-Reviews-and-Meta-Analyses (PRISMA), a systematic review in PubMed, Embase and Medline databases was performed for liver tumor position variability. From an initial 533 studies published before October 2020, 36 studies were categorized as 18 free-breathing (FB; npatients=401), 9 abdominal compression (AC; npatients=145) and 9 breath-hold (BH; npatients=126). A meta-analysis was performed on inter- and intra-fraction position variability to report weighted-mean with 95% confidence interval (CI95) in superior-inferior (SI), left-right (LR) and anterior-posterior (AP) directions. Furthermore, weighted-mean ITV margins were computed for FB (nstudies=15, npatients =373) and AC (nstudies=6, npatients =97) and PTV margins were computed for FB (nstudies =6, npatients =95), AC (nstudies =7, npatients =106) and BH (nstudies =8, npatients =133). Results The FB weighted-mean intra-fraction variability, ITV margins and weighted-standard-deviation in mm were SI-9.7, CI95=9.3-10.1, 13.5±4.9; LR-5.4, CI95=5.3-5.6, 7.3±7.9 and AP-4.2, CI95=4.0-4.4, 6.3±7.6. The inter-fraction-based results were SI-4.7, CI95=4.3-5.1, 5.7±1.7; LR-1.4, CI95=1.1-1.6, 3.6±2.7 and AP-2.8, CI95=2.5-3.1, 4.8±2.1. For AC intra-fraction results in mm were SI-1.8, CI95=1.6-2.0, 2.6±1.2; LR-0.7, CI95=0.6-0.8, 1.7±1.5 and AP-0.9, CI95=0.8-1.0, 1.9±1.7. The inter-fraction results were SI-2.6, CI95=2.3-3.0, 5.2±2.9; LR-1.9, CI95=1.7-2.1, 4.0±2.2 and AP-2.9, CI95=2.5-3.2, 5.8±2.7. For BH the inter-fraction variability and the weighted-mean PTV margins and weighted-standard-deviation in mm were SI-2.4, CI95=2.1-2.7, 5.6±2.9; LR-1.8; CI95=1.3-2.2, 5.5±1.7 and AP-1.4; CI95=1.2-1.7, 6.1±2.1. Conclusion Our meta-analysis suggested that weighted-mean PTV margin of 6mm might be appropriate for BH. For AC and FB, asymmetric PTV margins (weighted-mean margin = 4mm (AP), 6mm (SI/LR)) might be appropriate. For FB, if larger (> ITV margin) intra-fraction variability observed, the additional intra- and inter-fraction variability should be accounted in the PTV margin.

Background There is mounting evidence on the existence of a Pediatric Inflammatory Multisystem Syndrome-temporally associated to SARS-CoV-2 infection (PIMS-TS), sharing similarities with Kawasaki Disease (KD). The main outcome of the study were to better characterize the clinical features and the treatment response of PIMS-TS and to explore its relationship with KD determining whether KD and PIMS are two distinct entities. Methods The Rheumatology Study Group of the Italian Pediatric Society launched a survey to enroll patients diagnosed with KD (Kawasaki Disease Group – KDG) or KD-like (Kawacovid Group - KCG) disease between February 1st 2020, and May 31st 2020. Demographic, clinical, laboratory data, treatment information, and patients’ outcome were collected in an online anonymized database (RedCAP®). Relationship between clinical presentation and SARS-CoV-2 infection was also taken into account. Moreover, clinical characteristics of KDG during SARS-CoV-2 epidemic (KDG-CoV2) were compared to Kawasaki Disease patients (KDG-Historical) seen in three different Italian tertiary pediatric hospitals (Institute for Maternal and Child Health, IRCCS “Burlo Garofolo”, Trieste; AOU Meyer, Florence; IRCCS Istituto Giannina Gaslini, Genoa) from January 1st 2000 to December 31st 2019. Chi square test or exact Fisher test and non-parametric Wilcoxon Mann-Whitney test were used to study differences between two groups. Results One-hundred-forty-nine cases were enrolled, (96 KDG and 53 KCG). KCG children were significantly older and presented more frequently from gastrointestinal and respiratory involvement. Cardiac involvement was more common in KCG, with 60,4% of patients with myocarditis. 37,8% of patients among KCG presented hypotension/non-cardiogenic shock. Coronary artery abnormalities (CAA) were more common in the KDG. The risk of ICU admission were higher in KCG. Lymphopenia, higher CRP levels, elevated ferritin and troponin-T characterized KCG. KDG received more frequently immunoglobulins (IVIG) and acetylsalicylic acid (ASA) (81,3% vs 66%; p = 0.04 and 71,9% vs 43,4%; p = 0.001 respectively) as KCG more often received glucocorticoids (56,6% vs 14,6%; p Conclusion Our study suggests that SARS-CoV-2 infection might determine two distinct inflammatory diseases in children: KD and PIMS-TS. Older age at onset and clinical peculiarities like the occurrence of myocarditis characterize this multi-inflammatory syndrome. Our patients had an optimal response to treatments and a good outcome, with few complications and no deaths.

Introduction The ability of an organization to accommodate a large influx of patients during a prolonged period is dependent on surge capacity. The aim of this article is to describe the surge experience with space, supplies, and staff training in response to COVID-19 and provide guidance to other organizations. Background A hospital's response to a large-scale event is greatly impacted by the ability to surge and, depending on the type of threat, to maintain a sustained response. To identify surge capacity, an organization must first consider the type of event to appropriately plan resources. Preparation process An epidemic surge drill, conducted in 2012, served as a guide in planning for the COVID-19 pandemic. The principles of crisis standards of care and a hospital incident command structure were used to clearly define roles, open lines of communication, and inform our surge plan. Preparation began by collaborating with multidisciplinary groups to acquire the most appropriate space, as well as adequate supplies, and identify and train staff. Implementation Teams were formed to identify the necessary resources to expand the intensive care unit (ICU) environment quickly and efficiently. Educational training was developed for redeployed staff. Outcomes Beth Israel Deaconess Medical Center experienced the largest surge of ICU patients within a hospital system in the state of Massachusetts. The ICU capacity was expanded by 93% from 77 to 149 beds, and the surge was maintained for approximately 9 weeks. Shadowing experiences before the actual surge were extremely valuable. Conclusions Planning for the surge of critically ill patients required a thoughtful, collaborative approach. Ongoing staff support and communication from nursing leadership were necessary to ensure safe, effective care for critically ill patients in a new and dynamic environment.

Background and study aims Endoscope reprocessing has been associated with a variable failure rate. Our aim was to present an overview on current practices for reprocessing in Italian facilities and discuss the principle critical points.Methods In 2014 the Italian Society for Digestive Diseases implemented an accreditation program in collaboration with an independent organization for certification and with the Italian Association for Endoscopy Technical Operators. During a 1-day site visit of the endoscopy center, two endoscopists, one nurse, and the representative of the certification body evaluated the endoscope reprocessing.Results As of July 1, 2020, 28 endoscopy centers had been accredited. Ten centers are completing the measures to correct deficiencies found at the visit. Three centers withdrew from the program. The accreditation program has found variations between the various centers, confirming the poor compliance with guidelines. Major deviations from the standards, established by the model before the site visit according to national and international guidelines, concerned instrument cleaning (44.7 % of the centers), instrument storage (23.7 %), and microbiological tests (31.6 %).Conclusions Our overview demonstrated the lack of many reprocessing phases, which are important to prevent endoscopy-associated infections. Accreditation can achieve a transformation in quality and safety of reprocessing with the Italian centrally-led approach.

