The Covid-19 pandemic has disrupted health care systems all over the world. Elective surgical procedures have been postponed and/or cancelled. Consensus is, therefore, required related to the factors that need to be in place before elective surgery, including hip and knee replacement surgery, which is restarted. Entirely new pathways and protocols need to be worked out.A panel of experts from the European Hip Society and European Knee Association have agreed to a consensus statement on how to reintroduce elective arthroplasty surgery safely. The recommendations are based on the best available evidence and have been validated in a separate survey.The guidelines are based on five themes: modification and/or reorganisation of hospital wards. Restrictions on orthopaedic wards and in operation suite(s). Additional disinfection of the environment. The role of ultra-clean operation theatres. Personal protective equipment enhancement.Apart from the following national and local guidance, protocols need to be put in place in the patient pathway for primary arthroplasty to allow for a safe return. In recent months, the SARS-CoV-2 pandemic has evolved rapidly in Europe, disrupting the personal, social, economic and professional lives of health professionals on a large scale. The overall goal of most governments in Europe has been to flatten the curve of infected SARS-CoV-2 patients and prevent a collapse of national health systems. The April 2020 SARS-CoV-2 survey completed by EHS and EKA members in Europe has confirmed the impact of SARS-CoV-2. This pandemic has resulted in a tremendous reduction in primary hip and knee arthroplasties performed. Consensus is required about the factors that need to be in place before restarting such procedures.Delaying hip and knee arthroplasty in patients with severe osteoarthritis (OA) may adversely affect their final outcome. It lead to increased opioid use. It is associated with lower clinical results and increased readmission rates after the index procedure. Moreover, when access to hip and knee arthroplasty is limited, as it is now in the wake of the SARS-CoV-2 virus control measures, the direct and indirect costs for health care and social systems are enormous. Many patients suffering from OA have to prolong their absence from work, request temporary unemployment benefits, and/or burden the public welfare system.A new phase is now starting in most European countries, where restarting elective hip and knee arthroplasty surgery is being planned. The existing guidelines are not robust enough and therefore, improvement is much needed. The aim of this report is to describe the optimal trajectory for restarting elective hip and knee arthroplasty surgery. As a result, the European Hip Society (EHS) and the European Knee Association (EKA) worked with a panel of experts and have produced a thorough consensus report on how safe reintroduction of elective arthroplasty surgery can be achieved. The recommendations are based on the most recent available evidence and have been validated in a survey by world-wide arthroplasty surgeons.A panel of experts were tasked with reviewing the evidence available for managing primary elective hip and knee arthroplasty following the SARS-CoV-2 pandemic were asked:When should elective hip and knee arthroplasty be resumed?Are new triage/patient selection criteria needed for hip and knee arthroplasty patients once elective surgery is resumes?What are the priority indications for elective adult hip and knee reconstruction?What is the role of outpatient hip and knee arthroplasty/enhanced recovery protocols in light of the SARS-CoV-2 pandemic?What is the impact of delaying hip and knee arthroplasty for the patients themselves and for society?What is the appropriate preoperative clinical and laboratory screening and timeline for patients?Is preoperative tracking of patients, staff and relatives necessary?Should only patients who also consent to regional/spinal anaesthesia be selected as candidates?If spinal anaesthesia does not occur, should the operation be cancelled?Should spinal anaesthesia be routine?4.If the SARS-CoV-2 tests are positive, how long should the hip or knee arthroplasty surgery be postponed?5.What kind of back-up plan is needed to guarantee quality care and patient safety in this pandemic situation?Modification or reorganization of hospital wards ?Separation of elective and trauma orthopaedic surgery ?Is there a need for:Should relatives/visitors or other supportive personnel be allowed onto the orthopaedic wards and operating suite?Is there a need for extra disinfecting environmental procedures in between operations?What roles do ultra-clean operating theatres, orthopaedic exhaust suits and ultraviolet light systems play in both the wards/beds and the theatre?What are the guidelines for personal protective equipment (PPE), in terms of availability and instructions regarding its use and what to wear in relation to the patient’s position in the perioperative chain?Since the impact on mind and body during joint arthroplasty is significant, do the patients may have lower immunity and be more vulnerable to SARS-CoV-2 infection?Should a shelter-in-place post-operative period, home care, community nurses or informal care be organised?Consider telemedicineConsider a new approach in wound closure technique in the setting of the SARS-CoV-2 pandemicShould face-to-face contact for the orthopaedic follow-up and physical therapy guidance be avoided?What is the advice for patients who develop SARS-CoV-2 symptoms?Are special adjustments needed for post-op SARS-CoV-2 prophylaxis?The panel then agreed a statement that answered each question, along with reporting the rationale for the recommendation.When should elective hip and knee arthroplasty be resumed?Statement Elective hip and knee arthroplasty can be resumed when appropriate prerequisites concerning facilities, workforce, testing, supplies are met, and approval of local health authorities is obtained. Facilities in areas with low, or relatively