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During the coronavirus disease 2019 (COVID-19) pandemic, noninvasive respiratory support has played a central role in managing patients affected by moderate-to-severe acute hypoxemic respiratory failure, despite inadequate scientific evidence to support its usage. High-flow nasal cannula (HFNC) treatment has gained tremendous popularity because of its effectiveness in delivering a high fraction of humidified oxygen, which improves ventilatory efficiency and the respiratory pattern, as well as its reported high tolerability, ease of use, and application outside of ICUs. Nevertheless, the risk of infection transmission to health-care workers has raised some concerns about its use in the first wave of the pandemic outbreak, with controversial recommendations provided by different scientific societies. This narrative review provides an overview of the recent evidence on the physiologic rationale, risks, and benefits of using HFNC instead of conventional oxygen therapy and other types of noninvasive respiratory support devices, such as continuous positive airway pressure and noninvasive ventilation in patients affected by COVID-19 pneumonia with associated acute hypoxemic respiratory failure. It also summarizes the available evidence with regard to the clinical use of HFNC during the current pandemic and its reported outcomes, and highlights the risks of bioaerosol dispersion associated with HFNC use.

Protein pool turnover is a critically important cellular homeostatic component, yet it has been little explored in the context of heart failure (HF) pathophysiology. We employed in vivo 2H labeling/ proteome dynamics for non-biased discovery of turnover alterations involving functionally linked cardiac and plasma proteins in canine tachypacing-induced HF, an established preclinical model of dilated cardiomyopathy. Compared to control, dogs with congestive HF displayed bidirectional turnover changes of 28 cardiac proteins, i.e. reduced half-life of several key enzymes involved in glycolysis, homocysteine metabolism and glycogenesis, and increased half-life of proteins involved in proteolysis. Changes in plasma proteins were more modest: only 5 proteins, involved in various functions including proteolysis inhibition, hemoglobin, calcium and ferric-iron binding, displayed increased or decreased turnover rates. In other dogs undergoing cardiac tachypacing, we infused for 2 weeks the myokine Follistatin-like protein 1 (FSTL1), known for its ameliorative effects on HF-induced alterations. Proteome dynamics proved very sensitive in detecting the partial or complete prevention, by FSTL1, of cardiac and plasma protein turnover alterations. In conclusion, our study unveiled, for the first time in a large mammal, numerous HF-related alterations that may serve as the basis for future mechanistic research and/or as conceptually new molecular markers.

Purpose Pulmonary hamartoma is the most common benign tumor of the lung. We analyzed a 20-year historical series of patients with pulmonary hamartoma undergoing surgical resection, aiming to evaluate the characteristics, the outcomes, and the association between hamartoma and lung cancer. Methods It was a retrospective multicenter study including the data of all consecutive patients with pulmonary hamartoma undergoing surgical resection. The end-points were to evaluate: (i) the characteristics of hamartoma, (ii) outcomes, and (iii) whether hamartoma was a predictive factor for lung cancer development Results Our study population included 540 patients. Upfront surgical or endoscopic resection was performed in 385 (71%) cases while in the remaining 155 (29%) cases, the lesions were resected 20 ± 3.5 months later due to increase in size. In most cases, lung sparing resection was carried out including enucleation (n = 259; 48%) and wedge resection (n = 230; 43%) while 5 (1%) patients underwent endoscopic resection. Only two patients (0, 2%) had major complications. One patient (0.23%) had recurrence after endoscopic resection, while no cases of malignant degeneration were seen (mean follow-up:103.3 ± 93 months). Seventy-six patients (14%) had associated lung cancer, synchronous in 9 (12%) and metachronous in 67 (88%). Only age > 70-year-old (p = 0.0059) and smokers > 20 cigarettes/day (p Conclusion PH was a benign tumor, with no evidence of recurrence and/or of malignant degeneration after resection. The association between hamartoma and lung cancer was a spurious phenomenon due to common risk factors.

Purpose: Fibroblast activation protein (FAP)-expressing cancer-associated fibroblasts confer treatment resistance, promote metastasis and immunosuppression. Because FAP is overexpressed in many cancers, radiolabeled molecules targeting FAP are studied for their use as pan-cancer theranostic agents. This study aims to establish the spectrum of FAP expression across various cancers by immunohistochemistry and to explore whether gallium-68 FAPi-46 (68Ga-FAPi-46) PET biodistribution faithfully reflects FAP expression from resected cancer and non-cancer specimens. Methods: We conducted a FAP expression screening by using immunohistochemistry on a pan-cancer human tissue microarray (TMA) (141 patients, 14 different types of cancer) and an interim analysis of a prospective exploratory imaging trial in cancer patients. Volunteer patients underwent one whole body 68Ga-FAPi-46 PET/CT scan and subsequently, surgical resection of their primary tumor and/or metastasis. 68Ga-FAPi-46 PET maximum standardized uptake value (SUVmax and SUVmean) was correlated with FAP immunohistochemistry score in cancer and non-cancer tissues for each patient. Results: FAP was expressed across all 14 cancers types on TMA with variable intensity and frequency, ranging from 25 to 100% (mean 76.6±25.3%). Strong FAP expression was observed in 50-100% of cancers of the bile duct, bladder, colon, esophagus, stomach, lung, oropharynx, ovary and pancreas. Fifteen patients with various cancer types (colorectal (n = 4), head and neck (n = 3), pancreas (n = 2), breast (n = 2), stomach (n = 1), esophagus (n = 2) and uterus (n = 1)) underwent surgery following their 68Ga-FAPi-46 PET/CT scan within a mean time interval of 16.1±14.4 days. 68Ga-FAPi-46 SUVs and immunohistochemistry scores were higher in cancer than in normal tissue: mean SUVmax 7.7 vs 1.6 (p

Background Noninvasive ventilation (NIV) is indicated to treat respiratory acidosis due to exacerbation of chronic obstructive pulmonary disease (COPD). Recent nonrandomized studies also demonstrated some physiological effects of high-flow nasal therapy (HFNT) in COPD patients. We designed a prospective, unblinded, multicenter, randomized controlled trial to assess the noninferiority of HFNT compared to NIV with respect to the reduction of arterial partial pressure of carbon dioxide (PaCO2) in patients with hypercapnic acute respiratory failure with mild-to-moderate respiratory acidosis. Methods We will enroll adult patients with acute hypercapnic respiratory failure, as defined by arterial pH between 7.25 and 7.35 and PaCO2 ≥ 55 mmHg. Patients will be randomly assigned 1:1 to receive NIV or HFNT. NIV will be applied through a mask with a dedicated ventilator in pressure support mode. Positive end-expiratory pressure will be set at 3–5 cmH2O with inspiratory support to obtain a tidal volume between 6 and 8 ml/kg of ideal body weight. HFNT will be initially set at a temperature of 37 °C and a flow of 60 L/min. At 2 and 6 h we will assess arterial blood gases, vital parameters, respiratory rate, treatment intolerance and failure, need for endotracheal intubation, time spent under mechanical ventilation (both invasive and NIV), intensive care unit and hospital length of stay, and hospital mortality. Based on an α error of 5% and a β error of 80%, with a standard deviation for PaCO2 equal to 15 mmHg and a noninferiority limit of 10 mmHg, we computed a sample size of 56 patients. Considering potential drop-outs and nonparametric analysis, the final computed sample size was 80 patients (40 per group). Discussion HFNT is more comfortable than NIV in COPD patients recovering from an episode of exacerbation. If HFNT would not be inferior to NIV, HFNT could be considered as an alternative to NIV to treat COPD patients with mild-to-moderate respiratory acidosis. Trial registration ClinicalTrials.gov, NCT03370666. Registered on December 12, 2017. Electronic supplementary material The online version of this article (10.1186/s13063-019-3514-1) contains supplementary material, which is available to authorized users.