Aims We aim to determine any additional benefit of virtual reality (VR) experience if compared to conventional cross-sectional imaging and standard three-dimensional (3D) modelling when deciding on surgical strategy in patients with complex double outlet right ventricle (DORV). Methods and results We retrospectively selected 10 consecutive patients with DORV and complex interventricular communications, who underwent biventricular repair. An arterial switch operation (ASO) was part of the repair in three of those. Computed tomography (CT) or cardiac magnetic resonance imaging images were used to reconstruct patient-specific 3D anatomies, which were then presented using different visualization modalities: 3D pdf, 3D printed models, and VR models. Two experienced paediatric cardiac surgeons, blinded to repair performed, reviewed each case evaluating the suitability of repair following assessment of each visualization modalities. In addition, they had to identify those who had ASO as part of the procedure. Answers of the two surgeons were compared to the actual operations performed. There was no mortality during the follow-up (mean = 2.5 years). Two patients required reoperations. After review of CT/cardiac magnetic resonance images, the evaluators identified the surgical strategy in accordance with the actual surgical plan in 75% of the cases. When using 3D pdf this reached only 70%. Accordance improved to 85% after revision of 3D printed models and to 95% after VR. Use of 3D printed models and VR facilitated the identification of patients who required ASO. Conclusion Virtual reality can enhance understanding of suitability for biventricular repair in patients with complex DORV if compared to cross-sectional images and other 3D modelling techniques.

Supplemental Digital Content is available in the text., The study aim was to examine the impact time in therapeutic range (TTR, International Normalized Ratio [INR] 2.0–3.0) has on survival and adverse events in patients receiving the HeartWare HVAD System in the ENDURANCE and ENDURANCE Supplemental Trials. Evaluable subjects (n = 495) had >1 INR value recorded 1–24 months postimplant and were categorized as: low TTR (10–39%), moderate TTR (40–69%), and high TTR (≥70%). Baseline characteristics, adverse events, and survival were analyzed. Low TTR patients experienced higher rates of major bleeding (1.69 vs. 0.54 events per patient year [EPPY]; p < 0.001), GI bleeding (1.22 vs. 0.38 EPPY; p < 0.001), stroke (0.47 vs. 0.17 EPPY; p < 0.001), thrombus requiring exchange (0.05 vs. 0.01 EPPY; p = 0.02), infection (1.44 vs. 0.69 EPPY; p < 0.001), and renal dysfunction (0.23 vs. 0.05 EPPY; p < 0.001) compared with high TTR. Moderate TTR had higher rates of major bleeding (0.75 vs. 0.54 EPPY; p < 0.001), thrombus requiring exchange (0.05 vs. 0.01 EPPY; p = 0.007), cardiac arrhythmia (0.32 vs. 0.24 EPPY; p = 0.04), and infection (0.90 vs. 0.69 EPPY; p = 0.001) compared with high TTR. Two year survival was greater among moderate and high versus low cohorts (Log-rank p = 0.001). The significant reduction in morbidity and mortality in destination therapy (DT) HVAD patients with well-controlled TTR (≥70%) emphasizes the importance of vigilant anticoagulation management.

International audience; Despite widespread hearing problems among older adults, only a minority uses hearing aids. The stigma associated with such aids represents a key factor modulated by language. The purpose of this study is to analyze the impact of different forms of media communication on both implicit and explicit attitudes toward hearing aids. A preliminary analysis highlighted an over-representation of “technical” and “medical” terms in the corpus linguistic commonly used by the press. These results were used to design an online experimental study. The results suggested that the exposure to a language that includes informal words—as opposed to the technical terms commonly used by the press—favors positive implicit and explicit attitudes toward hearing aids, particularly among people who have direct contact with older adults. Overall, the use of an informal language in the press could generate a style of communication that positively influences people’s attitudes toward hearing aids.

The incidence of graft-versus-host disease (GVHD) after cord blood (CB) transplantation (CBT) is lower than expected given the marked degree of human leukocyte antigen (HLA)-mismatch of CB grafts. While the exact mechanism that underlies this biology remains unclear, it is hypothesized to be due to the low number of mostly immature T-cells infused as part of the graft1,2, and increased tolerance of CB-derived lymphocytes induced by the state of pregnancy. Nevertheless, acute GVHD (aGVHD) is a significant complication of CBT. In contrast, the incidence of chronic GVHD (cGVHD) following CBT is lower than what is observed following matched related or unrelated donor HSC transplantation (HSCT)3-6. This review outlines the guidelines for the prevention and management of acute and chronic GVHD following CBT.

A dramatic disorder tentatively attributed to diencephalic-hypothalamic damage or dysfunction, dysautonomia affects recovery from brain injury. Its incidence, correlation with etiology, and relevance as a predictor of outcome were retrospectively surveyed in 333 patients in vegetative state (VS) for more than 2 weeks at admission. Outcome was assessed according to the Glasgow Outcome Scale (GOS). Data were treated statistically by multivariate analyses. Dysautonomia occurred in 26.1% of patients, with greater incidence among post-traumatic (31.9%) than non-traumatic (15.8%) patients. Outcome was worse among non-traumatic than post-traumatic patients irrespective of dysautonomia, and worst among non-traumatic patients with dysautonomia. Dysautonomia proved common among patients in VS (with incidence depending on etiology and age) and influenced the patients' outcome through mechanisms still to be defined, but conceivably mediated by diencephalic-hypothalamic unbalance.

Background Left ventricular assist devices (LVAD) are increasingly used for durable mechanical circulatory support in advanced heart failure. While LVAD therapy provides substantial improvement in mortality and quality of life, long-term therapy confers increased risk for device complications. We evaluated if cardiac computed tomography (CCT) improves the detection of cardiomechanical complications among patients with LVAD and suspected device malfunction. Methods In this study, we compared the diagnostic performance of CCT and transthoracic echocardiography (TTE) for the identification of cardiomechanical LVAD complications, including thrombus or neointimal hyperplasia, inflow cannula malposition with dynamic obstruction, fixed outflow obstruction, device infection, and severe aortic regurgitation. Complications were confirmed with surgical evaluation, pathologic assessment, or response to therapeutic intervention. Results Among 58 LVAD patients, who underwent CCT and TTE for suspected LVAD dysfunction, there were 49 confirmed cardiomechanical LVAD complications among 43 (74.1%) patients. The most common LVAD complication was thrombus or neointimal hyperplasia (65.3%), followed by dynamic obstruction (26.5%). Individually, CCT identified 29 of the 49 (59.2%) confirmed LVAD cardiomechanical complications, whereas TTE alone identified a complication in 11 cases (22.4%). However, diagnostic performance was greatest when the two modalities were used in combination, yielding a sensitivity of 67%, specificity of 93%, PPV of 97%, NPV of 47% and diagnostic accuracy of 73%. Conclusion The novel and complementary use of CCT with TTE for the evaluation of suspected device malfunction improves the accurate identification of cardiomechanical LVAD complication compared to either modality alone.

PurposeStereotactic body radiation therapy (SBRT) has become the standard of care for inoperable early-stage non-small cell lung cancer and is often used for recurrent lung cancer and pulmonary metastases. Radiation-induced lung toxicity (RILT), including radiation pneumonitis and pulmonary fibrosis, is a major concern for which it is important to understand dosimetric and clinical predictors.Methods and materialsThis study was undertaken through the American Association of Physicists in Medicine's Working Group on Biological Effects of Stereotactic Body Radiotherapy. Data from studies of lung SBRT published through the summer of 2016 that provided detailed information about RILT were analyzed.ResultsNinety-seven studies were ultimately considered. Definitions of the risk organ and complication endpoints as well as dose-volume information presented varied among studies. The risk of RILT, including radiation pneumonitis and pulmonary fibrosis, was reported to be associated with the size and location of the tumor. Patients with interstitial lung disease appear to be especially susceptible to severe RILT. A variety of dosimetric parameters were reported to be associated with RILT. There was no apparent threshold "tolerance dose-volume" level. However, most studies noted safe treatment with a rate of symptomatic RILT of

BACKGROUND: In the era of antiretroviral therapy, HIV-positive patients have reduced mortality from HIV infection and increased morbidity from end stage heart failure. The number of HIV-positive heart transplantation recipients remains scant. Long-term survival has not been rigorously studied. We compared survival outcomes of heart transplantation in HIV-positive recipients to HIV-negative recipients. METHODS: Clinical data from all adult heart transplantations were extracted from the UNOS Dataset. The impact of recipient HIV status was analyzed with Cox proportional hazards modeling, 1:3 propensity score matching and Kaplan-Meier survival analysis. RESULTS: Seventy-five HIV-positive recipients and 29,848 HIV-negative recipients were identified. Race distributions differed between the recipient groups, with Blacks comprising a larger proportion of the HIV-positive recipient group (46.7% versus 20.9%, p

As an alternative stem cell source, cord blood (CB) has many advantages. However, delayed engraftment, lack of transferred immunity, and a significant incidence of acute graft-versus-host disease renders CB transplant (CBT) recipients at high risk of infectious complications. This guidance written by CBT and infectious disease experts outlines evidence-based recommendations for the prevention and treatment of opportunistic infections in adult patients undergoing CBT. Topics addressed include bacterial, fungal, viral, pneumocystis jirovcii and toxoplasmosis prophylaxis, suggested PCR monitoring for viruses, therapy for the most commonly encountered infections after CBT. We review key concepts including the recent important role of letermovir in the prevention of CMV reactivation. In instances where there is a paucity of data, practice recommendations are provided, including the duration of antimicrobial prophylaxis.

