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OBJECTIVE External ventricular drainage (EVD) catheters are associated with complications such as EVD catheter infection (ECI), intracranial hemorrhage (ICH), and suboptimal placement. The aim of this study was to investigate the rates of EVD catheter complications and their associated risk factor profiles in order to optimize the safety and accuracy of catheter insertion. METHODS A total of 348 patients with urgently placed EVD catheters were included as a part of a prospective multicenter observational cohort. Strict definitions were applied for each complication category. RESULTS The rates of misplacement, ECI/ventriculitis, and ICH were 38.6%, 12.2%, and 9.2%, respectively. Catheter misplacement was associated with midline shift (p = 0.002), operator experience (p = 0.031), and intracranial length (p < 0.001). Although mostly asymptomatic, ICH occurred more often in patients receiving prophylactic low-molecular-weight heparin (LMWH) (p = 0.002) and those who required catheter replacement (p = 0.026). Infectious complications (ECI/ventriculitis and suspected ECI) occurred more commonly in patients whose catheters were inserted at the bedside (p = 0.004) and those with smaller incisions (≤ 1 cm) (p < 0.001). ECI/ventriculitis was not associated with preinsertion antibiotic prophylaxis (p = 0.421), catheter replacement (p = 0.118), and catheter tunneling length (p = 0.782). CONCLUSIONS EVD-associated complications are common. These results suggest that the operating room setting can help reduce the risk of infection, but not the use of preoperative antibiotic prophylaxis. Although EVD-related ICH was associated with LMWH prophylaxis for deep vein thrombosis, there were no significant clinical manifestations in the majority of patients. Catheter misplacement was associated with operator level of training and midline shift. Information from this multicenter prospective cohort can be utilized to increase the safety profile of this common neurosurgical procedure.

Objectives Minimally invasive flap designs have been introduced to enhance blood clot stability and support wound healing. Limited data appear to suggest, that in intrabony defects, better clinical outcomes can be achieved by means of minimally invasive flap compared to more extended flaps. The aim of this study was to evaluate the healing of intrabony defects treated with either minimally invasive surgical flaps or with modified or simplified papilla preservation techniques in conjunction with the application of an enamel matrix derivative (EMD). Materials and methods Forty-seven subjects were randomly assigned to either test (N = 23) or control (N = 24) procedures. In the test group, the intrabony defects were accessed by means of either minimally invasive surgical technique (MIST) or modified minimally invasive surgical technique (M-MIST) according to the defect localization while the defects in the control group were treated with either the modified or simplified papilla preservation (MPP) or the simplified papilla preservation technique (SPP). EMD was used as regenerative material in all defects. The following clinical parameters were recorded at baseline and after 12 months: full-mouth plaque score (FMPS), full-mouth bleeding score (FMBS), probing depths (PD), clinical attachment level (CAL), and gingival recession (GR). Early healing index (EHI) score was assessed in both groups 1 week following the surgery. CAL gain was set as primary outcome. Results After 12 months follow-up, the CAL gain was 4.09 ± 1.68 mm in test group and 3.79 ± 1.67 mm in control group, while the PD reduction was 4.52 ± 1.34 mm and 4.04 ± 1.62 mm for test and control sites. In both groups, a minimal GR increase (0.35 ± 1.11 mm and 0.25 ± 1.03 mm) was noted. No residual PDs ≥ 6 mm were recorded in both groups. CAL gains of 4–5 mm were achieved in 30.4% and in 29.2% of test and control group, respectively. Moreover, CAL gains ≥ 6 mm were recorded in 21.7% of experimental sites and in 20.8% of control sites. No statistically significant differences in any of the evaluated parameters were found between the test and control procedures (P > 0.05). After 1 week post-surgery, a statistically significant difference (P Conclusions Within the limits of this pilot RCT, the results have failed to show any differences in the measured parameters following treatment of intrabony defects with EMD, irrespective of the employed surgical technique. Clinical relevance In intrabony defects, the application of EMD in conjunction with either MIST/M-MIST or M-PPT/SPPT resulted in substantial clinical improvements.

PurposeBinding proteins (G-proteins) mediate signalling pathways involved in diverse cellular functions and comprise Gα and Gβγ units. Human diseases have been reported for all five Gβ proteins. A de novo missense variant in GNB2 was recently reported in one individual with developmental delay/intellectual disability (DD/ID) and dysmorphism. We aim to confirm GNB2 as a neurodevelopmental disease gene, and elucidate the GNB2-associated neurodevelopmental phenotype in a patient cohort.MethodsWe discovered a GNB2 variant in the index case via exome sequencing and sought individuals with GNB2 variants via international data-sharing initiatives. In silico modelling of the variants was assessed, along with multiple lines of evidence in keeping with American College of Medical Genetics and Genomics guidelines for interpretation of sequence variants.ResultsWe identified 12 unrelated individuals with five de novo missense variants in GNB2, four of which are recurrent: p.(Ala73Thr), p.(Gly77Arg), p.(Lys89Glu) and p.(Lys89Thr). All individuals have DD/ID with variable dysmorphism and extraneurologic features. The variants are located at the universally conserved shared interface with the Gα subunit, which modelling suggests weaken this interaction.ConclusionMissense variants in GNB2 cause a congenital neurodevelopmental disorder with variable syndromic features, broadening the spectrum of multisystem phenotypes associated with variants in genes encoding G-proteins.

Introduction In the present study, we have reviewed the outcomes of patients with supracricoid partial laryngectomy (SCPL) in our institution. Our results show that SCPL is a well-tolerated procedure with generally good functional outcomes for patients with advanced laryngeal cancer. Objective We analyzed the oncological and functional results of a cohort of 35 patients who had undergone SCPL, and we highlighted the complications, identified the overall and disease-free survivals, demonstrating that the reconstructive laryngectomy guarantees the oncological safety and reproducibility of the oncological results, preserving the laryngeal functions and promoting an improvement in the patient's quality of life, favoring communication and interpersonal relationships. Methods Between 2010 and 2018, 35 patients underwent SCPL for primary and recurrent laryngeal squamous cell carcinomas, and they were divided into two subgroups: in 16 cases, the cricohyoidoepiglottopexy according to the Mayer-Piquet technique was performed, while the remaining 19 cases were submitted to the cricohyoidopexy according to the Labayle technique. In addition to evaluating the oncological results of patients undergoing reconstructive laryngectomy, the present study also aimed to evaluate the functionality of the residual larynx and the quality of life. Results The overall and disease-free survivals were of 83% and 76.3% respectively. All patients were able to swallow. The nasogastric tube was removed after a mean period of 21.8 days (range: 14 to 28 days). The mean decannulation time was of 23.4 days after surgery (range: 15 to 36 days). Conclusion The curves for the overall and disease-free survivals show that SCPL can guarantee oncological safety comparable to that of total laryngectomies in diseases in the intermediate stage and in carefully-selected advanced stages.

Alagille syndrome (ALGS) is a multisystemic disease caused by mutations in genes of Notch pathway, which regulates embryonic cell differentiation and angiogenesis. Clinically, ALGS is characterized by cholestasis, cardiac defects, characteristic facial features, skeletal and ophthalmologic abnormalities. The aim of this review is to illustrate neuroradiological findings in ALGS, which are less well-known and prevalent, including cerebrovascular anomalies (such as aneurysms, dolichoectasia, Moyamoya syndrome and venous peculiarities), Chiari 1 malformation, craniosynostosis, intracranial hypertension, and vertebral anomalies (namely butterfly vertebra, hemivertebra, and craniocervical junction anomalies). Rarer cerebral midline malformations and temporal bone anomalies have also been described.