Summary Background Patients with systemic lupus erythematosus (SLE) are at risk of developing COVID-19 due to underlying immune abnormalities and regular use of immunosuppressant medications. We aimed to evaluate the presence of SARS-CoV-2 IgG antibodies in patients with SLE with or without previous COVID-19-related symptoms or RT-PCR-confirmed SARS-CoV-2 infection. Methods For this analysis, we included patients with SLE from two cohorts based in New York City: the Web-based Assessment of Autoimmune, Immune-Mediated and Rheumatic Patients during the COVID-19 pandemic (WARCOV) study; and the NYU Lupus Cohort (a prospective registry of patients at NYU Langone Health and NYC Health + Hospitals/Bellevue). Patients in both cohorts were tested for SARS-CoV-2 IgG antibodies via commercially available immunoassays, processed through hospital or outpatient laboratories. Patients recruited from the NYU Lupus Cohort, referred from affiliated providers, or admitted to hospital with COVID-19 were tested for SARS-CoV-2 IgG antibodies as part of routine surveillance during follow-up clinical visits. Findings 329 patients with SLE were included in this analysis, 146 from the WARCOV study and 183 from the NYU Lupus Cohort, and were tested for SARS-CoV-2 antibodies between April 29, 2020, and Feb 9, 2021. 309 (94%) were women and 91 (28%) were of Hispanic ethnicity. 51 (16%) of 329 patients had a positive SARS-CoV-2 IgG antibody test. Seropositive patients were more likely than seronegative patients to be Hispanic (24 [47%] of 51 vsz 67 [24%] of 278). Other demographic variables, SLE-specific factors, and immunosuppressant use were not associated with SARS-CoV-2 positivity. Of the 29 patients with COVID-19 previously confirmed by RT-PCR, 18 (62%) were on immunosuppressants; 24 (83%) of 29 patients tested positive for SARS-CoV-2 IgG antibodies. Of 17 patients who had symptoms of COVID-19 but negative concurrent RT-PCR testing, one (6%) developed an antibody response. Of 26 patients who had COVID-19-related symptoms but did not undergo RT-PCR testing, six (23%) developed an antibody response. Of 83 patients who had no symptoms of COVID-19 and no RT-PCR testing, four (5%) developed an antibody response. Among 36 patients who were initially SARS-CoV-2 IgG positive, the majority maintained reactivity serially (88% up to 10 weeks, 83% up to 20 weeks, and 80% up to 30 weeks). Seven (70%) of ten patients with confirmed COVID-19 had antibody positivity beyond 30 weeks from disease onset. Interpretation Most patients with SLE and confirmed COVID-19 were able to produce and maintain a serological response despite the use of a variety of immunosuppressants, providing reassurance about the efficacy and durability of humoral immunity and possible protection against re-infection with SARS-CoV-2. Funding National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, and Bloomberg Philanthropies COVID-19 Response Initiative Grant.

STUDY OBJECTIVES: To explore the association of continuous positive airway pressure (CPAP) adherence with clinical outcomes in patients with type 2 diabetes and obstructive sleep apnea in a real-world setting. METHODS: This was a retrospective study of patients with type 2 diabetes diagnosed with obstructive sleep apnea between 2010 and 2017. CPAP adherence (usage for ≥ 4 h/night for ≥ 70% of nights) was determined from the first CPAP report following the polysomnography. Data including estimated glomerular filtration rate, hemoglobin A1c, systolic and diastolic blood pressure, lipid panel, and incident cardiovascular/peripheral vascular/cerebrovascular events were extracted from medical records. Mixed-effects linear regression modeling of longitudinal repeated measures within patients was utilized for continuous outcomes, and logistic regression modeling was used for binary outcomes. Models were controlled for age, sex, body mass index, medications, and baseline levels of outcomes. RESULTS: Of the 1,295 patients, 260 (20.7%) were CPAP adherent, 318 (24.5%) were CPAP nonadherent, and 717 (55.3%) had insufficient data. The follow-up period was, on average, 2.5 (1.7) years. Compared to those who were CPAP nonadherent, those who were adherent had a significantly lower systolic blood pressure (β = −1.95 mm Hg, P = .001) and diastolic blood pressure (β = −2.33 mm Hg, P < .0001). Among the patients who were CPAP adherent, a 17% greater CPAP adherence was associated with a 2 mm Hg lower systolic blood pressure. Lipids, hemoglobin A1c, estimated glomerular filtration rate, and incident cardiovascular/peripheral vascular/cerebrovascular events were not different between the 2 groups. CONCLUSIONS: Achieving CPAP adherence in patients with type 2 diabetes and obstructive sleep apnea was associated with significantly lower blood pressure. Greater CPAP use within patients who were adherent was associated with lower systolic blood pressure. CITATION: Sheth U, Monson RS, Prasad B, et al. Association of continuous positive airway pressure adherence with complications in patients with type 2 diabetes and obstructive sleep apnea. J Clin Sleep Med. 2021;17(8):1563–1569.

Background Biobanks are imperative infrastructures, particularly during outbreaks, when there is an obligation to acquire and share knowledge as quick as possible to allow for implementation of science-based preventive, diagnostic, prognostic and therapeutic strategies. Methods We established a COVID-19 biobank with the aim of collecting high-quality and well-annotated human biospecimens, in the effort to understand the pathogenic mechanisms underlying COVID-19 and identify therapeutic targets (COVID-BioB, NCT04318366). Here we describe our experience and briefly review the characteristics of the biobanks for COVID-19 that have been so far established. Results A total of 46,677 samples have been collected from 913 participants (63.3% males, median [IQR] age 62.2 [51.2 - 74.0] years) since the beginning of the program. Most patients (66.9%) had been admitted to hospital for COVID-19, with a median length of stay of 15.0 (9.0 - 27.0) days. A minority of patients (13.3% of the total) had been admitted for other reasons and subsequently tested positive for SARS-CoV-2. The remainder were managed at home after being seen at the Emergency Department. Conclusions Having a solid research infrastructure already in place, along with flexibility and adaptability to new requirements, allowed for the quick building of a COVID-19 biobank that will help expand and share the knowledge of SARS-CoV-2.

Background Obesity and its relationship with higher rate of complications in orthopedic surgeries have been reported. There is no evidence of the relation between obesity and percutaneous foot surgery. Our objective was to evaluate obesity as a risk factor for complications and reoperations in percutaneous surgery of the hallux valgus. Methods A total 532 feet were retrospectively reviewed in which a percutaneous hallux valgus correction was performed. Complications and surgical reoperations were recorded. Patients were divided into 2 groups: BMI less and greater than 30 kg/m2. Results There were no differences in the rate of complications or reoperations. The total complication rate was 8%. Obesity as an isolated risk factor, presented aOR = 1.14 (95%CI 0.54–2.4, p = .714). The overall rate of reoperations was 9%. Obesity presented an aOR = 0.64 (95%CI 0.27–1.49, p = .31). Conclusion Obesity has not been associated with a higher rate of complications and reoperations in percutaneous hallux valgus surgery. It is a safe procedure and BMI should not influence in the prognosis. Level of evidence: Level III, retrospective comparative study.

Vesicoureteral reflux (VUR) is an abnormality frequently seen at a complete duplex system (DS). Operational correction is required and completed after the neonatal period when symptoms occur. This study aimed to evaluate the efficacy of Vantris and a need for additional surgery in children with DS VUR in a multicenter study. We performed retrospective analysis of prospectively acquired data, from 2009 to 2018, on 172 patients with a mean age of 3 years with VUR into either upper or lower moiety of the DS who underwent endoscopic correction utilizing Vantris at five centers worldwide. All patients were with primary VUR. The median follow-up was 7 years. Reflux was corrected in 122 patients (70%) after the first injection and 35 patients (20%) after the second injection. 15 patients (9%) failed endoscopic correction and required ureteral reimplantation. 13 patients suffered afebrile urinary tract infection, and 9 patients developed febrile urinary tract infection (UTI). 3 patients required partial nephrectomy of the poorly or non-functioning refluxing moiety following the failure of endoscopic correction. Our data shows that Vantris injection provides a high reflux resolution in a DS with VUR. Successful VUR resolution might spare some patients associated with VUR poorly functioning moieties further surgery.

Objective We describe a case of severe hypoglycemia in a 14-month-old child as a suspected adverse drug reaction (ADR) to nadolol, and we performed an analysis of the FDA Adverse Event Reporting System (FAERS) database. Although previous reports have identified the risk of severe hypoglycemia in children during treatment with β-blockers, little is known about hypoglycemia as an ADR in infants treated with nadolol. Moreover, the pharmacodynamic and pharmacokinetic profiles of nadolol in children aged less than 1 year old are still not fully known. Materials and methods We extracted all ADR reports involving nadolol from the FAERS database; in order to reduce the risk of bias, we only considered cases that exclusively reported nadolol as the suspect drug. We then selected cases of hypoglycemia in the pediatric population and conducted a manual deduplication. Results Upon FAERS database analysis, a total of 2,674 suspected ADR reports to nadolol were found. Of these, 1,950 (73%) were solely attributed to nadolol, and 63 of them were hypoglycemic events. A total of 47 reports included the relevant pediatric age (74.6%). After deduplication, we identified 25 cases (mean age: 3.65 years old); all of these reports were categorized as serious, and hospitalization was required in 15 cases. Conclusion Hypoglycemia is a reported life-threatening ADR associated with nadolol, especially in infants, in whom this drug should be used with caution.