OBJECTIVE: Conventional ultrafiltration (CUF) during cardiopulmonary bypass (CPB) serves to hemoconcentrate blood volume to avoid allogeneic blood transfusions. Previous studies have determined weight-indexed CUF volumes as a continuous variable are associated with postoperative AKI after cardiac surgery but optimal weight-indexed volumes that predict AKI have not been described. DESIGN: Retrospective cohort SETTING: Single-center university hospital PARTICIPANTS: 1,641 consecutive patients that underwent elective cardiac surgery between June 2013-December 2015. INTERVENTIONS: CUF volume was removed during CPB in all participants as part of our routine practice. We investigated the association of dichotomized weight indexed CUF volume removal with postoperative AKI development to provide pragmatic guidance for clinical practice at our institution. MEASUREMENTS AND MAIN RESULTS: Primary outcomes of postoperative AKI was defined by the KDIGO staging criteria and dichotomized, weight indexed CUF volumes (ml/kg) were defined by (i) extreme quartiles (Q3) and by (ii) Youden’s criterion that best predicted AKI development. Multivariable logistic regression models were developed to test the association of these dichotomized indices with AKI status. Postoperative AKI occurred in 827 patients (50.4%). Higher CUF volumes were associated with AKI development by quartiles (CUF >Q(3)=32.6 vs. CUF 32 mL/kg increased the risk for postoperative AKI development. Importantly, CUF volume removal of any amount did not mitigate allogeneic blood transfusion during elective cardiac surgery. Prospective studies are needed to validate these findings.

For cord blood transplantation (CBT), appropriate patient and conditioning regimen selection is necessary to achieve long-term disease-free survival. This review aims to provide comprehensive guidelines on these issues using evidence from the literature and experience at dedicated CBT centers. Topics include patient and disease characteristics that make CBT a good or poor choice and a review of outcomes in commonly used conditioning regimens in CBT. This is accompanied with recommendations on regimen intensity based on disease, organ function, and patient performance status and age. In addition, the use of antithymocyte globulin in CBT is discussed, as is the choice of conditioning in aplastic anemia patients who have access to acceptable CB units.

Objective Markers of seizure recurrence are needed to personalize antiseizure medication (ASM) therapy. In the clinical practice, EEG features are considered to be related to the risk of seizure recurrence for genetic generalized epilepsies (GGE). However, to our knowledge, there are no studies analyzing systematically specific EEG features as indices of ASM efficacy in GGE. In this study, we aimed at identifying EEG indicators of ASM responsiveness in Juvenile Myoclonic Epilepsy (JME), which, among GGE, is characterized by specific electroclinical features. Methods We compared the features of prolonged ambulatory EEG (paEEG, 22 h of recording) of JME patients experiencing seizure recurrence within a year (“cases”) after EEG recording, with those of patients with sustained seizure freedom for at least 1 year after EEG (“controls”). We included only EEG recordings of patients who had maintained the same ASM regimen (dosage and type) throughout the whole time period from the EEG recording up to the outcome events (which was seizure recurrence for the “cases”, or 1‐year seizure freedom for “controls”). As predictors, we evaluated the total number, frequency, mean and maximum duration of epileptiform discharges (EDs) and spike density (i.e. total EDs duration/artifact‐free EEG duration) recorded during the paEEG. The same indexes were assessed also in standard EEG (stEEG), including activation methods. Results Both the maximum length and the mean duration of EDs recorded during paEEG significantly differed between cases and controls; when combined in a binary logistic regression model, the maximum length of EDs emerged as the only valid predictor. A cut‐off of EDs duration of 2.68 seconds discriminated between cases and controls with a 100% specificity and a 93% sensitivity. The same indexes collected during stEEG lacked both specificity and sensitivity. Significance The occurrence of prolonged EDs in EEG recording might represent an indicator of antiepileptic drug failure in JME patients.

Polatuzumab vedotin is approved therapy in the United States for relapsed/refractory diffuse large B-cell lymphoma in combination with bendamustine and rituximab (Pola+BR). However, the safety and efficacy of Pola+BR outside of a clinical trial setting is unknown.We analyzed use of pola-based therapy at 5 centers in the United States, including dose, response rates, progression-free survival (PFS), survival, and toxicity.Sixty-nine patients with aggressive B-cell lymphoma, including 66 with diffuse large B-cell lymphoma/high-grade B-cell lymphoma and 84% refractory to prior therapy, were treated. Responses occurred in of 50%, including 24% complete response. Median duration of response was 5.1 months, PFS was 2.0 months, and survival was 5.3 months, at 4 months median follow-up. Inferior PFS was associated with prior refractory disease (median, 57 days vs. not reached; P = .003) and lack of response to Pola+BR (PFS, 27 days vs. 152 days; P .001). Discontinuation owing to planned cellular therapy was seen in 36% and owing to toxicity occurred in 12%; unplanned hospitalizations occurred in 36%.We conclude that commercial Pola is applied to highly refractory lymphomas at our centers, often with intent to bridge to subsequent therapy. Although some clinical benefit was observed, efficacy was inferior to clinical trial data, especially among those with refractory disease.

Objective: This study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on the severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (PwMS). Methods: We retrospectively collected data of PwMS with suspected or confirmed COVID-19. All the patients had complete follow-up to death or recovery. Severe COVID-19 was defined by a 3-level variable: mild disease not requiring hospitalization versus pneumonia or hospitalization versus intensive care unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated with severe COVID-19 by multivariate and propensity score (PS)-weighted ordinal logistic models. Sensitivity analyses were run to confirm the results. Results: Of 844 PwMS with suspected (n = 565) or confirmed (n = 279) COVID-19, 13 (1.54%) died; 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty-eight (4.5%) were admitted to an ICU; 99 (11.7%) had radiologically documented pneumonia; 96 (11.4%) were hospitalized. After adjusting for region, age, sex, progressive MS course, Expanded Disability Status Scale, disease duration, body mass index, comorbidities, and recent methylprednisolone use, therapy with an anti-CD20 agent (ocrelizumab or rituximab) was significantly associated (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.18–4.74, p = 0.015) with increased risk of severe COVID-19. Recent use (