low and stable incidence of SARS-CoV-2, can be allowed to provide care for patients needing non-emergency, non-SARS-CoV-2 healthcare.Rationale The US Centers for Disease Control advise that the following gating criteria to be met before reopening facilities to provide non-emergency health care [Downward trajectory of cases with influenza-like and COVID symptoms within the last 14 days.Downward trajectory of documented cases and positive tests as a percentage of total tests within 14 daysHospitals have treated all COVID cases without crisis careRobust testing programme in place for at-risk health care workers, including emerging antibody testinglth care :DownwardDepending on the country and the locations involved, some hospitals may be overburdened, while non-COVID care facilities may be inactive. The US Centers for Medicare & Medicaid Services (CMS), in their ‘Recommendations for Re-opening Facilities to Provide Non-emergent Non-SARS-CoV-2 Health Care’ , advise Timing of resumption: There must be a sustained reduction in the rate of new SARS-CoV-2 cases in the relevant geographic area for at least 14 days before the resumption of elective surgical procedures , 32, 43Any resumption should be authorised by the appropriate municipal, county and state health authoritiesFacilities in the state are safely able to treat all patients requiring hospitalisation without resorting to crisis standards of careThe facility needs to have an appropriate number of ICU and non-ICU beds, PPE items, ventilators, medications, anaesthetics and medical surgical supplies to cope with a second wave of pandemicAppropriate decontamination of the hospital and necessary equipment has occurredThe facility needs to have an adequate number of trained and educated staff available to handle the planned surgical procedures, patient population and facility resources. Given the known evidence supporting health care worker fatigue and the impact of stress, the facilities should be able to perform planned procedures to organise two different pathways inside the structure for SARS-CoV-2 and non-COVID patients without compromising patient safety or staff well-beingIdeally, all the staff who will be involved in patient care have been tested for SARS-CoV-2 (RT-PCR) on a regular basis and/or undergone serum antibody testing for the virusThe facility should be able and to have two different, separated surgical blocks for the two categories of patientsThe International Consensus Group (ICM) and the AAHKS Research Committee advise that the following prerequisites be met before the resumption of elective procedures :Timing oExposure-to-infection status unknown. Should get a COVID RT-PCR test 48–72 h before surgery Exposed but asymptomatic. Should get a COVID RT-PCR test, immune/serology test  and eventually a lung CT scan before surgeryRecovered from infection and possibly adequately immune. Should get an immune/serology test  before surgeryPresumed to be infected . Should get a repeated COVID RT-PCR test, an immune/serology test  and eventually a lung CT scan before considering any surgeriesInfected . Delay any elective surgery for 6 weeks and then should get an immune/serology test  before surgeryInfected with co-morbidity . Delay any elective surgery until full recovery (for at least 2 months) and then should get an immune/serology test 2.Are new triage/patient selection criteria needed for hip and knee arthroplasty patients once elective surgery is resumes?Statement Increased demand for hip and knee arthroplasty, coupled with limited hospital resources, will force surgeons to select which patients should receive hip and knee arthroplasties sooner than others. This will entail employing objective, transparent criteria in prioritising patient selection to identify the patients most in need who also have lower risk factors for disease transmission and post-operative complications.Rationale An increased demand for hip and knee arthroplasty care is foreseen once elective procedures are resumed in Europe, where public health systems are the major health care payers. Conversely, in countries where health insurance is linked to employment and private insurance companies are the main payers (e.g. the USA), demand may decline due to unemployment/underemployment or people’s need to continue working for economic reasons despite their symptoms. Several guidelines are available for prioritising patients undergoing elective surgery.ESSKA Guidelines also focus on the SARS-CoV-2 exposure status of the patient described by Fineberg and recommend elective surgery only in the first three of the following six categories , 25:ExpoProcedural factors Disease factors Patient factors The MeNTS Score   is a scoThe score can range from 21 to 105, with higher scores being associated with poorer perioperative patient outcomes, increased risk of SARS-CoV-2 transmission to the health care team, and/or increased hospital resource use. Although there is no threshold for safe elective surgery, the hospitals can adjust their thresholds depending on resources.The International Consensus Group (ICM) and the AAHKS Research Committee  recommen3.What are the priority indications for elective adult hip and knee reconstruction?Statement There is universal agreement regarding the indications for urgent hip and knee arthroplasty procedures, such as femoral neck fractures, periprosthetic fractures, dislocations and acute infection, even in the setting of the SARS-CoV-2 pandemic. However, priority indications for non-emergency procedures in primary and revision hip and knee arthroplasty are lacking and should be clarified.ESSKA guidelines  advise gAcute fractures requiring hip and knee arthroplasty First-stage explantations for acute PJI (periprosthetic joint infection)Amputation in cases of failed arthroplastyOne-stage revision for acute PJIRevision surgery required for massively failed arthroplasty: imminent fracture, massive osteolysis at risk of implant migration, implant breakage, pending fractures because of osteolysis or