Background Complicated parapneumonic effusions and empyema represent advanced stages of pleural infections and are characterized by a high mortality. Medical thoracoscopy is a safe and minimally invasive endoscopic technique prescribed to treat severe pleural infections. However, only a few studies evaluated its success rate. A systematic review of observational studies was performed to assess the efficacy of medical thoracoscopy in patients with complicated parapneumonic effusions and empyema, as well as its predictive factors. Methods A search of the scientific evidence was carried out using PubMed, EMBASE, and Cochrane Central Register of Controlled Trials. Articles describing observational studies on medical thoracoscopy in patients with parapneumonic effusions and empyema were selected. Results Eight studies met the inclusion criteria. The pooled treatment success rate of thoracoscopy was 85% (95% CI 80.0–90.0%; I2: 61.8%) when used as first-line intervention or after failure of chest tube. The pooled complication rate was 9.0% (95% CI 6.0–14.0%; I2: 58.8%). A pooled difference of treatment success of 9.0% (95% CI 1.0–18.0%) was found when post-thoracoscopy intra-pleural fibrinolysis was prescribed. Pooled success rate was higher in cases with pleural fluid culture negativity (pooled difference: 14.0%; 95% CI 4.0–24.0%). Conclusions Medical thoracoscopy is effective and safe when prescribed for complicated parapneumonic effusions and empyema. Bacteriological negativity of pleural effusion specimens and administration of adjuvant intra-pleural fibrinolysis after the procedure are associated with a higher success rate.

On January 25, 2018 a 5-car train derailed in Pioltello, 10 kilometers North-East of Milano City. A standardized post-hoc form was distributed to the hospitals involved in the management of the victims and allowed for an evaluation of the response to the incident.The management of the incident by EMS (Emergency Medical System) was effective in terms of organization of the scene and distribution of the patients, although the time for the first severe patient to reach the closest appropriate hospital was very long (2 hours). This can be partially explained by the extrication time.None of the alerted hospitals exceeded their capacity, as patients were distributed carefully among the hospitals. The overall outcome was quite satisfactory; no deaths were reported except for those on scene. Some responding hospitals reported that there was an over-activation based on the services ultimately needed. However this is common in MCIs, as an over-activation is preferable to an under-estimation. To address this concern, as more data are available, activation should be scaled down based on a plan established prior to it; this mechanism of scaling down seems to have failed in this event.It is of note that the highest performing hospitals underwent recently to an educational program on MCI management.

Background We devised a new strategy using suture traction to facilitate the management of primary spontaneous pneumothorax during uniportal thoracoscopy. To test its validity, we compared the outcomes of our modified technique with those of conventional three-port thoracoscopy. Methods This retrospective study included all 43 consecutive patients with primary spontaneous pneumothorax undergoing thoracoscopy between January 2017 and December 2019. They were divided within two groups: uniportal thoracoscopy using suture traction ( n = 21) and conventional 3-port thoracoscopy ( n = 22). Postoperative pain, paresthesia, patient satisfaction, and surgical outcomes were compared to test the validity of our technique. Results There were no significant differences in operative time (47 ± 4.8 vs. 43 ± 7.9 min), number of staples used (2.5 ± 0.9 vs. 2.3 ± 0.6), postoperative drainage (235 ± 15 vs. 240 ± 19 mL), chest tube drainage time (3.2 ± 0.8 vs. 3.4 ± 1.8 days), and hospital stay (4.2 ± 1.2 vs. 4.3 ± 0.9 days). However, uniportal thoracoscopy was associated with less pain at 24 ( p = 0.01), 48 ( p = 0.02), and 72 h ( p = 0.03) postoperatively, less paresthesia at 24 ( p = 0.03), 48 ( p = 0.02), and 72 h ( p = 0.02) postoperatively, and greater patient satisfaction at 24 ( p = 0.04), 48 ( p = 0.02), and 72 h ( p = 0.02) postoperatively. Conclusions Our technique may facilitate the use of uniportal thoracoscopy for treatment of primary spontaneous pneumothorax, reducing neurological sequelae and improving patient satisfaction compared to the traditional three-port thoracoscopy.

Introduction: Tracheostomy is a common procedure for management of tracheomalacia. However, the limitation to speak related to tracheostomy cannula could affect the quality of life. Objectives: we reported a new minimally invasive procedure to replace tracheostomy cannula with Montgomery T-tube to improve the ability of speaking. Methods: This is a single center study including all consecutive patients undergoing the replacement of standard tracheostomy cannula with T-tube for management of tracheomalacia. The end-points were to evaluate (a) the changes in Voice-related quality of Life (V-RQOL) before and after T-tube placement; and (b) the complications related to T-tube. Results: Eleven patients were included in the study. T-tube was placed using flexible bronchoscopy and laryngeal mask airway. A suture was inserted through the proximal end of T-tube. Once the stent was introduced with a clamp into the trachea, a traction was applied on the suture to facilitate the alignment of the upper end of the stent. The comparison of V-RQOL values before and after T-tube insertion showed a significant improvement in social/emotional (39.2±6.1 vs 66.8±1.9; P=.0001); physical functioning (21±5.7 vs 56.4±5.3; P=0.0001) and total V-RQOL scores (33.9+5.4 vs 61.3+6.1; P=0.0001). No complications were seen during the insertion of the stent. In two patients, T-tube was obstructed by mucus that resolved with aspiration using flexible bronchoscopy (mean follow-up: 18±10months). Conclusions: Our technique is simple and safe, not needing specific skills and/or cumbersome devices. The replacement of tracheostomy cannula with T-tube seems to improve the quality of voice without adding major complications.

Background: High-flow nasal oxygen (HFNO) improves exercise capacity, oxygen saturation, and symptoms in patients with chronic obstructive pulmonary disease (COPD). Due to the need of electricity supply, HFNO has not been applied during free ambulation. Objective: We evaluated whether HFNO delivered during walking by a battery-supplied portable device was more effective than usual portable oxygen in improving exercise capacity in patients with COPD and severe exercise limitation. The effects on 6-min walking tests (6MWTs) were the primary outcome. Methods: After a baseline 6MWT, 20 stable patients requiring an oxygen inspiratory fraction (FiO2) 2. Walked distance, perceived dyspnea, pulse oximetry, and inspiratory capacity at end of the tests as well as patients’ comfort were compared between the tests. Results: As compared to baseline, walked distance improved significantly more in HFNO than in the control test (by 61.1 ± 37.8 and 39.7 ± 43.8 m, respectively, p = 0.01). There were no significant differences between the tests in dyspnea, peripheral oxygen saturation, or inspiratory capacity, but HFNO test was appreciated as more comfortable. Conclusion: In patients with COPD and severe exercise limitation, HFNO delivered by a battery-supplied portable device was more effective in improving walking distance than usual oxygen supplementation.

The aim of this study was to test and validate a new hospital Mass Casualty Incident (MCI) training using MACSIM® (MAss Casualty SIMulation) system adapted to the specifications and MCI plan of a single hospital. The original MCI training format called MACSIM-PEMAF (Piano di Emergenza per il Massiccio Afflusso di Feriti, i.e., hospital disaster plan for massive influx of casualties) was developed for the Italian Society for Trauma and Emergency Surgery (SICUT) in 2016. It uses MACSIM®, a simulation tool for the training and assessment of healthcare professionals in MCI management. Between 2016 and 2018 the course was held several times at a university hospital in the Milan metropolitan area. The MACSIM® tool was used to reproduce different MCI scenarios with actual hospital resources. During the simulations, participants acted in their usual professional functions, testing both the local MCI plan as well as the individuals’ knowledge and skills. Course effectiveness was validated by a pre- and post-curse self-assessment questionnaire. MACSIM-PEMAF was tested over 7 courses, with a total of 258 participants. Pre- and post-course questionnaires showed a significant improvement for hospital staff in self-reported perceptions of knowledge and skills in MCI management. In total, on a 1–10 scale, all the staff increased their competencies from a value of 4.4 ± 2.5 to 7.5 ± 1.9 (p

In this paper we start illustrating our experience of multifocal chorangiomatosis with the newborn affected by massive umbilical vein thrombosis, disseminated intravascular coagulopathy and hydrops, going to a literature review of cases available.Our clinical case and the review of literature highlight how multifocal chorangiomatosis, within the three subgroups identified, is the rarer form with distinct placental features and the worst outcomes for neonates. No cases of multifocal chorangiomatosis have never been described prenatally and, for further studies, could be reasonable investigate the involvement of some growth factors like vascular endothelial growth factor and placental growth factor that could lead to a detection of a subgroup of patient at higher risk to manifest placental vascular lesions and the follow fetal and maternal complications.

Background and objective Through percutaneous approaches, hallux valgus corrections can be performed with minimal soft tissue injury, postoperative pain, and good cosmetic results. Bosch osteotomy and MICA (Minimally Invasive Chevron Akin) have been shown to be effective techniques for the correction of hallux valgus, although there are currently no publications comparing percutaneous techniques with each other. The aim of this work is to compare the radiological and functional results of both techniques. Materials and methods A retrospective, comparative study was carried out on patients with moderate hallux valgus. They were divided into 2 groups according to the percutaneous technique used: chevron osteotomy and Bosch osteotomy with screw fixation. The metatarsophalangeal, intermetatarsal, and distal articular veneer declination angles of the first metatarsal and the bone consolidation time were evaluated radiologically. The American Orthopaedic Foot and Ankle Surgery (AOFAS) scale was used for functional assessment. Complications were collected during the first year. Results Thirty-eight patients in each group were included for the study. In each of the groups, the radiological angles were compared preoperatively and at the end of the follow-up, showing statistically significant changes in the 3 variables considered; but no differences were obtained by comparing them with each other. The time of consolidation was also similar in both groups. As for the AOFAS scale, an improvement was obtained with both techniques, but the difference was not significant when comparing them. Conclusions Both Bosch and MICA techniques showed comparable results at the end of the monitoring. Further work is needed to determine the advantages of each in the immediate postoperative period.