Made available in DSpace on 2022-04-29T08:35:59Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-12-01 Division of Intramural Research, National Institute of Allergy and Infectious Diseases Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases National Institute of Allergy and Infectious Diseases National Center for Advancing Translational Sciences National Heart, Lung, and Blood Institute National Institute of Environmental Health Sciences U.S. National Library of Medicine National Institute of Neurological Disorders and Stroke Division of Cancer Prevention, National Cancer Institute Neurological complications worsen outcomes in COVID-19. To define the prevalence of neurological conditions among hospitalized patients with a positive SARS-CoV-2 reverse transcription polymerase chain reaction test in geographically diverse multinational populations during early pandemic, we used electronic health records (EHR) from 338 participating hospitals across 6 countries and 3 continents (January–September 2020) for a cross-sectional analysis. We assessed the frequency of International Classification of Disease code of neurological conditions by countries, healthcare systems, time before and after admission for COVID-19 and COVID-19 severity. Among 35,177 hospitalized patients with SARS-CoV-2 infection, there was an increase in the proportion with disorders of consciousness (5.8%, 95% confidence interval [CI] 3.7–7.8%, pFDR < 0.001) and unspecified disorders of the brain (8.1%, 5.7–10.5%, pFDR < 0.001) when compared to the pre-admission proportion. During hospitalization, the relative risk of disorders of consciousness (22%, 19–25%), cerebrovascular diseases (24%, 13–35%), nontraumatic intracranial hemorrhage (34%, 20–50%), encephalitis and/or myelitis (37%, 17–60%) and myopathy (72%, 67–77%) were higher for patients with severe COVID-19 when compared to those who never experienced severe COVID-19. Leveraging a multinational network to capture standardized EHR data, we highlighted the increased prevalence of central and peripheral neurological phenotypes in patients hospitalized with COVID-19, particularly among those with severe disease. Department of Biostatistics Epidemiology and Informatics University of Pennsylvania Perelman School of Medicine Department of Biomedical Informatics Harvard Medical School Department of Neurology University of Pittsburgh, Biomedical Science Tower 3, Suite 7014, 3501 5th Avenue Department of Pediatrics Wake Forest School of Medicine Department of Critical Care National University Health Systems Department of Preventive Medicine Northwestern University Department of Biomedical Informatics University of Pittsburgh Department of Surgery National University Health Systems Department of Internal Medicine University of Kansas Medical Center Data Analytics Center University of Pennsylvania Health System Department of Computational Medicine and Bioinformatics University of Michigan Department of Biomedical Informatics University of Kentucky Department of Legal Economic and Social Sciences University Magna Graecia of Catanzaro Health Catalyst INC. Department of Surgery ASST Pavia Lombardia Region Health System Clinical Research Unit of Botucatu Medical School São Paulo State University Pediatric Emergency Department Hôpital Necker-Enfants Malades Assistance Publique-Hôpitaux de Paris National Center for Infectious Diseases Tan Tock Seng Hospital Departments of Biomedical Informatics Pediatrics Cincinnati Children’s Hospital Medical Center University of Cincinnati Department of Pediatrics Medical University of South Carolina Department of Surgery St. Luke’s University Health Network Department of Medicine David Geffen School of Medicine at UCLA UOC Ricerca Innovazione e Brand Reputation ASST Papa Giovanni XXIII Department of Electrical Computer and Biomedical Engineering University of Pavia IT Department Innovation & Data APHP Greater Paris University Hospital I.T. Department ASST Pavia Health Informatics Hospital Universitario, 12 de Octubre Strategy and Transformation Department APHP Greater Paris University Hospital Faculty of Medicine and Medical Center University of Freiburg Digital Research Informatics and Virtual Environments (DRIVE), Great Ormond Street Hospital for Children Scientific Direction IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano North Carolina Translational and Clinical Sciences (NC TraCS) Institute University of North Carolina BIOMERIS (BIOMedical Research Informatics Solutions) Department of Biomedical Informatics HEGP APHP Greater Paris University Hospital Department of Medical and Surgical Sciences Data Analytics Research Center University Magna Graecia of Catanzaro Department of Anesthesia St. Luke’s University Health Network Université Paris-Saclay Inria CEA INRIA Sophia-Antipolis–ZENITH Team LIRMM Computational Health Informatics Program Boston Children’s Hospital Department of Internal Medicine University of Kentucky Unit of Internal Medicine and Endocrinology Istituti Clinici Scientifici Maugeri SpA SB IRCCS Department of Internal Medicine and Therapeutics University of Pavia Informatics Institute University of Alabama at Birmingham IAM Unit Bordeaux University Hospital/ERIAS-Inserm U1219 BPH Biomedical Informatics Center Medical University of South Carolina Clinical Research Informatics Boston Children’s Hospital Department of Biomedical and Health Informatics Children’s Hospital of Philadelphia SED/SIERRA Inria Centre de Paris Health Information Technology & Services University of Michigan Internal Medicine Department Botucatu Medical School São Paulo State University Heinrich-Lanz-Center for Digital Health University Medicine Mannheim Heidelberg University Department of Anesthesiology Critical Care and Pain Medicine Boston Children’s Hospital Department of Learning Health Sciences University of Michigan Medical School MSHI Medical University of South Carolina Department of Medicine Massachusetts General Hospital Division of Human Genetics Department of Pediatrics The Children’s Hospital of Philadelphia Center for Medical Information and Communication Technology University Hospital Renaissance Computing Institute/Department of Computer Science University of North Carolina Clinical Research Unit Saint Antoine Hospital APHP Greater Paris University Hospital Clevy.io Department of Biostatistics Harvard T.H. Chan School of Public Health VA Informatics and Computing Infrastructure VA Salt Lake City Health Care System MICHR Informatics University of Michigan Laboratory of Informatics and Systems Engineering for Clinical Research Istituti Clinici Scientifici Maugeri SpA SB IRCCS Harvard Catalyst Harvard Medical School Clinical Research Unit Paris Saclay APHP Greater Paris University Hospital Department of Anesthesiology and Critical Care Children’s Hospital of Philadelphia VA Informatics and Computing Infrastructure Tennessee Valley Healthcare System Veterans Affairs Medical Center École Normale Supérieure PSL Université Paris BIG-ARC The University of Texas Health Science Center at Houston School of Biomedical Informatics Pediatric Infectious Disease Department Hospital Universitario, 12 de Octubre Department of Infectious Diseases Great Ormond Street Hospital for Children Department of Neurology Massachusetts General Hospital Internal Medicine Department of Botucatu Medical School São Paulo State University Department of Pediatrics Boston Children’s Hospital Center for Biomedical Informatics Wake Forest School of Medicine Department of Medical Informatics University of Erlangen-Nürnberg Department of Veterans Affairs Office of Research and Development Biomedical Data Science Lab ITACA Institute Universitat Politècnica de València Nurse Department of FMB-Medicine School of Botucatu Management Engineering ASST Pavia Lombardia Region Health System Department of Anesthesiology University Hospital Erlangen FAU Erlangen-Nürnberg Critical Care Medicine Department of Medicine St. Luke’s University Health Network Department of Medicine National University Hospital Department of Information Management Chang Gung University Clinical & Translational Science Institute Medical College of Wisconsin Montréal Neurological Institute McGill University SequeL Inria Lille Respiratory Department ICS S Maugeri IRCCS Department of Health Management and Informatics University of Missouri Department of Oncology ASST Papa Giovanni XXIII Clinical Research Unit of Botucatu Medical School São Paulo State University Internal Medicine Department Botucatu Medical School São Paulo State University Internal Medicine Department of Botucatu Medical School São Paulo State University Division of Intramural Research, National Institute of Allergy and Infectious Diseases: AI11679 Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases: AI11679 National Institute of Allergy and Infectious Diseases: AI11679 National Center for Advancing Translational Sciences: CTSA Award #UL1TR001878 National Center for Advancing Translational Sciences: CTSA Award #UL1TR002366 National Heart, Lung, and Blood Institute: K23HL148394 National Institute of Environmental Health Sciences: P30ES017885 U.S. National Library of Medicine: R01LM012095 National Institute of Neurological Disorders and Stroke: R01NS098023 Division of Cancer Prevention, National Cancer Institute: U24CA210967 National Center for Advancing Translational Sciences: UL1TR001420 National Center for Advancing Translational Sciences: UL1TR001857

Synthetic lethality is an innovative framework for discovering novel anticancer drug candidates. One example is the use of PARP inhibitors (PARPi) in oncology patients with BRCA mutations. Here, we exploit a new paradigm based on the possibility of triggering synthetic lethality using only small organic molecules (dubbed "fully small-molecule-induced synthetic lethality"). We exploited this paradigm to target pancreatic cancer, one of the major unmet needs in oncology. We discovered a dihydroquinolone pyrazoline-based molecule (35d) that disrupts the RAD51-BRCA2 protein-protein interaction, thus mimicking the effect of BRCA2 mutation. 35d inhibits the homologous recombination in a human pancreatic adenocarcinoma cell line. In addition, it synergizes with olaparib (a PARPi) to trigger synthetic lethality. This strategy aims to widen the use of PARPi in BRCA-competent and olaparib-resistant cancers, making fully small-molecule-induced synthetic lethality an innovative approach toward unmet oncological needs.

The combination of COVID-19 vaccination with immunotherapy by checkpoint inhibitors in cancer patients could intensify immunological stimulation with potential reciprocal benefits. Here, we examine more closely the possible adverse events that can arise in each treatment modality. Our conclusion is that caution should be exercised when combining both treatments.