Introduction: Intramedullary locking devices (ILDs) have recently been advocated as a minimally invasive approach to manage displaced intraarticular calcaneal fractures (DIACFs), to minimise complications and improve outcomes. We reviewed clinical and biomechanical studies dealing with commercially available devices to identify their characteristics, efficacy and safety. Methods: Following a PRISMA checklist, Medline, Scopus and EMBASE databases were searched to identify studies reporting the use of ILDs for treating DIACFs. Biomechanical studies were first evaluated. Cohort studies were then reviewed for demographics, surgical technique, postoperative protocol, clinical and radiographic scores, complications and reoperations. The modified Coleman Methodology Score (CMS) was used to assess the quality of studies. Results: Eleven studies were identified which investigated two devices (Calcanail®, C-Nail®). Three biomechanical studies proved they offered adequate primary stability, stiffness, interfragmentary motion and load to failure. Eight clinical studies (321 feet, 308 patients) demonstrated a positive clinical and radiographic outcome at 16-months average follow-up. Metalware irritation (up to 20%) and temporary nerve entrapment symptoms (up to 30%) were the most common complications, while soft tissue issues (wound necrosis, delayed healing, infection) were reported in 3–5% of cases. Conversion to subtalar fusion was necessary in up to 6% of cases. Four (50%) out of 8 studies were authored by implant designers and in 5 (62%) relevant conflicts of interest were disclosed. Mean (± standard deviation) CMS was 59 ± 9.8, indicating moderate quality. Conclusions: Treating DIAFCs with ILDs leads to satisfactory clinical outcomes at short-term follow-up, enabling restoration of calcaneal height and improved subtalar joint congruency. Metalware irritation and temporary nerve entrapment symptoms are common complications although wound complications are less frequent than after open lateral approaches. The quality of evidence provided so far is moderate and potentially biased by the conflict of interest, raising concerns about the generalisability of results. Level of evidence: Level V – Review of Level III to V studies.

Background Various prediction models have been developed to predict the risk of kidney failure in patients with CKD. However, guideline-recommended models have yet to be compared head to head, their validation in patients with advanced CKD is lacking, and most do not account for competing risks. Methods To externally validate 11 existing models of kidney failure, taking the competing risk of death into account, we included patients with advanced CKD from two large cohorts: the European Quality Study (EQUAL), an ongoing European prospective, multicenter cohort study of older patients with advanced CKD, and the Swedish Renal Registry (SRR), an ongoing registry of nephrology-referred patients with CKD in Sweden. The outcome of the models was kidney failure (defined as RRT-treated ESKD). We assessed model performance with discrimination and calibration. Results The study included 1580 patients from EQUAL and 13,489 patients from SRR. The average c statistic over the 11 validated models was 0.74 in EQUAL and 0.80 in SRR, compared with 0.89 in previous validations. Most models with longer prediction horizons overestimated the risk of kidney failure considerably. The 5-year Kidney Failure Risk Equation (KFRE) overpredicted risk by 10%-\18%. The four- and eight-variable 2-year KFRE and the 4-year Grams model showed excellent calibration and good discrimination in both cohorts. Conclusions Some existing models can accurately predict kidney failure in patients with advanced CKD. KFRE performed well for a shorter time frame (2 years), despite not accounting for competing events. Models predicting over a longer time frame (5 years) overestimated risk because of the competing risk of death. The Grams model, which accounts for the latter, is suitable for longer-term predictions (4 years).

Cervical Dystonia (CD) and Parkinson's disease, particularly tremor-dominant motor phenotype (TD-PD), showed a selective deficit of time-based prospective memory (TBPM). The two movement disorders are mainly characterized by dysfunctions of basal-ganglia and prefrontal cortex but it is reported that cerebellum also plays a key role in their pathogenesis. These cerebral structures are specifically involved in TBPM rather than in event-based PM (EBPM), but until now no study directly compared these two components of PM between CD and TD-PD patients. Therefore, the present study aimed at investigating if differences in PM functioning between CD and TD-PD patients might exist and if the type of movement disorder moderated the relationship between deficit of PM and deficit of executive functions and retrospective memory. Thirty TD-PD, 27CD patients and 29 healthy subjects (HCs), matched for demographic features, underwent neuropsychological tests for PM, executive functions, retrospective memory and self-rated questionnaires. The three groups did not differ on neuropsychological variables except for TBPM where TD-PD and CD patients performed worse than HCs; moreover, TD-PD performed worse than CD patients. Moderation analysis indicated that the type of movement disorder moderated the relationship between executive dysfunction and TBPM, but not EBPM. In conclusion, selective deficit of TBPM characterizes both CD and TD-PD but it is associated with executive dysfunction only in TD-PD. It might be possible to speculate that the involvement of the cerebellum, responsible for internal timing processes, could explain the impairment of TBPM in both movement disorders. This issue deserves to be explored in future neuroimaging studies.

Background The mechanical disruption and removal of the subgingival biofilm represent the most important step in the treatment of periodontitis. However, in deep periodontal pockets, mechanical removal of the subgingival biofilm is difficult and frequently incomplete. Preliminary findings indicate that the use of amino acid buffered sodium hypochlorite (NaOCl) gel may chemically destroy the bacterial biofilm and facilitate its mechanical removal. Objectives To clinically evaluate the efficacy of minimally invasive nonsurgical therapy (MINST) of periodontal pockets with or without local application of an amino acid buffered sodium hypochlorite (NaOCl) gel. Materials and methods Forty untreated patients diagnosed with severe/advanced periodontitis (i.e. stage III/IV) with a slow/moderate rate of progression (i.e. grade A/B) were randomly allocated in two treatment groups. In the test group, the periodontal pockets were treated by means of MINST and NaOCl gel application, while in the control group, treatment consisted of MINST alone. Full-mouth plaque scores (FMPS), full-mouth bleeding scores (FMBS), probing depths (PD), clinical attachment levels (CAL) and gingival recessions (GR) were assessed at baseline and at 6 months following therapy. The primary outcome variable was PD reduction at sites with PD ≥ 5 mm at baseline. Results At 6 months, statistically significant differences between the two groups were found (p = 0.001) in terms of PD and CAL change. No statistically significant differences were found in terms of GR (p = 0.81). The number of sites with PD ≥ 5 mm and BOP (+) decreased statistically significantly (p = 0.001), i.e. from 85.3 to 2.2% in the test group and from 81.6 to 7.3% in the control group, respectively. Statistically significant differences between test and control groups were recorded at 6 months (p = 0.001). MINST + NaOCl compared to MINST alone decreased statistically significantly (p = 0.001) the probability of residual PDs ≥ 5 mm with BOP− (14.5% vs 18.3%) and BOP+ (2.2% vs. 7.2%). Conclusions Within their limits, the present results indicate that (a) the use of MINST may represent a clinically valuable approach for nonsurgical therapy and (b) the application of NaOCl gel in conjunction with MINST may additionally improve the clinical outcomes compared to the use of MINST alone. Clinical relevance In patients with untreated periodontitis, treatment of deep pockets by means of MINST in conjunction with a NaOCl gel may represent a valuable approach to additionally improve the clinical outcomes obtained with MINST alone

The growing use of imaging examinations has led to increased detection of spontaneous coronary artery dissection (SCAD) as a non-atherosclerotic cause of acute coronary syndrome (ACS). Since a greater awareness of pathophysiologic mechanisms has relevant implications in clinical practice, we aim to provide an update to current knowledge of SCAD pathophysiology. We discuss the most common conditions associated with SCAD, including predisposing factors and triggers, and focus on potential mechanisms leading to SCAD development. Furthermore, we report the main genetic research findings that have shed further light on SCAD pathophysiology. Finally, we summarize practical considerations in SCAD management based on pathophysiologic insights.