This case report describes orthodontic treatment including both skeletal maxillary expansion and unilateral distalization by means of a single bone-borne appliance followed by clear aligner therapy in a young adult patient. A surgical guide was digitally designed and three-dimensionally printed to facilitate the placement of four miniscrews in the palatal vault. The miniscrews were fitted and the bone-borne appliance was delivered in a single clinical appointment. The postexpansion photographic records and models demonstrate the opening of the palatal median suture, the pure skeletal expansion, and the resolution of the left crossbite after 40 activations. Specifically, left molar Class I was obtained in about 5 months without any loss of anterior anchorage, and the subsequent aligner phase achieved all of the objectives established in the treatment plan. This case report shows clearly how careful digital planning of miniscrew insertion and the delivery of a pure bone-borne appliance in a single sitting enabled good clinical outcomes to be achieved in an acceptable timeframe, without side effects, even in a young adult patient.

Highlights • Pre workshop international survey on MPV • Best practice guidline on the provision of MPV in NMD's by reviewing and recommend the most appropriate monitoring, mode, settings and equipment required for MPV. • Best practice algorithm on MPV for daytime ventilatory support (see Figure 1 ).Figure 1Figure 1 shows the best practice algorithm for the initiation of mouthpiece ventilation (MPV) in the long-term setting. For each stage of the algorithm there is a description to assist in the provision of this service.Figure 1 • Future studies in MPV.

The eXtreme Lateral Interbody Fusion (XLIF) approach has gained increasing importance in the last decade. This multicentric retrospective cohort study aims to assess the incidence of major complications in XLIF procedures performed by experienced surgeons and any relationship between the years of experience in XLIF procedures and the surgeon’s rate of severe complications. Nine Italian members of the Society of Lateral Access Surgery (SOLAS) have taken part in this study. Each surgeon has declared how many major complications have been observed during his surgical experience and how they were managed. A major complication was defined as an injury that required reoperation, or as a complication, whose sequelae caused functional limitations to the patient after one year postoperatively. Each surgeon was finally asked about his years of experience in spine surgery and XLIF approach. Pearson correlation test was used to evaluate the association between the surgeon’s years of experience in XLIF and the rate of major complications; a p-value of last than 0.05 was considered significant. We observed 14 major complications in 1813 XLIF procedures, performed in 1526 patients. The major complications rate was 0.7722%. Ten complications out of fourteen needed a second surgery. Neither cardiac nor respiratory nor renal complications were observed. No significant correlation was found between the surgeon's years of experience in the XLIF procedure and the number of major complications observed. XLIF revealed a safe and reliable surgical procedure, with a very low rate of major complications, when performed by an expert spine surgeon.

Context The pathogenesis of nephrolithiasis in primary hyperparathyroidism (PHPT) remains to be elucidated. The latest guidelines suggest parathyroidectomy in patients with asymptomatic PHPT with hypercalciuria (> 400 mg/d) and increased stone risk profile. Objective The objective of this work is to evaluate the association of urinary stone risk factors and nephrolithiasis in patients with asymptomatic sporadic PHPT and its clinical relevance. Design A total of 157 consecutive patients with sporadic asymptomatic PHPT were evaluated by measurement of serum and 24-hour urinary parameters and kidney ultrasound. Results Urinary parameters were tested in the univariate analysis as continuous and categorical variables. Only hypercalciuria and hypomagnesuria were significantly associated with nephrolithiasis in the univariate and multivariate analysis adjusted for age, sex, body mass index, estimated glomerular filtration rate, parathyroid hormone, 25-hydroxyvitamin D, serum calcium, and urine volume (odds ratio, OR 2.14 [1.10-4.56]; P = .04; OR 3.06 [1.26-7.43]; P = .013, respectively). Hypomagnesuria remained associated with nephrolithiasis in the multivariate analysis (OR 6.09 [1.57-23.5], P = .009) even when the analysis was limited to patients without concomitant hypercalciuria. The urinary calcium/magnesium (Ca/Mg) ratio was also associated with nephrolithiasis (univariate OR 1.62 [1.27-2.08]; P = .001 and multivariate analysis OR 1.74 [1.25-2.42], P = .001). Hypomagnesuria and urinary Ca/Mg ratio had a better, but rather low, positive predictive value compared with hypercalciuria. Conclusions Hypomagnesuria and urinary Ca/Mg ratio are each associated with silent nephrolithiasis and have potential clinical utility as risk factors, besides hypercalciuria, for kidney stones in asymptomatic PHPT patients. The other urinary indices that have been commonly thought to be associated with kidney stones in PHPT are not supported by our results.

Uretero-pelvic junction obstruction is the most common cause of prenatal hydronephrosis. It can be intrinsic, extrinsic due to crossing vessel (CV) or mixed. This paper aims to present the surgical outcome in a single pediatric third-level center. A retrospective analysis of all children operated between 2011 and 2018 was conducted. Demographic information, pre-operative pelvic antero-posterior diameter (APD), intra-operative parameters, hospital stay and follow-up were considered. Re-do operations and success rate for Vascular Hitch (VH), open and laparoscopic pyeloplasties were recorded. 128 patients were included. The mean pre-operative APD was 30 mm. The etiology was intrinsic in 71.9%, extrinsic in 25.0% and mixed in 3.1%. The median age between intrinsic and extrinsic groups was statistically different. Thirty-one VH, 88 dismembered and 9 non-dismembered pyeloplasties were performed. The median hospital stay was 2 days for VH and 6 for pyeloplasties. The median hospital stay was statistically longer in open pyeloplasties compared to laparoscopic. The mean post-operative APD was 14 mm. The success rate after VH was 90.3%, after open pyeloplasties 97.9% and after mini-invasive pyeloplasties 91.8%. VH could be a good option in the treatment of hydronephrosis due to CV, laparoscopic pyeloplasties have equivalent success rate and shorter hospital stay than open pyeloplasties.

Background: Previous research has examined the relation between mental illness (MI) and perceptions of dangerousness, but less research has focused on its relation to perceived risk of criminality. Individuals with MI are perceived to be more dangerous than those without, and individuals with schizophrenia or substance abuse diagnoses are viewed as being more dangerous. Research also supports that race of individuals with MI plays an important role in the conceptualization and experience of stigma. Aims: The current study investigated the relation between MI, perceived criminality and race of diagnosed individuals. Method: Two hundred ninety participants were randomly assigned to read one of the four vignettes and answer a series of questions. The first three vignettes depicted someone with MI (schizophrenia, depression or alcohol dependency), while the fourth vignette served as a control. Participants were asked to indicate likelihood of committing a future crime, severity of the future crime and the person’s potential for rehabilitation. Levels of sympathy and trust, as well as perceived race of the person, were also measured. Results: Presence of MI was a significant predictor where MI elicited higher levels of perceived risk of criminality. The remaining predictor variables (type of MI, familiarity with MI and criminality and perceived race) were not significant predictors. Exploratory analyses revealed the schizophrenia and alcohol dependency conditions elicited higher levels of perceived severity of future crimes. Perceived MI severity and likelihood of rehabilitation were all significantly correlated with perceived risk of criminality. Conclusion: Presence of MI appears to be the most important in influencing participant attitudes about perceived risk of criminality, though type of MI may influence beliefs about severity of future crimes. The impact of race could not be examined but should be examined in future studies.

Background: Autologous haematopoietic stem cell transplantation (aHSCT) is a valuable option in aggressive relapsing–remitting multiple sclerosis (MS), but its efficacy in secondary progressive (SP)-MS is still controversial. Objective: Assessing efficacy of aHSCT in SP-MS by clinical-radiological outcomes. Methods: Open-label monocentric retrospective study enrolling consecutive SP-MS patients treated with BEAM-aHSCT in the period 1999–2016. Results: In total, 26 SP-MS patients with moderate–severe disability were included. Progression-free survival (PFS) at years 5 and 10 after aHSCT were, respectively, 42% and 30%. Out of 16 patients who worsened, only 6 patients (23% overall) maintained continuous disability accrual (CDA), whereas 10 patients stabilized following one single-step Expanded Disability Status Scale (EDSS) worsening. CDA-free survival was 74% at 5–10 years. No relapses or magnetic resonance imaging (MRI) activity were reported, thus no evidence of disease activity (NEDA)-3 corresponded to PFS. Annualized rate of brain atrophy (AR-BVL) normalized after 1 year in 55% of the cases analysed (12/22). Conclusion: BEAM-aHSCT halted CDA and normalized AR-BVL in most of the treated patients, inducing long-term remission of inflammatory activity at a median follow-up of 99 months (range 27–222). These data suggest that CDA might still be mainly driven by inflammation in a subgroup of SP-MS and could therefore be reversed by treatments. CDA should be analysed independently from any isolated disability worsening.