BACKGROUND AND OBJECTIVE: To quantify and compare the vessel density (VD) in the superficial capillary plexus (SCP) and the deep capillary plexus (DCP), as well as the size of the foveal avascular zone (FAZ) in patients with proliferative diabetic retinopathy (PDR) before and after panretinal photocoagulation (PRP). PATIENTS AND METHODS: This prospective clinical study was conducted in the Department of Ophthalmology, Miulli Hospital Acquaviva delle Fonti, Italy. Each patient underwent measurement of best-corrected visual acuity (BCVA), fluorescein angiography, spectral-domain optical coherence tomography (OCT), and OCT angiography (OCTA) at baseline. Patients received PRP within 7 days from baseline, using frequency-doubled Nd:YAG pattern scan laser. BCVA and OCTA were repeated at 1 month and at 6 months. Repeated measure one-way analysis of variance was used to investigate differences between OCTA parameters before and after PRP. RESULTS: Eighteen eyes of 14 patients with diabetes (11 males, 78.6%) were enrolled. Patients underwent a mean of four laser treatments. BCVA was slightly worse at baseline (0.30 ± 0.20) compared to the visual function after 6 months (0.25 ± 0.24; P = .3). FAZ (0.33 ± 0.19 mm 2 vs. 0.33 ± 0.16 mm 2 ; P = .6), foveal SCP (16.4 ± 8.0 vs. 16.5 ± 6.5; P = .4), foveal DCP (28.5 ± 8.6 vs. 28.2 ± 8.1; P = .8), parafoveal SCP (38.4 ± 5.7 vs. 38.6 ± 4.5; P = .9), and parafoveal DCP (46.1 ± 5.2 vs. 43.8 ± 5.1; P = .3) did not change 6 months after PRP. CONCLUSIONS: OCTA parameters were not significantly affected by peripheral laser treatment at both short- (1-month) and medium- / long-term (6-month) follow-up. Further analysis with larger samples and longer duration is warranted to confirm these results. [ Ophthalmic Surg Lasers Imaging Retina . 2019;50:174–178.]

We compared outcomes in 603 patients with myelodysplastic syndrome (MDS) after HLA-haploidentical relative (n = 176) and HLA-matched unrelated (n = 427) donor hematopoietic cell transplantation (HCT) from 2012 to 2017, using the Center for International Blood and Marrow Transplant Research database. All transplantations used reduced-intensity conditioning regimens. Total-body irradiation plus cyclophosphamide and fludarabine was the predominant regimen for HLA-haploidentical relative donor HCT, and graft-versus-host disease (GVHD) prophylaxis was uniformly posttransplantation cyclophosphamide, calcineurin inhibitor, and mycophenolate. Fludarabine with busulfan or melphalan was the predominant regimen for HLA-matched unrelated donor HCT, and GVHD prophylaxis was calcineurin inhibitor with mycophenolate or methotrexate. Results of multivariate analysis revealed higher relapse (hazard ratio [HR], 1.56; P = .0055; 2-year relapse rate, 48% vs 33%) and lower disease-free survival (DFS) rates after HLA-haploidentical relative donor HCT (HR, 1.29; P = .042; 2-year DFS, 29% vs 36%). However, overall survival (OS) rates did not differ between donor type (HR, 0.94; P = .65; 2-year OS, 46% for HLA-haploidentical and 44% for HLA-matched unrelated donor HCT) because of mortality associated with chronic GVHD. Acute grade 2 to 4 GVHD (HR, 0.44; P < .0001) and chronic GVHD (HR, 0.36; P < .0001) were lower after HLA-haploidentical relative donor HCT. By 2 years, probability of death resulting from chronic GVHD was lower after HLA-haploidentical relative compared with HLA-matched unrelated donor HCT (6% vs 21%), negating any potential survival advantage from better relapse control. Both donor types extend access to transplantation for patients with MDS; strategies for better relapse control are desirable for HLA-haploidentical relative donor HCT, and effective GVHD prophylaxis regimens are needed for unrelated donor HCT.

Aims The aortic valve (AV) neocuspidization (Ozaki procedure) is a novel surgical technique for AV disease that preserves the natural motion and cardiodynamics of the aortic root. In this study, we sought to evaluate, by 4D-flow magnetic resonance imaging, the aortic blood flow characteristics after AV neocuspidization in paediatric patients. Methods and results Aortic root and ascending aorta haemodynamics were evaluated in a population of patients treated with the Ozaki procedure; results were compared with those of a group of patients operated with the Ross technique. Cardiovascular magnetic resonance studies were performed at 1.5 T using a 4D flow-sensitive sequence acquired with retrospective electrocardiogram-gating and respiratory navigator. Post-processing of 4D-flow analysis was performed to calculate flow eccentricity and wall shear stress. Twenty children were included in this study, 10 after Ozaki and 10 after Ross procedure. Median age at surgery was 10.7 years (range 3.9–16.5 years). No significant differences were observed in wall shear stress values measured at the level of the proximal ascending aorta between the two groups. The analysis of flow patterns showed no clear association between eccentric flow and the procedure performed. The Ozaki group showed just a slightly increased transvalvular maximum velocity. Conclusion Proximal aorta flow dynamics of children treated with the Ozaki and the Ross procedure are comparable. Similarly to the Ross, Ozaki technique restores a physiological laminar flow pattern in the short-term follow-up, with the advantage of not inducing a bivalvular disease, although further studies are warranted to evaluate its long-term results.

Whether to repair nonsevere tricuspid regurgitation (TR) during surgery for ischemic mitral valve regurgitation (IMR) remains uncertain.The goal of this study was to investigate the incidence, predictors, and clinical significance of TR progression and presence of ≥moderate TR after IMR surgery.Patients (n = 492) with untreated nonsevere TR within 2 prospectively randomized IMR trials were included. Key outcomes were TR progression (either progression by ≥2 grades, surgery for TR, or severe TR at 2 years) and presence of ≥moderate TR at 2 years.Patients' mean age was 66 ± 10 years (67% male), and TR distribution was 60% ≤trace, 31% mild, and 9% moderate. Among 2-year survivors, TR progression occurred in 20 (6%) of 325 patients. Baseline tricuspid annular diameter (TAD) was not predictive of TR progression. At 2 years, 37 (11%) of 323 patients had ≥moderate TR. Baseline TR grade, indexed TAD, and surgical ablation for atrial fibrillation were independent predictors of ≥moderate TR. However, TAD alone had poor discrimination (area under the curve, ≤0.65). Presence of ≥moderate TR at 2 years was higher in patients with MR recurrence (20% vs. 9%; p = 0.02) and a permanent pacemaker/defibrillator (19% vs. 9%; p = 0.01). Clinical event rates (composite of ≥1 New York Heart Association functional class increase, heart failure hospitalization, mitral valve surgery, and stroke) were higher in patients with TR progression (55% vs. 23%; p = 0.003) and ≥moderate TR at 2 years (38% vs. 22%; p = 0.04).After IMR surgery, progression of unrepaired nonsevere TR is uncommon. Baseline TAD is not predictive of TR progression and is poorly discriminative of ≥moderate TR at 2 years. TR progression and presence of ≥moderate TR are associated with clinical events. (Comparing the Effectiveness of a Mitral Valve Repair Procedure in Combination With Coronary Artery Bypass Grafting [CABG] Versus CABG Alone in People With Moderate Ischemic Mitral Regurgitation, NCT00806988; Comparing the Effectiveness of Repairing Versus Replacing the Heart's Mitral Valve in People With Severe Chronic Ischemic Mitral Regurgitation, NCT00807040).