Neonatal and infantile cholestasis (NIC) can represent the onset of a surgically correctable disease and of a genetic or metabolic disorder worthy of medical treatment. Timely recognition of NIC and identification of the underlying etiology are paramount to improve outcomes. Upon invitation by the Italian National Institute of Health (ISS), an expert working grouped was formed to formulate evidence-based positions on current knowledge about the diagnosis of NIC. A systematic literature search was conducted to collect evidence about epidemiology, etiology, clinical aspects and accuracy of available diagnostic tests in NIC. Evidence was scored using the GRADE system. All recommendations were approved by a panel of experts upon agreement of at least 75% of the members. The final document was approved by all the panel components. This position document summarizes the collected statements and defines the best-evidence diagnostic approach to cholestasis in the first year of life.

Background Yolk sac tumor (YST) is a malignant entity that often occurs in girls less than 3 years of age and is the most frequent type of primary extragonadal germ cell tumor. Case We describe the case of an 11-month-old girl who was referred to our center for vaginal bleeding with evidence of a uterine mass on ultrasonography. Preoperative investigations confirmed YST of the uterine cervix without metastasis. After 4 cycles of systemic chemotherapy, the patient was treated with laparoscopic trachelectomy (fertility-sparing surgery) without perioperative complications. Summary and Conclusion After 12 months of follow-up, no residual mass was seen. The laparoscopic technique for trachelectomy for uterine cervix YST seems to be feasible and safe in children under 1 year of age.

To comparatively assess the role of abdominal ultrasound (US) and magnetic resonance imaging (MRI) in predicting long-term medical outcome in native liver survivor patients with biliary atresia (BA) after Kasai portoenterostomy (KP). Twenty-four retrospectively enrolled patients were divided in two groups according to clinical and laboratory data at initial evaluation after KP (median follow-up = 9.7 years; range = 5–25 years) as with ideal (Group 1; n = 15) or non-ideal (Group 2; n = 9) medical outcome. All patients were re-evaluated for a period of additional 4 years using clinical and laboratory indices. US and MRI studies were qualitatively analyzed assessing imaging signs suggestive of chronic liver disease (CLD). At re-evaluation, 6 patients (40%) of Group 1 changed their medical outcome in non-ideal (Group 1A); the other 9 patients (60%) remained stable (Group 1B); the mean time to change the medical outcome in non-ideal status at re-evaluation was 43.5 ± 2.3 months. The area under the ROC curve was 0.84 and 0.87 for US and MRI scores to predict long-term medical outcome with the best cut-off value score > 4 for both modalities (p = 0.89). In Group 2, 6 (67%) patients showed a clinical progression (Group 2A) with a mean time of 39.8 ± 3.8 months; in the other 3 (33%) patients, no clinical progression was observed (Group 2B). In BA patients with ideal medical outcome after KP, US and MRI may both predict long-term outcome. US, non-invasive and widely available technique, should be preferred.

Background and aim: Neurodegeneration with brain iron accumulation (NBIA) and Wilson’s disease (WD) is considered the prototype of neurodegenerative disorders characterised by the overloading of iron and copper in the central nervous system. Growing evidence has unveiled the involvement of these metals in brain cortical neurotransmission. Aim of this study was to assess cortical excitability profile due to copper and iron overload. Methods: Three patients affected by NBIA, namely two patients with a recessive hereditary parkinsonism (PARK9) and one patient with aceruloplasminemia and 7 patients with neurological WD underwent transcranial magnetic stimulation (TMS) protocols to assess cortical excitability. Specifically, we evaluated the motor thresholds that reflect membrane excitability related to the voltage-gated sodium channels in the neurons of the motor system and the ease of activation of motor cortex via glutamatergic networks, and ad hoc TMS protocols to probe inhibitory-GABAergic (short interval intracortical inhibition, SICI; short-latency afferent inhibition, SAI; cortical silent period, CSP) and excitatory intracortical circuitry (intracortical facilitation, ICF). Results: Patients with NBIA exhibited an abnormal prolongation of CSP respect to HC and WD patients. On the contrary, neurological WD displayed higher motor thresholds and reduced CSP and SICI. Conclusion: Hereditary conditions due to overload of copper and iron exhibited peculiar cortical excitability profiles that can help during differential diagnosis between these conditions. Moreover, such results can give us more clues about the role of metals in acquired neurodegenerative disorders, such as Parkinson disease, Alzheimer disease, and multiple sclerosis.

Introduction Executive dysfunctions are observed in focal dystonia (i.e., blepharospasm and cervical dystonia). Prospective memory (PM) is the ability to remember to carry out intended actions in the future and plays a relevant role in everyday living and quality of life. Although alterations of prefrontal cortex occur in focal dystonia, until now, no study has yet investigated the occurrence of deficit of PM in focal dystonia. Therefore, the aim of the study was to explore PM and its cognitive correlates in cervical dystonia and blepharospasm. Methods Twenty-seven patients with blepharospasm, 26 patients with cervical dystonia and 30 healthy subjects, matched for demographic features, underwent neuropsychological tests assessing PM, verbal memory, executive functions, and questionnaires assessing subjective prospective and retrospective memory failures, and apathy. Results The three groups did not differ on tests assessing verbal memory, executive functions, but they significantly differed on PM tests. In detail, patients with blepharospasm and cervical dystonia performed worse on time-based and recognition tasks than healthy subjects, while no difference on event-based task was found. Regression analysis showed a relationship between a lower score on Modified Card Sorting Test and a reduced performance on time-based, event-based and recognition tasks within focal dystonia group. Conclusion The results indicated a selective deficit of time-based PM in focal dystonia, supporting previous evidence of cognitive dysfunctions in dystonic patients. The relationship between impaired time-based PM and poor performance on cognitive flexibility tests might suggest that difficulty in managing two concurrent cognitive demands contributes to impaired time-based PM.

Introduction: The management of squamous cell carcinoma (SCC) of the tongue represents the most demanding treatment planning in head and neck surgery. Ablation followed by free flap reconstruction is considered the gold standard, but not all patients are suitable for this strategy. The aim of this review is to provide a comprehensive view of surgical reconstruction possibilities in patients not eligible for free flaps. Methods: Following PRISMA recommendations, a systematic literature review was conducted searching for original papers that investigated outcomes of patients treated by surgical ablation for tongue SCC followed by reconstruction with local or pedicled flaps. Selected papers were read and data extracted for qualitative analysis. Results: Twenty articles met the inclusion/exclusion criteria. The study design was case series in sixteen papers, cohort study in the remaining four. Four different local flaps (BMM, FAMM, NLIF, SMIF) and four regional flaps have been discussed in included studies (IHF, SFIF, SCM, PMMC). Conclusion: The improved anatomical knowledge makes local flaps a reliable alternative to free tissue transfer in cases requiring small-/medium-sized defects. Regional flaps still represent cornerstones in reconstruction of the tongue. Ease of execution, costs-to-benefit ratio, low-rate complications, minimal donor site morbidity represent the best advantages choosing local/regional flaps.