A 60-year-old male Caucasian, who was a smoker, was referred to the pulmonology clinic because of dyspnea. He also had bilateral arthralgia of the hands and wrists. The patient had a history of rheumatoid arthritis, which was being treated with immunosuppressive drugs. Chest radiography revealed right-sided pleural effusion; thus ultrasound-guided right thoracentesis was performed, resulting in extraction of 1300 mL of cloudy nonmalodorous pleural fluid. Microbiological and cytological analyses were unremarkable, whereas the chemical–physical examination revealed pseudochylothorax. The triglyceride concentration was low, no chylomicrons were detected, and the cholesterol concentration was high. Subsequent chest computed tomography (CT) demonstrated thickened parietal pleura on the right side with a small area of residual pleural effusion, together with right lower lobe segmental atelectasis. The patient underwent medical thoracoscopy, which showed soft yellow peel over the basal parietal pleura. Multiple biopsy specimens were obtained. Microbiology results for the pleural fluid and parietal pleura were negative. Histological examination of biopsy specimens revealed infiltration by inflammatory cells, multinucleated giant cells, and very few mesothelial cells, in a background of amorphous material. No malignant cells or granulomas were detected. The findings were consistent with rheumatoid pleurisy. The patient was started on a new treatment with a selective Janus kinase inhibitor, which led to progressive reduction of rheumatoid arthritis symptoms. At the follow-up, chest ultrasonography and CT showed significant reduction in pleural effusion and lung atelectasis. This chapter provides a comprehensive description of pseudochylothorax and addresses related topics, such as pleural fluid pH measurement and moderate sedation during medical thoracoscopy.

Scabies is a skin infestation from the Sarcoptes scabiei. It is considered a public health issue causing concern in developing countries and is one of the World Health Organization (WHO) Neglected Tropical Disease. Scabies skin lesions may cause severe itch and can be the portal of entry for opportunistic and pathogenic bacteria which can cause serious systemic infections. We report the case of a 3 year-old-boy with recurrent scabies infection presenting to the Emergency Department because of fever and refusal to walk. At medical examination he looked unwell, right thigh was extremely painful on palpation and blood test showed neutrophilic leucocytosis and significantly increased C reactive protein (CRP) and procalcitonin. Magnetic resonance imaging (MRI) showed an osteomyelitis of metaphysis and distal diaphysis of the right femur with associated subperiosteal purulent collection and concomitant pyomyositis and fasciitis of the distal right thigh. Blood cultures turned positive for Methicillin-Resistant Staphylococcus aureus. He received a long course of intravenous antibiotic therapy and his condition slowly improved. Follow-up femur X-ray showed a mixed pattern of erosion and sclerosis at meta-diaphyseal region and periosteal reaction at diaphyseal region. This case highlights the importance of early scabies diagnosis even in Western countries where poverty and household overcrowding are not matters of concern. Early diagnosis, timely begin of proper treatment and evidence of clinical resolution are important elements to prevent recurrence of infection and serious systemic superinfections even from multi-drug resistant bacteria. Clinical consequences from unrecognized disease or inadequate eradication are preventable.

Background: Second cancer is the leading cause of death in lymphoma survivors, with lung cancer representing the most common solid tumor. Limited information exists about the treatment and prognosis of second lung cancer following lymphoma. Herein, we evaluated the outcome and prognostic factors of Lung Cancer in Lymphoma Survivors (the LuCiLyS study) to improve the patient selection for lung cancer treatment. Methods: This is a retrospective multicentre study including consecutive patients treated for lymphoma disease that subsequently developed non-small cell lung cancer (NSCLC). Data regarding lymphoma including age, symptoms, histology, disease stage, treatment received and lymphoma status at the time of lung cancer diagnosis, and data on lung carcinoma as age, smoking history, latency from lymphoma, symptoms, histology, disease stage, treatment received, and survival were evaluated to identify the significant prognostic factors for overall survival. Results: Our study population included 164 patients, 145 of which underwent lung cancer resection. The median overall survival was 63 (range, 58-85) months, and the 5-year survival rate 54%. At univariable analysis no-active lymphoma (HR: 2.19; P=0.0152); early lymphoma stage (HR: 1.95; P=0.01); adenocarcinoma histology (HR: 0.59; P=0.0421); early lung cancer stage (HR: 3.18; P

Background The efficacy and safety of high flow nasal therapy (HFNT) in patients with acute hypercapnic exacerbation of chronic obstructive pulmonary disease (AECOPD) are unclear. Our aim was to evaluate the short-term effect of HFNT versus NIV in patients with mild-to-moderate AECOPD, with the hypothesis that HFNT is non-inferior to NIV on CO2 clearance after 2 h of treatment. Methods We performed a multicenter, non-inferiority randomized trial comparing HFNT and noninvasive ventilation (NIV) in nine centers in Italy. Patients were eligible if presented with mild-to-moderate AECOPD (arterial pH 7.25–7.35, PaCO2 ≥ 55 mmHg before ventilator support). Primary endpoint was the mean difference of PaCO2 from baseline to 2 h (non-inferiority margin 10 mmHg) in the per-protocol analysis. Main secondary endpoints were non-inferiority of HFNT to NIV in reducing PaCO2 at 6 h in the per-protocol and intention-to-treat analysis and rate of treatment changes. Results Seventy-nine patients were analyzed (80 patients randomized). Mean differences for PaCO2 reduction from baseline to 2 h were − 6.8 mmHg (± 8.7) in the HFNT and − 9.5 mmHg (± 8.5) in the NIV group (p = 0.404). By 6 h, 32% of patients (13 out of 40) in the HFNT group switched to NIV and one to invasive ventilation. HFNT was statistically non-inferior to NIV since the 95% confidence interval (CI) upper boundary of absolute difference in mean PaCO2 reduction did not reach the non-inferiority margin of 10 mmHg (absolute difference 2.7 mmHg; 1-sided 95% CI 6.1; p = 0.0003). Both treatments had a significant effect on PaCO2 reductions over time, and trends were similar between groups. Similar results were found in both per-protocol at 6 h and intention-to-treat analysis. Conclusions HFNT was statistically non-inferior to NIV as initial ventilatory support in decreasing PaCO2 after 2 h of treatment in patients with mild-to-moderate AECOPD, considering a non-inferiority margin of 10 mmHg. However, 32% of patients receiving HFNT required NIV by 6 h. Further trials with superiority design should evaluate efficacy toward stronger patient-related outcomes and safety of HFNT in AECOPD. Trial registration: The study was prospectively registered on December 12, 2017, in ClinicalTrials.gov (NCT03370666).

Objectives Few studies have analyzed factors associated with delirium subtypes. In this study, we investigate factors associated with subtypes of delirium only in patients with dementia to provide insights on the possible prevention and treatments. Design This is a cross-sectional study nested in the "Delirium Day" study, a nationwide Italian point-prevalence study. Setting and participants Older patients admitted to 205 acute and 92 rehabilitation hospital wards. Measures Delirium was evaluated with the 4-AT and the motor subtypes with the Delirium Motor Subtype Scale. Dementia was defined by the presence of a documented diagnosis in the medical records and/or prescription of acetylcholinesterase inhibitors or memantine prior to admission. Results Of the 1057 patients with dementia, 35% had delirium, with 25.6% hyperactive, 33.1% hypoactive, 34.5% mixed, and 6.7% nonmotor subtype. There were higher odds of having venous catheters in the hypoactive (OR 1.82, 95% CI 1.18-2.81) and mixed type of delirium (OR 2.23, CI 1.43-3.46), whereas higher odds of urinary catheters in the hypoactive (OR 2.91, CI 1.92-4.39), hyperactive (OR 1.99, CI 1.23-3.21), and mixed types of delirium (OR 2.05, CI 1.36-3.07). We found higher odds of antipsychotics both in the hyperactive (OR 2.87, CI 1.81-4.54) and mixed subtype (OR 1.84, CI 1.24-2.75), whereas higher odds of antibiotics was present only in the mixed subtype (OR 1.91, CI 1.26-2.87). Conclusions and implications In patients with dementia, the mixed delirium subtype is the most prevalent followed by the hypoactive, hyperactive, and nonmotor subtype. Motor subtypes of delirium may be triggered by clinical factors, including the use of venous and urinary catheters, and the use of antipsychotics. Future studies are necessary to provide further insights on the possible pathophysiology of delirium in patients with dementia and to address the optimization of the management of potential risk factors.