Background: To date, no study has been performed on the relationship between depression and perimenopausal symptoms using the Path model in Iran. Objective: This study aims to assess the relationship between depression and menopause symptoms using the PATH model. Methods: A cross-sectional study was conducted for 4 months, in 2019, and 332 menopausal women were enrolled in 14 public health centers. Data collection instruments included questionnaires of demographic characteristics, anxiety instrument, Menopause Rating Scale, and the Beck Depression short Inventory (BDI-S). The hypothesized mediators were assessed using Structural Equation Modeling (SEM). The model included depression symptoms (dependent variable), anxiety (mediators), number of alive children (moderator), and menopausal symptoms (independent variable). Analyses were conducted by SPSS 16 and AMOS 20. Results: There was a significant positive correlation between menopause symptoms with total anxiety (Rs=0.52), state anxiety (Rs=0.47), trait anxiety (Rs=0.46), and depression (Rs=0.54). Depression had a significant positive correlation with total anxiety (Rs=0.64), trait anxiety (Rs=0.58), and state anxiety (Rs=0.59). Also, the total mediating effect of total anxiety and depression and the total moderating effect of the number of alive children were significant on menopause symptoms. Conclusion: According to the results of the present study, there is an association between depression and menopausal symptoms. Therefore, health providers should pay more attention to the psychological health of women during the perimenopausal period. The predictor factors should be considered in both intervention and clinical assessment of menopause women.

Up to one-third of ischemic strokes remained cryptogenic despite extensive investigations. Atrial fibrillation may be detected in a significant proportion of patients with embolic stroke of undetermined source, particularly after the introduction of implantable loop recorder in clinical practice. We retrospectively included all the consecutive patients with embolic stroke of undetermined source referred to our units in the period November 2013 to December 2018 and in which an implantable loop recorder was positioned within 6 months from stroke event. Prevalence and predictors of atrial fibrillation were investigated. One hundred thirty-eight patients with embolic stroke of undetermined source fulfilling inclusion criteria were identified. The crude prevalence of atrial fibrillation at the end of observation period was of 45.7%. Incidence rates at 6, 12, 18, 24, and 36 months resulted, respectively, 31.8% (95% CI, 30.4–46.7), 38.0% (95% CI, 30.4–46.9), 42.6% (95% CI, 34.5–51.6), 46.6% (95% CI, 38.2–55.8), and 50.4% (95% CI, 41.6–59.9). On multivariate analysis, only excessive supraventricular electric activity and left atrial enlargement resulted to be significant predictors of atrial fibrillation (p = 0.037 and p

To conduct a scoping review to clarify the management of acromioclavicular joint osteoarthritis, as well as to identify any existing gaps in the current knowledge. Studies were identified by electronic databases (Ovid, Pubmed) from their inception up to April 2nd, 2020. All studies reporting functional outcomes after conservative or surgical treatment of acromioclavicular joint osteoarthritis, either primary or secondary to trauma or distal clavicle osteolysis, were included. Following data were extracted: authors, year of publication, study design (prospective or retrospective), LOE, number of shoulders treated conservatively or surgically, patients’ age, OA classification, type of conservative treatment, surgical approach, surgical technique, functional outcomes, complications, revisions, and length of follow-up. Descriptive statistics was used. Quality appraisal was assessed through the Cochrane risk of bias tool for LOE I/II studies, while the MINORS checklist was used for LOE III/IV studies. Nineteen studies were included for a total of 861 shoulders. Mean age of participants was 48.5 ± 7.4 years. Mean follow-up was 43.8 ± 29.9 months. Four studies reported functional results after conservative treatment, whereas 15 studies were focused on surgical management. No studies directly compared conservative and surgical treatment. Seven studies reported a surgical approach after failure of previous conservative treatment. All studies reported functional improvement and pain relief. Complication rate was low. Overall methodological quality of included studies was very low. Conservative and surgical treatments are both effective in acromioclavicular joint osteoarthritis management. However, available data did not allow to establish the superiority of one technique over another. Level IV.

The present study was performed to examine relationships between systemic exposure of capecitabine metabolites (5-FU, 5′-DFCR and 5′-DFUR) and toxicity or clinical response in patients with metastatic breast cancer. A population pharmacokinetic model for capecitabine and its three metabolites was built. Typical parameter values, characteristics of random distributions, associated with parameters, and covariates impact were estimated. Area under the curve (AUC) were computed for 5-FU and compared with grades of toxicity. Pharmacokinetic modeling was based on data collected on the first treatment cycle. Toxicity was assessed on the two first treatment cycles. The study was conducted in 43 patients. The population pharmacokinetic model (a one-compartment model per compound) was able to capture the very complex absorption process of capecitabine. Statistically significant covariates were cytidine deaminase, alkaline phosphatase and dihydrouracilemia (UH2)/uracilemia (U) ratio. UH2/U ratio was the most significant covariate on 5-FU elimination and CDA on the transformation of 5′-DFCR in 5′-DFUR. A trend was observed between 5-FU AUC and thrombopenia toxicity grades, but not with other toxicities. Best clinical response was not linked to systemic exposure of capecitabine metabolites. In our study, we propose a model able to describe, meanwhile, and its main metabolites, with a complex absorption process and inclusion of enzyme activity covariates such as CDA and UH2/U ratio. Trial registration Eudract 2008-004136-20, 2008/11/26

OBJECTIVESWe evaluated the long-term results of aortic root (AR) preservation and replacement in patients operated on for acute type A aortic dissection.METHODSOut of 302 patients discharged after repair of acute aortic dissection (1977–2019), 124 patients had an AR ≥40 mm, which was preserved in 84 (68%, group A) patients and replaced in 40 (32%, group B) patients. Group B patients were younger (mean age 57 ± 12 vs 62 ± 11 years, P = 0.07), with a mean AR of 47 vs 43 mm and ≥moderate aortic insufficiency in 65% vs 30%. Survival, causes of death and reoperations were analysed at mean follow-up of 9 ± 8 years (6 months to 40 years).RESULTSActuarial survival of discharged patients at 5, 10 and 15 years was 97% (0.89–0.99), 78% (0.67–0.90) and 75% (0.64–0.88) in group A, and 85% (0.71–0.95), 62% (0.44–0.78) and 57% (0.39–0.76) in group B (log-rank test P = 0.2). Nine patients in group A (7 patients for aortic insufficiency and dilatation of the root and 2 patients for pseudoaneurysm) and 1 patient of group B (pseudoaneurysm of the right coronary button) required proximal reoperation without deaths. At 5, 10 and 15 years, the cumulative incidence of proximal aortic reoperations was 5%, 9% and 25% in group A, and 0%, 3% and 3% in group B (P = 0.02). At multivariable analysis AR >45 mm [hazard ratio (HR) 6.8, P = 0.026] and age (HR 0.9, P = 0.016) were independently associated with proximal reoperation.CONCLUSIONSAR preservation in acute type A dissection showed acceptable long-term outcomes. Nevertheless, a more aggressive approach appears a valid option, especially in patients with AR diameter >45 mm.

Cord blood transplantation (CBT) is associated with low risk of leukemia relapse. Mechanisms underlying antileukemia benefit of CBT are not well understood, however a previous study strongly but indirectly implicated cells from the mother of the cord blood (CB) donor. A fetus acquires a small number of maternal cells referred to as maternal microchimerism (MMc) and MMc is sometimes detectable in CB. From a series of 95 patients who underwent double or single CBT at our center, we obtained or generated HLA-genotyping of CB mothers in 68. We employed a technique of highly sensitive HLA-specific quantitative-PCR assays targeting polymorphisms unique to the CB mother to assay CB-MMc in patients post-CBT. After additional exclusion criteria, CB-MMc was evaluated at multiple timepoints in 36 patients (529 specimens). CB-MMc was present in seven (19.4%) patients in bone marrow, peripheral blood, innate and adaptive immune cell subsets, and was detected up to 1-year post-CBT. Statistical trends to lower relapse, mortality, and treatment failure were observed for patients with vs. without CB-MMc post-CBT. Our study provides proof-of-concept that maternal cells of the CB graft can be tracked in recipients post-CBT, and underscore the importance of further investigating CB-MMc in sustained remission from leukemia following CBT.