Heart failure (HF) with preserved left ventricular (LV) ejection fraction (HFpEF) represent today the largest ‘unmet medical need’, because none of the drugs presently available improved survival in this consistent proportion of patients with HF, ∼50% of the total, who have an LV ejection fraction ≥50%. Heart failure with preserved left ventricular ejection fraction is a clinical syndrome that in its classical form, is associated to typical risk factors and comorbidities. The comorbidities represent one of the element contributing to the extreme heterogeneity which characterizes HFpEF. The pathophysiological mechanisms, as well as the clinical presentation, are multifaceted. These factors explain, by and large, the failure of a generalized therapeutic strategy, while build the argument for personalized medicine, designed to address the specific phenotypes, with therapies proven in specific subgroups of patients with HFpEF to reduce mortality and improve ‘surrogate’ outcomes, such as quality of life.

OBJECTIVES: Sofosbuvir/Ledipasvir (SOF/LDV) has been approved by the European Medicine Agency (EMA) for the treatment of children and adolescents (at least 3 years of age) with chronic hepatitis C (CHC) genotype 1, 3, and 4 infection. The aim of this study was to evaluate the efficacy and safety of SOF/LDV in adolescents (12 to

Myositis ossificans traumatica (MOT) is a self-limiting and self-resolving pathology. In most cases, conservative treatment is chosen as the first step. Surgical treatment is reserved for cases of failure of conservative treatment with persistence of pain and mass. The case presented concerns an 18-year-old soccer player suffering from bilateral adductor longus (AL) MOT results following two different sports injuries. The patient reports the appearance of swelling and palpable mass at the proximal and medial region of the thigh, about 2 cm from the pubic symphysis, along the course of the adductor magnus. The radiological investigation showed the presence of a calcification along the course of the right and left AL muscles. Surgical treatment was considered for the right thigh injury, being symptomatic 1 year after the onset and refractory to other treatments. At 3 months of follow-up, the patient was asymptomatic and completed the rehabilitation program for the recovery of muscle strength and range of motion (ROM). In cases where MOT manifests with resistant pain, ROM restriction and daily activity reduction, surgical excision is the preferred option.

Immunosenescence, vascular aging, and brain aging, all characterized by elevated levels of inflammatory markers, are thought to share a common pathogenetic pathway: inflamm-aging. Retrospective cross-sectional analysis was conducted using data from the Mugello study (Tuscany, Italy), a representative Italian cohort of free-living nonagenarians. to assess the association between specific peripheral inflammation markers derived from white blood cell counts, and the diagnosis of dementia. All the variables of interest were reported for 411 subjects (110 males and 301 females) out of 475 enrolled in the study. Anamnestic dementia diagnosis was obtained from clinical certificate and confirmed by a General Practitioner, whereas leukocyte ratios were directly calculated from white blood cell counts. Body mass index and comorbidities were considered potential confounders. Diagnosis of any type dementia was certified in 73 cases (17.8%). Subjects affected by dementia were older, more frequently reported a previous stroke, had lower body mass index, and lower Mini-Mental-State-Examination score. Moreover, they had a higher lymphocyte count and lymphocyte-to-monocyte ratio compared to the non-demented nonagenarians. We found that higher levels of lymphocyte counts are cross-sectionally associated with a clinical diagnosis of dementia. Furthermore, lymphocyte-to-monocyte ratio is directly associated with any type of dementia, independently of age, sex, lymphocyte count, and comorbidities. Lymphocyte-to-monocyte ratio may be considered a marker of immunological changes in the brain of dementia patients; moreover, it is low-cost, and easily available, thus enabling comparisons among different studies and populations, although the timeline and the extent of lymphocyte-to-monocyte ratio role in dementia development must be further investigated.

Background Knowledge about sexual health, difficulty with sexual activity and intimacy (sexual difficulty), in people with hemophilia is little understood. Objectives The objectives were to determine the prevalence of sexual difficulty in people living with hemophilia (PWH) compared to people with no bleeding disorders (PWNoBD), and to determine factors associated with it. Methods This was an analysis of the PROBE study. We recruited individuals who had hemophilia A or B (PWH) and PWNoBD who were 18 years old or older. We calculated proportions of participants with sexual difficulty and odds ratios (ORs) adjusted for sex and age with 95% confidence intervals. Results There were 2007 PWH and 1972 PWNoBD. Mean (standard deviation) age was 41 (15) years in PWH and 42 (13) years in PWNoBD. Sexual difficulty was reported in 302 (15.1%) PWH and 79 (4.0%) PWNoBD. The odds of sexual difficulty were significantly higher in PWH (OR 3.82, 95% CI 2.85, 5.11). Among PWH, older age, experiencing acute or chronic pain in the past 12 months, bleeds within the past two weeks, ≥3 spontaneous joint bleeds (past six months), limitation of range of motion of any joints, and any life- or limb-threatening bleeds in the past 12 months were associated with sexual difficulty. Conclusions Sexual difficulty is more prevalent in people living with hemophilia and associated with markers of disease severity. Sexual health issues should be incorporated in comprehensive hemophilia care, future research, and hemophilia related health policy.

We have an academic medical center (AMC), an associated community-based hospital (CBH) and several ambulatory care centers which are being prepared to provide same day discharge (SDD) total joint arthroplasty (TJA) and unicompartmental knee arthroplasty (UKA). The near-capacity AMC cared for medically and technically complicated TJA patients. The CBH wanted to increase volume, improve margins, and become a center of excellence with an efficient hospital outpatient department and SDD TJA experience. Methods We transitioned primary, uncomplicated TJA, UKA, and minimally invasive TJA to the CBH. Revision surgeries, patients with extensive comorbidities, and complex primaries were performed at the AMC. Protocols were developed to facilitate SDD UKA and total hip arthroplasty (THA) as well as rapid recovery protocols for total knee arthroplasty (TKA) at both hospitals. A protocol-based system was put in place to make both hospitals ready for the removal of TKA from the Inpatient-Only list to avoid Quality Improvement Organization and possible resultant Recovery Audit Contractor audits if referred after implementation. Results The CBH volume increased 36.7% (+239). AMC volume slightly decreased (−0.46%, −5) resulting in an increase in margin contribution for the system. CBH quality metrics (surgical site infections, length of stay, readmissions, and mortality) were improved. Surgeon satisfaction improved as their volume, efficiency, quality metrics, and finances were enhanced. Although CBH per case revenue was 80.3% and 74.4% of the AMC for THA and TKA, net margins were 3.6% and 18.8% higher for THA and TKA, respectively. Increased efficiency, lower hospital cost, and higher volume at the CBH allowed for an increase in revenue despite lower reimbursement per case. Conclusion This strategy will help hospital systems improve net margins while improving patient care despite lower net revenue per TJA episode. These strategies will become increasingly important going forward with the transition of higher numbers of TJA patients to outpatient which will be subjected to further decreases in net revenue per patient.