Uterine leiomyomas are a common finding in medical practice, but their frequency changes drastically when contextualized in a syndrome, as in the following case. A 50-year-old woman with a known Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome presented at our clinic with abdominal pain located in the lower quadrants and scarcely responsive to analgesic therapy. A twisted gynecological pelvic mass was diagnosed, and management for prompt resolution was adopted. Histologically the mass was described as a leiomyoma. The aim of the present study is to share our experience and to review the literature to compare different manifestation of the disease and different approach used in the various centers. The additional novelty of the paper is the immunohistochemical study we carried out on the leiomyoma that is contrasted with the current etiopathogenetic theories.

We explore home use of a portable bi-level ventilation device among patients with severe chronic obstructive pulmonary disease (COPD), and describe changes in the patients’ physical activity levels, perceived dyspnea, anxiety and depression, as well as their satisfaction with the device, after one month of use. Methods. Forty patients with severe COPD and exertional dyspnea were instructed to use VitaBreath® device (Philips, Respironics) during efforts or activities of daily living for 4weeks, and agreed to answer questionnaires on anxiety, depression, dyspnea and physical activity. Results. Twenty-six (65%) patients used the VitaBreath® device for four weeks, while 14 patients (35%) stopped early for various reasons. Among patients who completed the 4-week course, no differences in dyspnea and physical activity were observed between baseline and follow-up (p-values 0.41 and 0.19, respectively). Thirteen (50%) and 15 (57%) patients experienced reduced anxiety and depression, respectively. Patients with greater functional impairment and less autonomy in activities of daily living tended to view the device more positively. Conclusion. Home use of portable bi-level positive-pressure ventilation devices by patients with COPD may alleviate disease-related anxiety and depression, particularly in more severe cases of COPD. Future portable device design should feature adjustable inspiratory/expiratory pressures.

Objectives During severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, dramatic endothelial cell damage with pulmonary microvascular thrombosis have been was hypothesized to occur. The aim was to assess whether pulmonary vascular thrombosis (PVT) is due to recurrent thromboembolism from peripheral deep vein thrombosis or to local inflammatory endothelial damage, with a superimposed thrombotic late complication. Design Observational study. Setting Medical and intensive care unit wards of a teaching hospital. Participants The authors report a subset of patients included in a prospective institutional study (CovidBiob study) with clinical suspicion of pulmonary vascular thromboembolism. Interventions Computed tomography pulmonary angiography and evaluation of laboratory markers and coagulation profile. Measurements and Main Results Twenty-eight of 55 (50.9%) patients showed PVT, with a median time interval from symptom onset of 17.5 days. Simultaneous multiple PVTs were identified in 22 patients, with bilateral involvement in 16, mostly affecting segmental/subsegmental pulmonary artery branches (67.8% and 96.4%). Patients with PVT had significantly higher ground glass opacity areas (31.7% [22.9-41] v 17.8% [10.8-22.1], p < 0.001) compared with those without PVT. Remarkably, in all 28 patients, ground glass opacities areas and PVT had an almost perfect spatial overlap. D-dimer level at hospital admission was predictive of PVT. Conclusions The findings identified a specific radiologic pattern of coronavirus disease 2019 (COVID-19) pneumonia with a unique spatial distribution of PVT overlapping areas of ground-glass opacities. These findings supported the hypothesis of a pathogenetic relationship between COVID-19 lung inflammation and PVT and challenged the previous definition of pulmonary embolism associated with COVID-19 pneumonia., Graphical abstract Computed Tomography Pulmonary Angiography (CTPA) imaging demonstrating, in three different clinical scenarios, eventual filling defects in branches of the pulmonary arteries (white arrows) and their spatial distribution according to the corresponding ventilation maps (white asterisks indicate normal lung parenchyma). In (a) [non COVID-19 pneumonia] and (c) [non COVID-19 ARDS] filling defects are electively found in the branches of the pulmonary arteries accountable for the vascularization of healthy lung segments. On the contrary, in (b) [COVID-19 pneumonia] there is an almost perfect topographical overlap between filling defects distribution and pneumonia extent.Image, graphical abstract

Background: Assessment of intrinsic dynamic positive end-expiratory pressure (PEEPi,dyn) may be clinically important in stable patients with chronic obstructive pulmonary disease (COPD), but epidemiological data are scant. Objectives: The aim of our study was (i) to assess the PEEPi,dyn in a large population of stable patients with COPD and (ii) to evaluate the correlations with some noninvasive measurements routinely assessed. Method: Retrospective analysis of lung mechanics, dynamic volumes, arterial blood gases, dyspnoea by means of the Medical Research Council (MRC) scale, the COPD Assessment Test score, and maximal inspiratory/expiratory pressures in 87 hypercapnic and 62 normocapnic patients. Results: The mean PEEPi,dyn was significantly higher in hypercapnic than normocapnic patients (2.8 ± 2.2 vs. 1.9 ± 1.6 cm H2O, respectively, p = 0.0094). PEEPi,dyn did not differ according to Global Initiative for Chronic Obstructive Lung Disease stage, MRC score, or use or not of long-term oxygen therapy. There were significant although weak correlations between PEEPi,dyn and airway obstruction, hyperinflation, respiratory muscle function, arterial CO2 tension, and number of exacerbations/year. The transdiaphragmatic pressure was the strongest variable associated to PEEPi,dyn (R = 0.5713, p = 0.001). Conclusion: In stable patients with COPD, PEEPi,dyn is higher in hypercapnic patients and weakly correlated to noninvasive measures of lung and respiratory muscle function.

OBJECTIVE Neutrophil extracellular traps (NETs) are extracellular lattices composed of nucleic material bound to neutrophil granule proteins. NETs may play pathogenic roles in the development and severity of autoimmune diseases such as systemic lupus erythematosus (SLE), at least in part, through induction of type I interferon (IFN) responses via externalization of oxidized immunostimulatory DNA. A distinct subset of SLE proinflammatory neutrophils (low-density granulocytes [LDGs]) displays enhanced ability to form proinflammatory NETs that damage the vasculature. We undertook this study to assess whether NET-bound RNA can contribute to inflammatory responses in endothelial cells (ECs) and the pathways that mediate this effect. METHODS Expression of newly synthesized and total RNA was quantified in NETs from healthy controls and lupus patients. The ability of ECs to take up NET-bound RNA and downstream induction of type I IFN responses were quantified. RNAs present in NETs were sequenced and specific small RNAs were tested for induction of endothelial type I IFN pathways. RESULTS NETs extruded RNA that was internalized by ECs, and this was enhanced when NET-bound nucleic acids were oxidized, particularly in lupus LDG-derived NETs. Internalization of NET-bound RNA by ECs was dependent on endosomal Toll-like receptors (TLRs) and the actin cytoskeleton and induced type I IFN-stimulated genes (ISGs). This ISG induction was dependent on NET-associated microRNA let-7b, a small RNA expressed at higher levels in LDG-derived NETs, which acted as a TLR-7 agonist. CONCLUSION These findings highlight underappreciated roles for small RNAs externalized in NETs in the induction of proinflammatory responses in vascular cells, with implications for lupus vasculopathy.

ObjectivesThe steroid hormone vitamin D has roles in immunomodulation and bone health. Insufficiency is associated with susceptibility to respiratory infections. We report 25-hydroxy vitamin D (25(OH)D) measurements in hospitalised people with COVID-19 and influenza A and in survivors of critical illness to test the hypotheses that vitamin D insufficiency scales with illness severity and persists in survivors.DesignCross-sectional study.Setting and participantsPlasma was obtained from 295 hospitalised people with COVID-19 (International Severe Acute Respiratory and emerging Infections Consortium (ISARIC)/WHO Clinical Characterization Protocol for Severe Emerging Infections UK study), 93 with influenza A (Mechanisms of Severe Acute Influenza Consortium (MOSAIC) study, during the 2009–2010 H1N1 pandemic) and 139 survivors of non-selected critical illness (prior to the COVID-19 pandemic). Total 25(OH)D was measured by liquid chromatography-tandem mass spectrometry. Free 25(OH)D was measured by ELISA in COVID-19 samples.Outcome measuresReceipt of invasive mechanical ventilation (IMV) and in-hospital mortality.ResultsVitamin D insufficiency (total 25(OH)D 25–50 nmol/L) and deficiency (ConclusionsVitamin D deficiency/insufficiency was present in majority of hospitalised patients with COVID-19 or influenza A and correlated with severity and persisted in critical illness survivors at concentrations expected to disrupt bone metabolism. These findings support early supplementation trials to determine if insufficiency is causal in progression to severe disease, and investigation of longer-term bone health outcomes.