Background Osteoarthritis (OA) is a chronic degenerative disease which can result in chronic pain, loss of joint function and consequently decline in quality of life. Research question A variety of instruments that measure the different dimensions of health status in patients with OA are available. However, despite the fact that WOMAC and other questionnaires and scales may provide additional understanding regarding the patient’s condition, some studies have reported discrepancies between patients’ perceptions and their actual ability to perform the task. The aim of the present study was investigate the physical capabilities with the function domain of WOMAC. Methods This study has a cross-sectional design including patients diagnosed with moderate to severe knee OA (i.e., grades II, III and IV) according to the Kellgren-Lawrence. These patients were submitted to the battery of functional tests recommended by the OARSI group (30-second chair stand test, 40 meters fast paced walking test, Stair climb test, timed “Up and Go”, and Six-minute walking test) and filled the WOMAC. Pearson’s correlation and multiple linear regression was applied. Results A total of 153 patients were included. A significant and weak correlation was observed between WOMAC and the 40-meter walking test, TUG, stair-climbing test, and the 6MWT. In addition, 30-second chair stand test demonstrated a significant and moderate correlation (r=-0.503). The multiple regression analysis results indicated that only 30-second chair stand test was a significant (p = 0.001) predictor of WOMAC. This result remains significant even after adjusting for age, BMI, total muscle mass, and number of knees affected Significance The 30-second chair stand test is associated with the WOMAC function domain. There is no correlation of this domain with any other functional tests, emphasizing the importance of including other tests for a global evaluation.

This study sought to determine the indications, characteristics, and outcomes of cardiovascular implantable electronic device (CIED) surgery in patients with LVAD.Many patients with a left ventricular assist device (LVAD) will require implantable cardioverter-defibrillator generator change or device revision or are candidates for de novo implantable cardioverter-defibrillator implantation following LVAD implantation.We performed an observational retrospective study of all LVAD recipients who subsequently underwent CIED surgery at Duke University Hospital from 2009 to 2019.A total of 159 patients underwent CIED surgery following LVAD implantation, including generator change (n = 93), device revision (n = 38), and de novo implant (n = 28). The median (interquartile range) time from LVAD implantation to CIED surgery was 18.1 months (5.5 to 35.1 months). Pre-operative risk for infection was elevated in the overall cohort with a median (interquartile range) Prevention of Arrhythmia Device Infection Trial (PADIT) score of 7.0 (5.0 to 9.0). Pocket hematoma occurred in 21 patients (13.2%) following CIED surgery. Antimicrobial envelops were used in 43 patients (27%). Device infection due to CIED surgery occurred in 5 (3.1%) patients and occurred only in patients who developed post-operative pocket hematoma (p 0.001). Mortality at 1 year following CIED surgery was 20% (n = 32).CIED surgery following LVAD implantation is associated with an increased risk for pocket hematoma and CIED infection. Further studies are needed to determine the risk-benefit ratio of CIED surgery in patients with LVADs.

OptiVol (Medtronic PLC, Minneapolis, MN) is a diagnostic feature of some cardiac implantable electronic devices (CIEDs) based on changes in thoracic impedance (TI) over time. Changes in TI can predict heart failure (HF) hospitalizations and mortality in HF populations. However, the utility of this feature is unknown in patients with a left ventricular assist device (LVAD). To determine if OptiVol and TI correlate with clinical HF events in a population of LVAD patients, hospitalization outcomes were collected retrospectively from the electronic health records at a single academic medical center in 80 LVAD patients with an OptiVol-capable CIED. Demographics, medical history, and available clinical data were reviewed and reported. The primary outcomes of interest were TI and OptiVol trends before and after hospitalization, and association of trends before and after these events was evaluated. Most patients had a HeartMate II LVAD and most CIEDs were defibrillators, and 23 (29%) had at least one HF hospitalization during the study period. HF hospitalizations were preceded by signs of volume overload in Optivol (60%) and TI (78%) with recovery of these measures post hospitalization in 33% and 25% of patients, respectively. Monitoring of TI and OptiVol may be one effective component of HF management in LVAD patients as part of a comprehensive program.

Although the use of treosulfan (TREO) in conventional donor hematopoietic cell transplantation (HCT) has been extensively evaluated, its use in cord blood transplantation (CBT) for hematologic malignancies has not been reported. Between March 2009 and October 2019, 130 CBT recipients were enrolled in this prospective multicenter phase 2 study. The conditioning regimen consisted of TREO, fludarabine, and a single fraction of 2 Gy total-body irradiation. Cyclosporine and mycophenolate mofetil were used for graft-versus-host disease prophylaxis. The primary end point was incidence of graft failure (GF), and based on risk of GF, patients were classified as low risk (arm 1, n = 66) and high risk (arm 2, n = 64). The median age was 45 years (range, 0.6-65 years). Disease status included acute leukemias in first complete remission (CR; n = 56), in ≥2 CRs (n = 46), and myelodysplastic (n = 25) and myeloproliferative syndromes (n = 3). Thirty-five patients (27%) had received a prior HCT. One hundred twenty-three patients (95%) engrafted, with neutrophil recovery occurring at a median of 19 days for patients on arm 1 and 20 days for patients on arm 2. The 3-year overall survival, relapse-free survival (RFS), transplant-related mortality, and relapse for the combined groups were 66%, 57%, 18%, and 24%, respectively. Among patients who had a prior HCT, RFS at 3 years was 48%. No significant differences in clinical outcomes were seen between the 2 arms. Our results demonstrate that TREO-based conditioning for CBT recipients is safe and effective in promoting CB engraftment with favorable clinical outcomes. This trial was registered at www.clinicaltrials.gov as #NCT00796068.

Background An early report of recipient heart transplantation outcomes under the new U.S. heart allocation system introduced in late 2018 found a lower post-transplant survival rate compared with that of the prior system. Objectives The aim of this study was to examine recipient survival under the new system by using an updated dataset. Methods The 2015 to 2019 United Network for Organ Sharing registry was queried for adult heart transplant recipients, stratified according to whether the subjects were listed and underwent transplant before or after October 18, 2018, when the new allocation system was implemented. The association between allocation system and recipient mortality was analyzed by using the Kaplan-Meier method and multivariable Cox proportional hazards regression. Results A total of 7,119 recipients met inclusion criteria: 6,004 (84%) and 1,115 (16%) listed and undergoing transplant in the old and new allocation systems, respectively. This registry update included 576 new-system recipients, more than double the amount previously analyzed. Recipients from the new system were more likely to be bridged to transplant with temporary mechanical circulatory support devices instead of durable left ventricular assist devices and had longer graft ischemic times. After adjustment, the new system was not associated with poorer survival on Kaplan-Meier survival analysis (log-rank test; p = 0.075) or multivariable Cox proportional hazards modeling (adjusted hazard ratio: 1.18; 95% confidence interval: 0.90 to 1.55). Conclusions The short-term survival of recipients listed and receiving a transplant under the old and new allocation systems seems to be comparable. The modification to the allocation system has resulted in several changes to the clinical profiles of patients undergoing transplants that must be closely monitored in the coming years.

Purpose The “Spedali Civili”, one of the largest hospitals in the Italian region most affected by SARS-CoV-2 infection, is managing a large number of traumatic injuries. The objective of this article is to share our operational protocols to deliver an appropriate hospital trauma care in the context of the COVID-19 pandemic. Methods We changed our work shifts, in consideration of the high number of patients; colleagues from smaller hospitals in the area joined us to increase the number of surgeons available. Thanks to the collaboration between orthopaedists, anaesthesiologists, and nurses, we created a flow chart and separate routes (in the emergency room, in the wards, and in the operating rooms) to optimize patient management. Our protocols allow us to always provide healthcare professionals with the correct personal protective equipment for the task they are performing. Results Our strategies proved to be practical and feasible. Having a well thought plan helped us to provide for the most robust response possible. We have not yet been able to study the effectiveness of our protocols, and our recommendations may not be applicable to all healthcare facilities. Nonetheless, sharing our early experience can help other institutions conducting and adapting such plans more quickly. Conclusions Having a clear strategy during the COVID-19 pandemic kept our systems resilient and effective and allowed us to provide high-quality trauma care. We offer this approach for other institutions to adopt and adapt to their local setting.