No abstract available

Introduction: One of the most feared side effects of radiotherapy (RT) in the setting of breast cancer (BC) patients is cardiac toxicity. This side effect can jeopardize the quality of life (QoL) of long-term survivors. The impact of modern techniques of RT such as deep inspiration breath hold (DIBH) have dramatically changed this setting. We report and discuss the results of the literature overview of this paper. Materials and methods: Literature references were obtained with a PubMed query, hand searching, and clinicaltrials.gov. Results: We reported and discussed the toxicity of RT and the improvements due to the modern techniques in the setting of BC patients. Conclusions: BC patients often have a long life expectancy, thus the RT should aim at limiting toxicities and at the same time maintaining the same high cure rates. Further studies are needed to evaluate the risk–benefit ratio to identify patients at higher risk and to tailor the treatment choices.

Purpose During the COVID-19 pandemic, elective thyroid surgery is experiencing delays. The problem is that the COVID-19 pandemic is ongoing. The research purposes were to systematically collect the literature data on the characteristics of those thyroid operations performed and to assess the safety/risks associated with thyroid surgery during the COVID-19 pandemic. Methods We used all the procedures consistent with the PRISMA guidelines. A comprehensive literature in MEDLINE (PubMed) and Scopus was made using ‘‘Thyroid’’ and “coronavirus” as search terms. Results Of a total of 293 articles identified, 9 studies met the inclusion criteria. The total number of patients undergoing thyroid surgery was 2217. The indication for surgery was malignancy in 1347 cases (60.8%). Screening protocols varied depending on hospital protocol and maximum levels of personal protection equipment were adopted. The hospital length of stay was 2–3 days. Total thyroidectomy was chosen for 1557 patients (1557/1868, 83.4%), of which 596 procedures (596/1558, 38.3%) were combined with lymph node dissections. Cross-infections were registered in 14 cases (14/721, 1.9%), of which three (3/721, 0.4%) with severe pulmonary complications of COVID-19. 377 patients (377/1868, 20.2%) had complications after surgery, of which 285 (285/377, 75.6%) hypoparathyroidism and 71 (71/377, 18.8%) recurrent laryngeal nerve injury. Conclusion The risk of SARS-CoV-2 transmission after thyroid surgery is relatively low. Our study could promote the restart of planned thyroid surgery due to COVID-19. Future studies are warranted to obtain more solid data about the risk of complications after thyroid surgery during the COVID-19 era.

BACKGROUND Patients with bipolar spectrum disorders (BSDs) exhibit an increased risk of Parkinson's disease (PD). OBJECTIVE The aim is to investigate whether a previous diagnosis of BSDs influences the phenotype of PD. METHODS Of 2660 PD patients followed for at least 6 years (6-27), 250 (BSD-PD) had BSDs, 6-20 years before PD diagnosis; 48%-43% had a PD or BSD family history, and 34 carried glucocerebrosidase (GBA) and Parkin (PRKN) mutations. The cohort was split into a subset of 213 BSD-PD patients, compared with 426 matched PD patients without BSDs, and a subset of 34 BSD-PD and 79 PD patients carrying GBA or PRKN mutations. Carriers of mutations absent in BSD-PD patients and of synuclein triplication were excluded. Structured clinical interviews and mood disorder questionnaires assessed BSDs. Linear mixed models evaluated the assessment scales over time. Thirteen BSD-PD patients underwent subthalamic nucleus deep brain stimulation (STN-DBS) and were compared with 27 matched STN-DBS-treated PD patients. RESULTS Compared to PD patients, BSD-PD showed (1) higher frequency of family history of PD (odds ratio [OR] 3.31; 2.32-4.71) and BSDs (OR 6.20; 4.11-9.35) 5); (2) higher incidence of impulse control disorders (hazard ratio [HR] 5.95, 3.89-9.09); (3) higher frequency of functional disorders occurring before PD therapy (HR, 5.67, 3.95-8.15); (4) earlier occurrence of delusions or mild dementia (HR, 7.70, 5.55-10.69; HR, 1.43, 1.16-1.75); and (5) earlier mortality (1.48; 1.11-1.97). Genetic BSD-PD subjects exhibited clinical features indistinguishable from nongenetic BSD-PD subjects. STN-DBS-treated BSD-PD patients showed no improvements in quality of life compared to the control group. CONCLUSIONS BSDs as a prodrome to PD unfavorably shape their course and are associated with detrimental neuropsychiatric features and treatment outcomes. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

BACKGROUND Pediatric brain arteriovenous malformations (AVMs) are a significant cause of morbidity but the role of multimodal therapy in the treatment of these lesions is not well understood. OBJECTIVE To compare the outcomes of stereotactic radiosurgery (SRS) with and without prior embolization for pediatric AVMs. METHODS We retrospectively evaluated the International Radiosurgery Research Foundation pediatric AVM database. AVMs were categorized, based on use of pre-embolization (E + SRS) or lack thereof (SRS-only). Outcomes were compared in unadjusted and inverse probability weight (IPW)-adjusted models. Favorable outcome was defined as obliteration without post-SRS hemorrhage or permanent radiation-induced changes (RIC). RESULTS The E + SRS and SRS-only cohorts comprised 91 and 448 patients, respectively. In unadjusted models, the SRS-only cohort had higher rates of obliteration (68.5% vs 43.3%

In a Phase 2 clinical trial, we aimed to determine the lutetium-177 [177Lu]-PSMA-617 activity and the clinical utility of levels of plasma androgen receptor (AR) gene in patients with heavily pretreated metastatic castration-resistant prostate cancer (mCRPC). We determined AR copy number in pretreatment plasma samples. We used logistic regression to estimate the odds ratio (OR) and 95% confidence intervals (95% CIs) in order to evaluate the independent relevance of AR status and to evaluate patients with early progressive disease (PD) defined as treatment interruption occurring within 4 months after the start of 177Lu-PSMA-617. Twelve of the 15 (80%) with AR gene gain and 5 of the 25 (20%) patients with no gain of AR had early PD (p = 0.0002). The OR for patients without PSA response having AR gain was 3.69 (95% CI 0.83–16.36, p = 0.085). The OR for patients with early PD having AR gain was 16.00, (95% CI 3.23–79.27, p = 0.0007). Overall, median PFS and OS were 7.5 and 12.4 months, respectively. AR-gained had a significant shorter OS compared to AR-normal patients (7.4 vs 19.1 months, p = 0.020). No treatment interruptions due to adverse effects were reported. Plasma AR status helped to indicate mCRPC with early resistance to 177Lu-PSMA-617. NCT03454750.

Background: Glucocorticoid therapy has emerged as an effective therapeutic option in hospitalized patients with coronavirus disease 2019 (COVID-19). This study aimed to focus on the impact of relevant clinical and laboratory factors on the protective effect of glucocorticoids on mortality. Methods: A sub-analysis was performed of the multicenter Cardio-COVID-Italy registry, enrolling consecutive patients with COVID-19 admitted to 13 Italian cardiology units between 01 March 2020 and 09 April 2020. The primary endpoint was in-hospital mortality. Results: A total of 706 COVID-19 patients were included (349 treated with glucocorticoids, 357 not treated with glucocorticoids). After adjustment for relevant covariates, use of glucocorticoids was associated with a lower risk of in-hospital mortality (adjusted HR 0.44; 95% CI 0.26–0.72; p = 0.001). A significant interaction was observed between the protective effect of glucocorticoids on mortality and PaO2/FiO2 ratio on admission (p = 0.042), oxygen saturation on admission (p = 0.017), and peak CRP (0.023). Such protective effects of glucocorticoids were mainly observed in patients with lower PaO2/FiO2 ratio (100 mg/L). Conclusions: The protective effects of glucocorticoids on mortality in COVID-19 were more evident among patients with worse respiratory parameters and higher systemic inflammation.