INTRODUCTION The Joint United Nations Programme on HIV/AIDS (UNAIDS) projections of paediatric HIV prevalence and deaths rely on the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium for mortality estimates among children living with HIV (CHIV) receiving antiretroviral therapy (ART). Previous estimates, based on data through 2014, may no longer be accurate due to expanded paediatric HIV care and treatment eligibility, and the possibility of unreported deaths in CHIV considered lost to follow-up (LTFU). We therefore estimated all-cause mortality and its trends in CHIV (

BackgroundCOVID-19 is a multi-system disease and patients who survive may experience in-hospital complications. These complications are likely to have important short and long-term consequences for patients, healthcare utilisation, healthcare system preparedness, and society amidst the ongoing COVID-19 pandemic. Our aim was to characterise the extent and impact of COVID-19 complications, particularly in those who survive using the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) WHO Clinical Characterisation Protocol UK (CCP-UK).MethodsA multicentre, prospective cohort study in 302 UK healthcare facilities of adults hospitalised with COVID-19 between 17th January and 4th August 2020. Complications were defined as organ specific diagnoses occurring alone or in addition to any hallmarks of COVID-19 illness. Outcomes included death, critical care use, and ability to self-care at hospital discharge. We used multilevel logistic regression and survival models to explore associations between these outcomes and in-hospital complications, age, and pre-existing comorbidities.ResultsOf patients admitted to hospital for management of COVID-19, 49.7% (36 367/73 197) experienced at least one complication. The mean age of our cohort was 71.1 years old (SD 18.7), included more males (56.0%, 41 025/73 ) with 81.0% (59 289/73 197) of patients having at least one comorbidity. Males over 60 were most likely to experience a complication (60 y and over, 54.5% [16 579/30 416] in males and 48.2% [11 707/24 288] in females; Under 60 y, 48.8% [5179/10 609] in males, 36.6% [2814/7689] in females). Renal (24.3%, 17 752/73 197), complex respiratory 18.4% (13 486/73 197), and systemic (16.3%, 11 895/73 197) complications were most frequent. Cardiovascular (12.3%, 8973/73 197), neurological (4.3%, 3115/73 197), and gastrointestinal/liver (0.8%, 7901/73 197) complications were also reported. The presence of any complication was associated with significantly worse survival (adjusted HR 1.74, 95% CI 1.64 to 1.84) and increased admission to critical care (adjusted OR 7.25, 95% CI 6.83 to 7.69). Reduced ability to self-care at discharge was significantly greater in patients who experienced a complication (adjusted OR 2.42, 95% CI 2.31 to 2.54) and was greatest in those who experienced neurological complications (adjusted OR 4.39, 95% CI 3.95 to 4.89). ConclusionsComplications and worse functional outcomes in patients admitted to hospital with COVID-19 are high, even in young, previously healthy individuals. Acute complications are associated with reduced ability to self-care at discharge, with neurological complications being associated with the worst functional outcomes. COVID-19 complications are likely to cause significant strain on health and social care in the coming years. These data will help in the design and provision of services aimed at the post-hospitalisation care of patients with COVID-19.

ObjectivesIn lupus nephritis the pathological diagnosis from tissue retrieved during kidney biopsy drives treatment and management. Despite recent approval of new drugs, complete remission rates remain well under aspirational levels, necessitating identification of new therapeutic targets by greater dissection of the pathways to tissue inflammation and injury. This study assessed the safety of kidney biopsies in patients with SLE enrolled in the Accelerating Medicines Partnership, a consortium formed to molecularly deconstruct nephritis.Methods475 patients with SLE across 15 clinical sites in the USA consented to obtain tissue for research purposes during a clinically indicated kidney biopsy. Adverse events (AEs) were documented for 30 days following the procedure and were determined to be related or unrelated by all site investigators. Serious AEs were defined according to the National Institutes of Health reporting guidelines.Results34 patients (7.2%) experienced a procedure-related AE: 30 with haematoma, 2 with jets, 1 with pain and 1 with an arteriovenous fistula. Eighteen (3.8%) experienced a serious AE requiring hospitalisation; four patients (0.8%) required a blood transfusion related to the kidney biopsy. At one site where the number of cores retrieved during the biopsy was recorded, the mean was 3.4 for those who experienced a related AE (n=9) and 3.07 for those who did not experience any AE (n=140). All related AEs resolved.ConclusionsProcurement of research tissue should be considered feasible, accompanied by a complication risk likely no greater than that incurred for standard clinical purposes. In the quest for targeted treatments personalised based on molecular findings, enhanced diagnostics beyond histology will likely be required.

Background and objectives: In patients with kidney failure due to IgA nephropathy, IgA deposits can recur in a subsequent kidney transplant. The incidence, effect, and risk factors of IgA nephropathy recurrence is unclear, because most studies have been single center and sample sizes are relatively small.Design, setting, participants, & measurements: We performed a multicenter, international, retrospective study to determine the incidence, risk factors, and treatment response of recurrent IgA nephropathy after kidney transplantation. Data were collected from all consecutive patients with biopsy-proven IgA nephropathy transplanted between 2005 and 2015, across 16 “The Post-Transplant Glomerular Disease” study centers in Europe, North America, and South America.Results: Out of 504 transplant recipients with IgA nephropathy, recurrent IgA deposits were identified by kidney biopsy in 82 patients; cumulative incidence of recurrence was 23% at 15 years (95% confidence interval, 14 to 34). Multivariable Cox regression revealed a higher risk for recurrence of IgA deposits in patients with a pre-emptive kidney transplant (hazard ratio, 3.45; 95% confidence interval, 1.31 to 9.17) and in patients with preformed donorspecific antibodies (hazardratio, 2.59; 95%confidence interval, 1.09 to 6.19).Afterkidneytransplantation,development of de novo donor-specific antibodies was associated with subsequent higher risk of recurrence of IgA nephropathy (hazard ratio, 6.65; 95% confidence interval, 3.33 to 13.27). Immunosuppressive regimen was not associated with recurrent IgA nephropathy in multivariable analysis, including steroid use. Graft loss was higher in patients with recurrence of IgA nephropathy compared with patients without (hazard ratio, 3.69; 95% confidence interval, 2.04 to 6.66), resulting in 32% (95% confidence interval, 50 to 82) graft loss at 8 years after diagnosis of recurrence.Conclusions: In our international cohort, cumulative risk of IgA nephropathy recurrence increased after transplant and was associated with a 3.7-fold greater risk of graft loss.

INTRODUCTION: Identification and retention of HIV-positive children in HIV services is essential to ensure optimal health outcomes. This systematic review and meta-analysis examines the magnitude of attrition (loss to follow-up [LTFU] and death) of HIV-positive children from HIV services in low- and middle-income countries (LMICs). METHODS: We performed a comprehensive multi-database search of original studies reporting retention/attrition data for HIV-positive children in LMICs through April 2016. Outcomes included LTFU, death, and overall attrition (LTFU + death) at intervals up to 60 months of follow-up. At least two authors determined study eligibility, performed data extraction, and made quality assessments. We used random effects meta-analytic methods to aggregate effect sizes and perform meta-regression analyses. RESULTS: We identified 3,040 unique studies; 91 met eligibility criteria and were included in the analysis. This represents 147,129 HIV-positive children; most were from Africa (83%). LTFU definitions varied widely, with significant variability in outcomes across studies. Most attrition occurred in the first six months of follow-up, increasing to 23% by 36 months. HIV-positive children receiving antiretroviral therapy (ART) had significantly better retention in care than those not on ART. Studies that performed case-finding/tracing for those LTFU had better retention in care up to 24 months of follow-up. CONCLUSIONS: These findings underscore the high attrition of children from HIV services in LMICs. Early ART initiation and decentralized patient support services (e.g., tracing for those LTFU) have potential to improve retention in care. Implementation research and resources are urgently needed to improve retention among this vulnerable population. Registration of protocol: PROSPERO # CRD42016034180

Excessive daytime sleepiness (EDS) can be caused by insufficient sleep but is also a manifestation of medical or sleep disorders and a side effect of medications. It impacts quality of life and creates safety concerns in the home, at work, and on the roads. Screening questionnaires can be used to estimate EDS, but further evaluation is necessary. EDS is a common symptom of both narcolepsy and obstructive sleep apnea (OSA). Polysomnography and multiple sleep latency testing are used to diagnose these disorders. However, isolating the primary etiology of EDS can be challenging and may be multifactorial. Untreated OSA can show polysomnographic findings that are similar to narcolepsy. The effects of sleep deprivation and certain medications can also affect the polysomnographic results. These challenges can lead to misdiagnosis. In addition, narcolepsy and OSA can occur as comorbid disorders. If EDS persists despite adequate treatment for either disorder, a comorbid diagnosis should be sought. Thus, despite advances in clinical practice, appropriate management of these patients can be challenging. This review is focused on EDS due to OSA and narcolepsy and addresses some of the challenges with managing this patient population.