BACKGROUND: Obesity is associated with numerous comorbidities and affects various aspects of life, including quality of life (QOL) and sexual function (SF). Bariatric surgery (BS) is an effective treatment for obese people. Also QOL and SF after BS in the people are not well known. AIMS: To provide insight in the available prospective evidence regarding the short and long-term effects of BS on QOL and SF. MATERIALS AND METHODS: A systematic multi-database search was conducted for ‘quality of life’, ‘Sexual function’ and ‘Bariatric surgery’. Only prospective studies with QOL or SF before and after BS were included. The ‘quality assessment tool for before–after studies with no control group’ was used to assess the methodological quality. RESULTS: Twenty-four studies met the inclusion criteria. Most studies were assessed to be of ‘fair’ to ‘good’ methodological quality. Seven different questionnaires were used to measure both QOL and SF. A significant increase in QOL after BS and light increase in SF were found in all studies (P≤0.05). CONCLUSIONS: Both QOL and SF are increased after BS on both the short and long term. However, due to the heterogeneity of the studies and the generality of the questionnaires are them hard to make a distinction among different BS and difficult to see a relation with medical profit. Therefore, designing QOL and SF measurements to the post BS population are recommended as the focus of future studies.

Objectives The goal of this study was to assess the utility of transvenous lead extraction for cardiovascular implantable electronic device (CIED) infection in patients with a left ventricular assist device (LVAD). Background The utility of transvenous lead extraction for the management CIED infection in patients with a durable LVAD has not been well described. Methods Clinical and outcomes data were collected retrospectively among patients who underwent lead extraction for CIED infection after LVAD implantation at Duke University Hospital. Results Overall, 27 patients (n = 6 HVAD; n = 15 HeartMate II; n = 6 Heartmate III) underwent lead extraction for infection. Median (interquartile range) time from LVAD implantation to infection was 6.1 (2.5, 14.9) months. Indications included endocarditis (n = 16), bacteremia (n = 9), and pocket infection (n = 2). Common pathogens were Staphylococcus aureus (n = 10), coagulase-negative staphylococci (n = 7), and Enterococcus faecalis (n = 3). Sixty-eight leads were removed, with a median lead implant time of 5.7 (3.6, 9.2) years. Laser sheaths were used in all procedures, with a median laser time of 35.0 (17.5, 85.5) s. Mechanical cutting tools were required in 11 (40.7%) and femoral snaring in 4 (14.8%). Complete procedural success was achieved in 25 (93.6%) patients and clinical success in 27 (100%). No procedural failures or major adverse events occurred. Twenty-one patients (77.8%) were alive without persistent endovascular infection 1 year after lead extraction. Most were treated with oral suppressive antibiotics after extraction (n = 23 [82.5%]). Persistent infection after extraction occurred in 4 patients and was associated with 50% 1-year mortality. Conclusions Transvenous lead extraction for LVAD-associated CIED infection can be performed safely with low rates of persistent infection and 1-year mortality.

Background:: Gender dysphoria is a clinical condition in which a state of inner suffering, stress and anxiety is detected when biological sex and a person's gender identity do not coincide. People who identify themselves as transgender people are more vulnerable and may have higher rates of dissatisfaction with their bodies which are often associated with a disorderly diet in an attempt to change the bodily characteristics of the genus of birth and, conversely, to accentuate the characteristics of the desired sexual identity. Aim:: The purpose of this work is to examine the association between dissatisfaction with one's own body and eating and weight disorders in people with gender dysphoria. Results:: Gender dysphoria and eating disorders are characterized by a serious discomfort to the body and the body suffers in both conditions. The results of our study suggest that rates of pathological eating behaviors and symptoms related to a disordered diet are high in patients with gender dysphoria and that standard screening for these symptoms must be considered in both populations at the time of evaluation and during the course of the treatment. Conclusions:: In light of this evidence, clinicians should always investigate issues related to sexuality and gender identity in patients with eating disorders, to develop more effective prevention measures and better strategies for therapeutic intervention..

Acute kidney injury (AKI) and primary graft dysfunction (PGD) are serious complications after heart transplantation (HT). The relationship between AKI and PGD is poorly understood. We sought to examine the incidence of AKI and identify risk factors associated with AKI. We hypothesized that PGD is one of the risk factors independently associated with post-HT AKI. We gathered data for all adult patients who underwent HT between 2009 and 2014. AKI was defined by the KDIGO criteria. PGD was categorized using ISHLT criteria. We assessed univariable and multivariable logistic regression to identify risk factors independently associated with post-HT AKI. Out of 316 patients, postoperative AKI occurred in 273 (86%) patients: 188 (68%) stage I, 44 (16%) stage II, and 41 (15%) stage III. Stage II/III AKI was associated with increased risk of mortality at 1 year. There was significant association between severe PGD and stage II/III AKI (P = 0.001, OR 3.63, 95% CI: 1.69-7.94). Other clinical factors significantly associated with stage II/III AKI included longer donor brain death duration and lower recipient baseline creatinine. We found that stage II/III AKI is common and independently associated with severe PGD. Another potentially modifiable risk factor is donor brain death duration.

Retrospective studies have shown an increased risk of second primary lung cancer in patients with a history of head and neck cancer (HNC). No population-based study has examined the overall survival (OS) outcomes of patients with second primary non-small-cell lung cancer (NSCLC) after HNC comparison with patients with first primary NSCLC.Individuals with histologically confirmed NSCLC diagnosed after nonmetastatic squamous-cell carcinoma of the head and neck (HNC-NSCLC; n = 3597) were identified in Surveillance, Epidemiology, and End Results 18 registries (1988-2013). OS and baseline characteristics were compared in patients with first primary NSCLC (NSCLC-1; n = 365,551) in the same registries.Squamous NSCLC was more common in HNC-NSCLC (n = 745 [64.1%] localized, n = 833 [71.9%] regional, and n = 811 [63.5%] distant) than in the NSCLC-1 (n = 30,901 [38.3%] localized, n = 50,557 [48.2%] regional, and n = 53,720 [29.8%] distant; P .001). The leading cause of death in HNC-NSCLC was NSCLC (n = 2183; 60.6%), and median OS after localized, regional, and distant NSCLC diagnosis was 2.50 years, 1.17 years, and 5 months, respectively. For NSCLC-1, median OS was 4.58 years, 1.58 years, and 6 months, respectively. These differences were significant (P .001). In multivariable analysis, a history of HNC remained associated with worse OS for localized (hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.29-1.51; P .001), regional (HR, 1.26; 95% CI, 1.19-1.35; P .001) and distant (HR, 1.11; 95% CI, 1.04-1.18; P .01) stage NSCLC.A history of HNC adversely affects OS in patients who subsequently develop NSCLC. This OS decrement might have implications for NSCLC surveillance and NSCLC therapy selection in this population.

Introduction Lead dysfunction can lead to serious consequences including failure to treat ventricular tachycardia or fibrillation (VT/VF). The incidence and mechanisms of lead dysfunction following left ventricular assist device (LVAD) implantation are not well-described. We sought to determine the incidence, mechanisms, timing, and complications of right ventricular lead dysfunction requiring revision following LVAD implantation. Methods Retrospective observational chart review of all LVAD recipients with pre-existing implantable cardioverter-defibrillator (ICD) from 2009 to 2018 was performed including device interrogation reports, laboratory and imaging data, procedural reports, and clinical outcomes. Results Among 583 patients with an ICD in situ undergoing LVAD implant, the median (interquartile range) age was 62.5 (15.7) years, 21% were female, and the types of LVADs included HeartWare HVAD (26%), HeartMate II (52%), and HeartMate III (22%). Right ventricular lead revision was performed in 38 patients (6.5%) at a median (25th, 75th) of 16.4 (3.6, 29.2) months following LVAD. Mechanisms of lead dysfunction included macrodislodgement (n = 4), surgical lead injury (n = 4), recall (n = 3), insulation failure (n = 8) or conductor fracture (n = 7), and alterations in the lead-myocardial interface (n = 12). Undersensing requiring revision occurred in 22 (58%) cases. Clinical sequelae of undersensing included failure to detect VT/VF (n = 4) and pacing-induced torsade de pointes (n = 1). Oversensing occurred in 12 (32%) and sequelae included inappropriate antitachycardia pacing ([ATP], n = 8), inappropriate ICD shock (n = 6), and ATP-induced VT (n = 1). Conclusion The incidence of right ventricular lead dysfunction following LVAD implantation is significant and has important clinical sequelae. Physicians should remain vigilant for lead dysfunction after LVAD surgery and test lead function before discharge.