The recent literature on intrahepatic cholestasis of pregnancy raises questions on the best management of such a disease. Improved evidence might be achieved by meta-analyses.Providing data for allowing individual patients meta-analyses and aggregate data meta-analyses.Data were collected retrospectively at the Fabia Mater Hospital of Rome (Italy), between 2013 and 2018. Several variables were collected and analyzed according to low-level bile acid (less than 40 μmol/L) and high-level bile acid (at least 40 μmol/L). Eighty-three cases of pregnancy cholestasis, diagnosed according to itching symptoms and excluding bile diseases, were collected and analyzed, both descriptively and inferentially.The analyzed data do not provide significant evidence supporting the use of ursodeoxycholic acid to prevent composite adverse fetal outcomes but they can be included in further meta-analyses.

High-quality evidence guiding optimal transfusion and other supportive therapies to reduce bleeding is needed to improve outcomes for patients with either severe bleeding or hemostatic disorders that are associated with poor outcomes. Alongside challenges in performing high-quality clinical trials in patient populations who are at risk of bleeding or who are actively bleeding, the interpretation of research evaluating hemostatic agents has been limited by inconsistency in the choice of primary trial outcomes. This lack of standardization of primary endpoints or outcomes decreases the ability of clinicians to assess the validity of endpoints and compare research results across studies, impairs meta-analytic efforts, and, ultimately, delays the translation of research results into clinical practice. To address this challenge, an international panel of experts was convened by the National Heart Lung and Blood Institute and the US Department of Defense on September 23 and 24, 2019, to develop expert opinion, consensus-based recommendations for primary clinical trial outcomes for pivotal trials in pediatric and adult patients with six categories in various clinical settings. This publication documents the conference proceedings from the workshop funded by the National Heart Lung and Blood Institute and the US Department of Defense that consolidated expert opinion regarding clinically meaningful outcomes across a wide range of disciplines to provide guidance for outcomes of future trials of hemostatic products and agents for patients with active bleeding.

Congenital heart disease (CHD) and cardiomyopathies represent the two most important causes of paediatric heart failure (HF) in developed countries. We made a review of the literature on pathophysiology and clinical presentation of paediatric HF in children with CHD. Two main pathophysiologic models can be identified: the 'over-circulation failure', characterised by signs and symptoms of congestion or hypoperfusion, due respectively to volume or pressure overload, and the 'pump failure'. CONCLUSIONS: The comprehension of the HF pathophysiology in paediatric patients with CHD is of paramount importance for the optimal management and for addressing the best therapeutic choices.

This experimental study aims to evaluate and validate the effectiveness of the proposed application method in the use of "focused mechanical vibrations" for the treatment of muscle spasticity. The basic concept of this study is that in spasticity, by specifically stimulating some clearly identifiable trigger points of the body, better results are obtained; in fact, with the localized mechanical-sound vibrations, by positioning the handpiece for the treatment on those specific points, immediate generalized relaxation of the entire spastic muscle is obtained through reflex pathways. To evaluate this operative reality we treated 5 subjects affected by neurological pathology with spasticity and at T0 time (before treatment) and at T1 time (immediately after treatment), they were assessed with Ashworth Scale, Passive joint evaluation, Evaluation of active motility, Test of Bahkta (for non-functioning hand), surface electromyography The subjects were treated with a 120Hz vibratory therapy handpiece for a total time of 15 minutes The data showed us a clear improvement of the parameters lost in the exam, in the less serious patients and a good improvement also in the most serious subjects.

Introduction The use of pharmacokinetic assessment for optimal prophylactic dosing of factor concentrates in haemophilia has gained increasing enthusiasm over the last decade. However, blood sampling on several occasions is burdensome and limited sampling using population-based PK is appealing. Aim To compare the pharmacokinetics and dosing recommendations for prophylaxis using six-point single subject versus population-based method (WAPPS-Hemo) for simoctocog alfa (Nuwiq® ). Methods Twelve adult patients with severe haemophilia A received a factor VIII (FVIII) dose of ≈50 IU/kg, and the activity was measured pre-infusion and at 30 min, 6, 9, 24 and 48 h post-infusion. Half-life (t1 /2 ), weight-normalized AUC and time to troughs of 5%, 3% and 1% were calculated. The correlation between the PK algorithms was assessed using intraclass correlations (ICC) and dosing estimations were provided. Results WAPPS-Hemo yielded a slightly longer mean t1 /2 , but the overall correlation between the methods was good (ICC ≥0.79) The time to troughs of 5%, 3% and 1% showed ICCs ≥0.86. For all variables, the most converging limited time point was 6+48 h. Additional time points did not improve the correlation. Despite similar pharmacokinetics, the mean estimated dose for a specific trough level varied from 60% less to 20% more using the population-based approach. The time to 1% and the corresponding dose was sensitive to the baseline assumption. Conclusion Our data support the use of population-based PK for patients on simoctocog alfa prophylaxis but also indicates differences, stressing the importance of the sampling scheme and monitoring actual FVIII levels achieved.

There is limited research in adolescents at risk for psychosis. The new Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition attenuated psychosis syndrome (DSM-5 APS) criteria have not been validated in this group. We conducted a RECORD-compliant, real-world, prospective, 5-year cohort study addressing clinical profile, transition to psychosis, and prognostic accuracy of DSM-5 APS in help-seeking inpatient/outpatient adolescents accessing Children and Adolescent Neuropsychiatric services at IRCCS Mondino Foundation (Pavia, Lombardy, Italy) between 2012 and 2019. About 243 adolescents (31 early-onset psychosis [EOP]; 110 meeting DSM-5 APS criteria, DSM-5 APS; 102 not meeting psychotic or DSM-5 APS criteria, non-APS) were included. At baseline, DSM-5 APS adolescents (aged 15.4 ± 1.6) had on average 2.3 comorbid disorders (higher than EOP/non-APS, P < .001). DSM-5 APS adolescents had an intermediate psychopathological profile between non-APS/EOP (P < .001) and worsen Clinical Global Impression-Severity than non-APS (P < .001). DSM-5 APS functioning was intermediate between non-APS and EOP. 39.1% of DSM-5 APS were treated with psychotropic drugs (average = 64 days); 53.6% received psychotherapy. Follow-up of DSM-5 APS and non-APS groups lasted 33 and 26 months, respectively (median). The cumulative risk of transition at 1–5 years was 13%, 17%, 24.2%, 26.8%, and 26.8% in the DSM-5 APS group, 0%, 0%, 3.2%, 3.2%, and 3.2% in the non-APS group. The 5-year prognostic accuracy of the DSM-5 APS in adolescent was adequate (area under the curve = 0.77; Harrell’s C = 0.736, 95%CI 0.697–0.775), with high sensitivity (91.3%) and suboptimal specificity (63.2%). The DSM-5 APS diagnosis can be used to detect help-seeking adolescents at risk of psychosis and predict their long-term outcomes. Future research should consolidate these findings.