BACKGROUND Globally, tuberculosis (TB) remains a serious cause of morbidity and mortality for children. Mozambique is 1 of 30 high TB and TB/HIV burden countries. This study aimed to assess treatment outcomes of childhood TB in Chokwe District, Mozambique. METHODS A retrospective cohort study of children

A kidney-transplanted patient, unvaccinated against yellow fever (YF), developed high fever, progressed rapidly to hepatic insufficiency and coma, and died 8 days later. Real-time polymarase chain reaction for YF virus collected on the seventh day of symptoms was positive. Autopsy showed disseminated infection and midzonal hepatitis with apoptotic hepatocytes and minimal inflammatory reaction.

Objective Autoreactive IgE antibodies have been implicated in the pathogenesis of systemic lupus erythematosus (SLE). We hypothesize that omalizumab, a monoclonal antibody binding IgE, may improve SLE activity by reducing type I interferon (IFN) production by hampering plasmacytoid dendritic cells and basophil activation. This study was undertaken to assess the safety, tolerability, and clinical efficacy of omalizumab in mild to moderate SLE. Methods Sixteen subjects with SLE and a Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score of ≥4 and elevated autoreactive IgE antibody levels were randomized to receive omalizumab or placebo (2:1) for 16 weeks, followed by 16 weeks of open-label treatment and a 4-week washout period. The SLEDAI-2K score, British Isles Lupus Assessment Group index (BILAG 2004) score, and physician's global assessment of disease activity were recorded at each visit. The type I IFN-induced gene signature was determined using quantitative polymerase chain reaction. Results Omalizumab was well tolerated with no allergic reactions, and mostly mild adverse events comparable to those experienced with placebo treatment. SLEDAI-2K scores improved in the omalizumab group compared to the placebo group at week 16 (P = 0.038), as well as during the open-label phase in subjects initially receiving placebo (P = 0.02). No worsening in BILAG scores or the physician's global assessment was detected. There was a trend toward a reduction in IFN gene signature in subjects treated with omalizumab (P = 0.11), especially in subjects with a high baseline IFN signature (P = 0.052). Conclusion Our findings indicate that omalizumab is well tolerated in SLE and is associated with improvement in disease activity. Larger randomized clinical trials will be needed to assess the efficacy of omalizumab in patients with SLE.

BACKGROUND: Studies of patients admitted to hospital with COVID-19 have found varying mortality outcomes associated with underlying respiratory conditions and inhaled corticosteroid use. Using data from a national, multicentre, prospective cohort, we aimed to characterise people with COVID-19 admitted to hospital with underlying respiratory disease, assess the level of care received, measure in-hospital mortality, and examine the effect of inhaled corticosteroid use. METHODS: We analysed data from the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) WHO Clinical Characterisation Protocol UK (CCP-UK) study. All patients admitted to hospital with COVID-19 across England, Scotland, and Wales between Jan 17 and Aug 3, 2020, were eligible for inclusion in this analysis. Patients with asthma, chronic pulmonary disease, or both, were identified and stratified by age ( FINDINGS: 75 463 patients from 258 participating health-care facilities were included in this analysis: 860 patients younger than 16 years (74 [8·6%] with asthma), 8950 patients aged 16-49 years (1867 [20·9%] with asthma), and 65 653 patients aged 50 years and older (5918 [9·0%] with asthma, 10 266 [15·6%] with chronic pulmonary disease, and 2071 [3·2%] with both asthma and chronic pulmonary disease). Patients with asthma were significantly more likely than those without asthma to receive critical care (patients aged 16-49 years: adjusted odds ratio [OR] 1·20 [95% CI 1·05-1·37]; p=0·0080; patients aged ≥50 years: adjusted OR 1·17 [1·08-1·27]; p INTERPRETATION: Underlying respiratory conditions are common in patients admitted to hospital with COVID-19. Regardless of the severity of symptoms at admission and comorbidities, patients with asthma were more likely, and those with chronic pulmonary disease less likely, to receive critical care than patients without an underlying respiratory condition. In patients aged 16 years and older, severe asthma was associated with increased mortality compared to non-severe asthma. In patients aged 50 years and older, inhaled corticosteroid use in those with asthma was associated with lower mortality than in patients without an underlying respiratory condition; patients with chronic pulmonary disease had significantly increased mortality compared to those with no underlying respiratory condition, regardless of inhaled corticosteroid use. Our results suggest that the use of inhaled corticosteroids, within 2 weeks of admission, improves survival for patients aged 50 years and older with asthma, but not for those with chronic pulmonary disease. FUNDING: National Institute for Health Research, Medical Research Council, NIHR Health Protection Research Units in Emerging and Zoonotic Infections at the University of Liverpool and in Respiratory Infections at Imperial College London in partnership with Public Health England.

Background Anxious symptoms have a negative impact on different aspects of the elderly’s quality of life, ranging from the adoption of unhealthy lifestyle behaviours to an increased functional impairment and a greater physical disability. Different brief assessment instruments have been developed as efficacy measures of geriatric anxiety in order to overcome psychometric weaknesses of its long form. Among these, the 10-item Geriatric Anxiety Scale (GAS-10) showed strong psychometric properties in community-dwelling samples. However, its diagnostic accuracy is still unexplored, as well as its discriminative power in clinical samples. Methods In the present study, we explored the psychometric performance of the GAS-10 in the elderly through Item Response Theory in a sample of 1200 Italian community-dwelling middle-aged and elderly adults (53.8% males, mean age = 65.21 ± 9.19 years). Concurrent validity, as well as diagnostic accuracy, was examined in a non-clinical sample (N = 229; 46.72% males) and clinical sample composed of 35 elderly outpatients (74.28% females) with Generalized Anxiety Disorder (GAD). Results The GAS-10 displayed good internal construct validity, with unidimensional structure and no local dependency, good accuracy, and no signs of Differential Item Functioning (DIF) or measurement bias due to gender, but negligible due to the age. Differences in concurrent validity and diagnostic accuracy among the long form version of the GAS and the GAS-10 were not found significant. The GAS-10 may be more useful than the longer versions in many clinical and research applications, when time constraints or fatigue are issues. Conclusion Using the ROC curve, the GAS-10 showed good discriminant validity in categorizing outpatients with GAD disorder, and high anxiety symptoms as measured by the GAS-SF cut-off. The stable cut-off point provided could enhance the clinical usefulness of the GAS-10, which seems to be a promising valid and reliable tool for maximize diagnostic accuracy of geriatric anxiety symptoms.

Background Early in the pandemic it was suggested that pre-existing use of non-steroidal anti-inflammatory drugs (NSAIDs) could lead to increased disease severity in patients with COVID-19. NSAIDs are an important analgesic, particularly in those with rheumatological disease, and are widely available to the general public without prescription. Evidence from community studies, administrative data, and small studies of hospitalised patients suggest NSAIDs are not associated with poorer COVID-19 outcomes. We aimed to characterise the safety of NSAIDs and identify whether pre-existing NSAID use was associated with increased severity of COVID-19 disease. Methods This prospective, multicentre cohort study included patients of any age admitted to hospital with a confirmed or highly suspected SARS-CoV-2 infection leading to COVID-19 between Jan 17 and Aug 10, 2020. The primary outcome was in-hospital mortality, and secondary outcomes were disease severity at presentation, admission to critical care, receipt of invasive ventilation, receipt of non-invasive ventilation, use of supplementary oxygen, and acute kidney injury. NSAID use was required to be within the 2 weeks before hospital admission. We used logistic regression to estimate the effects of NSAIDs and adjust for confounding variables. We used propensity score matching to further estimate effects of NSAIDS while accounting for covariate differences in populations. Results Between Jan 17 and Aug 10, 2020, we enrolled 78 674 patients across 255 health-care facilities in England, Scotland, and Wales. 72 179 patients had death outcomes available for matching; 40 406 (56·2%) of 71 915 were men, 31 509 (43·8%) were women. In this cohort, 4211 (5·8%) patients were recorded as taking systemic NSAIDs before admission to hospital. Following propensity score matching, balanced groups of NSAIDs users and NSAIDs non-users were obtained (4205 patients in each group). At hospital admission, we observed no significant differences in severity between exposure groups. After adjusting for explanatory variables, NSAID use was not associated with worse in-hospital mortality (matched OR 0·95, 95% CI 0·84–1·07; p=0·35), critical care admission (1·01, 0·87–1·17; p=0·89), requirement for invasive ventilation (0·96, 0·80–1·17; p=0·69), requirement for non-invasive ventilation (1·12, 0·96–1·32; p=0·14), requirement for oxygen (1·00, 0·89–1·12; p=0·97), or occurrence of acute kidney injury (1·08, 0·92–1·26; p=0·33). Interpretation NSAID use is not associated with higher mortality or increased severity of COVID-19. Policy makers should consider reviewing issued advice around NSAID prescribing and COVID-19 severity. Funding National Institute for Health Research and Medical Research Council.