Background The impact of glioma location on quality of life (QOL) has not been conclusively studied, possibly due to the prohibitively high sample size that standard statistical analyses would require and the inherent heterogeneity of this disease. By using a novel algorithm, we investigated the impact of tumor location on QOL in a limited set of 53 consecutive patients. Methods The glial tumors of 53 consecutive patients were segmented and registered to a standardized atlas. The Euclidian distance between 90 brain regions and each tumor's margin was calculated and correlated to the patient's self-reported QOL as measured by the Sherbrooke Neuro-Oncology Assessment Scale questionnaire. Results QOL was not correlated to tumor volume, though a significant correlation was observed with its proximity to these areas: right supramarginal gyrus, right rolandic operculum, right superior temporal gyrus, right middle temporal gyrus, right angular gyrus, and right inferior parietal lobule. Interestingly, all identified areas are in the right hemisphere, and localized in the temporoparietal region. We postulate that the adverse relation between proximity to these areas and QOL results from disruption in visuospatial functioning. Conclusions Although the areas identified in this study are traditionally considered non-eloquent areas, tumor proximity to these regions showed more impact on QOL than any other brain regions. We postulate that this effect is mediated via an adverse impact on the visuospatial functioning.

BACKGROUND AND PURPOSE: CTA has shown limited accuracy and reliability in distinguishing tandem occlusions and pseudo-occlusions on initial acute stroke imaging. The utility of early and delayed contrast-enhanced MRA in this setting is unknown. We aimed to assess the accuracy and reliability of early and delayed contrast-enhanced MRA for carotid bulb patency in patients with acute ischemic stroke. MATERIALS AND METHODS: We retrospectively reviewed patients who had ICA occlusion and underwent thrombectomy with preprocedural early and delayed contrast-enhanced MRA in a single comprehensive stroke center. During 2 sessions, 10 raters independently assessed 32 cases with early contrast-enhanced MRA (with an additional delayed contrast-enhanced MRA sequence during the second reading session). Their judgments were compared with DSA as a reference standard. Accuracy and interrater agreement were measured. Five raters undertook a third reading session to assess intrarater agreement. RESULTS: Accuracy for the assessment of carotid bulb patency with early contrast-enhanced MRA was limited (69%; 95% CI, 59%–79%), with moderate interrater agreement (κ = 0.42; 95% CI, 0.27–0.55). The second reading with an additional delayed contrast-enhanced MRA sequence improved both accuracy (82%; 95% CI, 73%–91%; P < .001) (raters corrected 43%–77% of incorrect diagnoses with early contrast-enhanced MRA alone; mean = 59%) and interrater agreement (κ = 0.56; 95% CI, 0.41–0.73; P = .07). Intrarater agreement was almost perfect, substantial, and moderate for 3, 1, and 1 raters. CONCLUSIONS: Early contrast-enhanced MRA has limited accuracy and repeatability for the evaluation of carotid bulb patency in acute ischemic stroke. The additional delayed contrast-enhanced MRA sequence may improve accuracy and reliability.

OBJECTIVES Management of resternotomy is often a difficult challenge in patients with congenital diseases who have undergone multiple sternotomies. Our goal was to report our single-centre experience with carotid cannulation using a graft interposed during redo sternotomy in complex cardiac reintervention procedures. METHODS We performed a retrospective review of all patients who had undergone complex redo sternotomies between January 2019 and May 2020 utilizing a cervical cannulation technique with a Gore-Tex graft interposed on the carotid artery. We classified our population study on the basis of the primary diagnosis and the type of surgery. The primary outcomes of our analysis were the evaluation of the safety of the procedure in terms of survival and freedom from neurological events. RESULTS We analysed 22 patients who had undergone previous complex operations. The median age and weight at the time of reintervention were 130.35 (range 0.46–435) months and 31.5 (range 2.2–85) kg, respectively. Composite graft carotid cannulation provided adequate arterial flow in all patients with a median arterial flow of 3.5 l/min/m2 (range 0.6–6). One major cardiac injury occurred during sternotomy when emergency cardiopulmonary bypass (CPB) was initiated. Moreover, during their hospital stays, all patients had an uneventful recovery without neurological or vascular complications and no cervical wound infections. CONCLUSIONS Carotid cannulation using interposition of a side graft on the common carotid artery for arterial inflow is a reliable and safe method for initiation of CPB in complex redo surgeries in patients with congenital disease. Complications directly associated with this type of cannulation are uncommon and allow surgical re-entry with overall low risks.

Background Coronavirus Disease 2019 (COVID-19) is a pandemic affecting all countries in the world. Italy has been particularly afflicted by the health emergency, and since the peak phase has passed, major concern regarding medium to long term complications due to COVID-19 is arising. Little is known in literature regarding thromboembolic complications once healed after COVID-19. Case presentation A 51-year-old patient recovered from COVID-19 pneumonia complicated by pulmonary embolism (PE) came to the hospital for palpitations and chest pain. Although he was on treatment dose of direct oral anticoagulation (DOAC), massive recurrent PE was diagnosed. Conclusion In the early post COVID-19 era, the question remains regarding the efficacy of DOACs in COVID-19 patients.

Background Pulmonary embolism (PE) has been described in coronavirus disease 2019 (COVID-19) critically ill patients, but the evidence from more heterogeneous cohorts is limited. Methods Data were retrospectively obtained from consecutive COVID-19 patients admitted to 13 Cardiology Units in Italy, from March 1st to April 9th, 2020, and followed until in-hospital death, discharge, or April 23rd, 2020. The association of baseline variables with computed tomography-confirmed PE was investigated by Cox hazards regression analysis. The relationship between d-dimer levels and PE incidence was evaluated using restricted cubic splines models. Results The study included 689 patients (67.3 ± 13.2 year-old, 69.4% males), of whom 43.6% were non-invasively ventilated and 15.8% invasively. 52 (7.5%) had PE over 15 (9–24) days of follow-up. Compared with those without PE, these subjects had younger age, higher BMI, less often heart failure and chronic kidney disease, more severe cardio-pulmonary involvement, and higher admission d-dimer [4344 (1099–15,118) vs. 818.5 (417–1460) ng/mL, p p p = 0.06). In multivariate regression, only d-dimer was associated with PE (HR 1.72, 95% CI 1.13–2.62; p = 0.01). The relation between d-dimer concentrations and PE incidence was linear, without inflection point. Only two subjects had a baseline d-dimer Conclusions PE occurs in a sizable proportion of hospitalized COVID-19 patients. The implications of bleeding events and the role of d-dimer in this population need to be clarified. Graphic abstract

Aims Myocardial injury (MI) in coronavirus disease‐19 (COVID‐19) is quite prevalent at admission and affects prognosis. Little is known about troponin trajectories and their prognostic role. We aimed to describe the early in‐hospital evolution of MI and its prognostic impact. Methods and results We performed an analysis from an Italian multicentre study enrolling COVID‐19 patients, hospitalized from 1 March to 9 April 2020. MI was defined as increased troponin level. The first troponin was tested within 24 h from admission, the second one between 24 and 48 h. Elevated troponin was defined as values above the 99th percentile of normal values. Patients were divided in four groups: normal, normal then elevated, elevated then normal, and elevated. The outcome was in‐hospital death. The study population included 197 patients; 41% had normal troponin at both evaluations, 44% had elevated troponin at both assessments, 8% had normal then elevated troponin, and 7% had elevated then normal troponin. During hospitalization, 49 (25%) patients died. Patients with incident MI, with persistent MI, and with MI only at admission had a higher risk of death compared with those with normal troponin at both evaluations (P

Purpose: Meningioma is a benign tumor, more frequent in female population. During pregnancy, distinguishing a meningioma from other common conditions presenting with similar symptoms (headache, vomiting, visual impairment) is challenging. Moreover, the management must consider not only maternal but also fetal health. The rarity of the condition does not allow to define the features to which look in order to stratify the risk for the need of surgery during pregnancy. We reported three cases of meningioma in pregnant women treated at our department and reviewed those previously reported in the literature. The aim of this review is to evaluate which factors are more determinant in such management. Methods: Electronic databases were searched from year 2000 until June 2020, to identify clinical studies on management of meningioma diagnosed during pregnancy. The primary outcome was surgical timing. Secondary outcomes were delivery methods, maternal and neonatal outcomes. Results: Surgery after pregnancy is more frequently performed in PR + tumor (p-value 0.038) and with HA (p-value 0.0445), as well as in meningioma diagnosed during the third trimester, compared to those diagnosed before (p-value 0.0012). Surgery during pregnancy was more frequent in patients with visual loss (p-value 0.006). No significant differences were found in surgical management, according to age, WHO grade, tumor location, lesion diameter and ER positivity. Delivery method is independent from both hormonal receptor status and main symptoms, but women who had neurosurgery during pregnancy delivered more frequently with spontaneous vaginal delivery (p-value

Aims To assess the clinical relevance of a history of atrial fibrillation (AF) in hospitalized patients with coronavirus disease 2019 (COVID-19). Methods and results We enrolled 696 consecutive patients (mean age 67.4 ± 13.2 years, 69.7% males) admitted for COVID-19 in 13 Italian cardiology centres between 1 March and 9 April 2020. One hundred and six patients (15%) had a history of AF and the median hospitalization length was 14 days (interquartile range 9–24). Patients with a history of AF were older and with a higher burden of cardiovascular risk factors. Compared to patients without AF, they showed a higher rate of in-hospital death (38.7% vs. 20.8%; P 0.05 for both) and was not related to stroke or bleeding events. Conclusion Among hospitalized patients with COVID-19, a history of AF contributes to worse clinical course with a higher mortality and in-hospital events including new-onset AF, acute HF, and multiorgan failure. The mortality risk remains significant after adjustment for variables associated with COVID-19 severity and comorbidities.

Hepatic hydrothorax represents a rare complication of portal hypertension among adult cirrhotic patients. Here we describe a pediatric case of hepatic hydrothorax, observed in a biliary atresia infant. The child presented with recurrent right side pleural effusion, after a successful Kasai portoenterostomy with restoration of bile flow and without overt signs of hepatic failure. Recurrence of hepatic hydrothorax led the patient to liver transplant despite a low Pediatric End-stage Liver Disease value. Although rare, hepatic hydrothorax can also occur in children and should be suspected in patients with portal hypertension and respiratory distress. HH may be an indication for liver transplantation.

Purpose: To present visual outcomes of the first two Italian patients with RPE65-related inherited retinal dystrophy (RPE65-IRD) treated with voretigene neparvovec (VN). Methods: Two pediatric patients with RPE65-IRD were treated with VN in both eyes. Patients were evaluated by best-corrected visual acuity (BCVA), full-field stimulus threshold (FST) test, semiautomated kinetic visual field (SKVF), microperimetry, and chromatic pupillometry over 6 months. Results: No complications occurred in the first patient, whereas in the second a subreti-nal hemorrhage was observed in the first treated eye, and excessive resistance to drug injection occurred during treatment of the second eye. BCVA improved by at least one Early Treatment Diabetic Retinopathy Study line in all treated eyes. The FST test and SKVF showed clinically significant improvements in all eyes (i.e., change of light sensitivity > 10 decibels; area enlargement of at least 20%). Moreover, microperimetry showed better fixation stability. Finally, chromatic pupillometry showed increases in pupillary constric-tion that ranged from 10% to 20%. All visual changes remained stable during follow-up. Conclusions: The first VN treatments in two pediatric Italian patients in clinical practice showed significant improvements in visual outcomes, even in the case of surgical complications, which spontaneously recovered without sequelae. Translational Relevance: These findings with VN in patients with RPE65-IRD confirm the results of clinical trials.

Fever and pain are challenging symptoms in children and adolescents and are common reasons for consultations in primary care and hospital. Paracetamol and ibuprofen are currently the only recommended drugs for treating fever in Italy, but the therapeutic approaches are discrepant in the different settings. In Italy, paracetamol and ibuprofen are the most prescribed analgesics for acute mild–moderate pain in children; however, their use is often inappropriate in that fever is over-treated and pain is under-treated. An Italian board of experts analyzed the motivations for the misalignment between daily practice and guidelines of fever and acute mild–moderate pain management of the territory and hospitals. The expert opinion consensus process underscored the appropriate use of paracetamol and ibuprofen according to clinical scenarios, patients’ profiles, and the safety features of the drugs. Although patients’ profiles can indicate different benefits from paracetamol or ibuprofen, critical issues of fever and acute mild–moderate pain management persist in primary care and hospitals. These expert opinion consensus statements can be an across-the-board tool to harmonize the routine practice between the territory and hospitals, especially under special conditions (at-risk for dehydration, coagulation disorder patients, etc.). It can also promote educational activity about fever and acute mild–moderate pain management to enhance the milestones already achieved by Italian pediatricians.

Background: The perturbation of phosphate homeostasis portends unfavorable outcomes in chronic kidney disease (CKD). However, the absence of randomized clinical trials (RCT) fuels the discussion of whether phosphate or some other phosphorous-related factor(s) such as fibroblast growth factor 23 (FGF-23) mediates the cardiovascular and systemic toxicity. We herein test whether the fractional excretion of phosphate (FeP) as a marker of renal stress to excrete phosphorous predicts unfavorable outcomes in CKD patients. Methods: Retrospective, cross-sectional observational study. For current analysis, an historical cohort of 407 records of CKD stage 3b-5 patients attending between January 2010 and October 2015 at the Nephrology Unit of Solofra (AV), Italy were utilized. Demographic, clinical, laboratory, and outcome data were identified through the subjects&rsquo, medical records. We tested whether quartiles of FeP are associated with the risk of CKD progression or all causes of death. Parametric as well as non-parametric tests, linear and logistic regression, as well as survival analysis were utilized. Results: Overall, we investigated middle-age (mean 66.0, standard deviation 12.3 years) men and women (male 43%) with CKD stage 3b to 5 (creatinine clearance 32.0 (13.3) mL/min). Older age, lower diastolic blood pressure, poor renal function, as well as higher serum phosphate were associated with FeP. Patients with higher FeP were at an increased risk of starting dialysis or dying (hazard ratio 2.40, 95% confidence interval (1.44, 3.99)). Notably, when the two endpoints were analyzed separately, FeP was associated with renal but not all-cause survival. Conclusion: FeP is associated with ESRD, but not all-cause mortality risk in a large cohort of moderate to advanced CKD patients. Future efforts are required to validate FeP as a marker of nephron stress and risk factor for CKD progression in this high-risk population.