instability, severe adverse reaction to metal debris (ALTR or ARMD)Osteonecrosis with joint collapse, avascular head necrosis (AVN)Patient with severe articular deformity and/or instabilityFirst-stage explantations for chronic PJIOne-stage revision for chronic PJIPatient with severe arthritic condition and/or pain forced to stop working (rapid progressive osteoarthritis)Total joint arthroplasty reconstruction after bone sarcoma resectionSecond stage for treatment of an infected joint arthroplastyConversion from osteosynthesis to total joint arthroplastyOperations required because prolonged delay could prevent the appropriate surgery from being performed adequatelyPatient with severe functional impairment compromising autonomy and ability to walkPatient with inability to walk and requiring important technical aid Patient with chronic severe arthritic pain requiring opioid useEHS and EKA priority indications for elective adult hip and knee arthroplasty:Rationale Several guidelines outline the urgent indications for hip and knee arthroplasty surgery. The American College of Surgeons’ ‘COVID 19: Elective Case Triage Guidelines for Surgical Care Guidelines on Surgery’ describe the following conditions as priority indications for hip and knee arthroplasty surgery: hip dislocation, knee dislocation, periprosthetic fracture, acute pain exacerbation in prior joint arthroplasty, inability to bear weight on the extremity, wound drainage, fever and concern for periprosthetic infection.The International Consensus Group and the AAHKS Research Committee recommend priority surgery for impending fracture and exposed implants, in addition to the conditions outlined above.4.What is the role of outpatient hip and knee arthroplasty/enhanced recovery protocols in light of the SARS-CoV-2 pandemic?It would be helpful to have guidelines covering the priority indications for elective surgery for primary hip and knee arthroplasty, with a stratification of patient symptoms, disability, disease severity and soft/tissue bone compromise. Examples might include femoral head collapse in avascular necrosis, severe disability, and painful bone marrow oedema. The same should be done for revision indications, such as bone loss, impending fracture, extensor mechanism disruption, patella dislocation, severe osteolysis, massively failed implants, and second stage implantation of infections.Statement It is universally accepted that shorter hospital stays and treatment in a SARS-CoV-2-free environment decrease the risk of SARS-CoV-2 infection in patients undergoing elective surgery. Performing hip and knee arthroplasty with enhanced recovery protocols that decrease the length of stay in a facility or can be used in ambulatory care centres to allow for day surgery might be beneficial for reducing the risk of viral transmission. Transitioning to enhanced recovery systems requires full support, adoption of all the subspecialties involved and the possible approval of health care payers, which may not be possible in the pandemic setting.Rationale Enhanced recovery protocols for hip and knee arthroplasty have been shown to decrease length of stay without increasing complications in appropriate patients [patients , 44. Thepatients . TransitAlthough the quality of evidence is not very high, outpatient (day case) hip and knee arthroplasties have been shown to be safe and effective in select patients . Medicar5.What is the impact of delaying hip and knee arthroplasty for the patients themselves and for society?The American College of Surgeons’ advice is to adhere to standardised care protocols as much as possible (e.g. enhanced recovery protocols) for increased reliability in light of potential variability in available personnel, since standardized protocols optimise patient safety, minimise hospital stays and increase efficiency. They are associated with decreased complication rates.Statement Delaying elective hip and knee arthroplasty has negative consequences on the quality of life of patients and negatively impacts society as a whole. The benefits of hip and knee arthroplasty should be carefully weighed against the risks of viral transmission and infection, complications and mortality in the mostly elderly population requiring joint arthroplasty.Rationale In the face of the SARS-CoV-2 pandemic, elective hip and knee arthroplasty procedures may have been delayed or cancelled by the health authorities or by patients fearing viral spread. The consequences of delayed hip and knee arthroplasty for patients have not been studied extensively. A survey of 360 patients with cancelled arthroplasties by Brown et al. [n et al.  showed tn et al. . Becominn et al. , 34.The SARS-CoV-2 pandemic has placed an enormous economic burden on the global economy. The effect of any economic downturn is usually a decrease in elective procedures . This deWhat is the appropriate preoperative clinical and laboratory screening and timeline for patients?Statement All patients undergoing surgery should have their temperature and oxygen saturation measured [measured . A thoromeasured . HoweverRationale It is known that patients who remain asymptomatic (30% of exposed cases) or mildly symptomatic (56% of exposed cases) can transmit the infection. Taking these facts into consideration, patients who are scheduled for surgery should always be assumed to be potential carriers of the virus throughout the duration of their hospital or clinical stay, even if they pass the pre-assessment triage, including normal temperature, no history of exposure or travel and no respiratory symptoms [symptoms . Not beiNucleic acid amplification tests for viral RNA: Detection of the virus is achieved by identifying the viral RNA through nucleic acid amplification, usually using a polymerase chain reaction (PCR). The most commonly tested sample types are swabs taken from the nasopharynx (more sensitive) and/or oropharynx. Swabs are then placed into a liquid to release viral RNA into the solution and subsequently amplified using reverse transcription PCR. These tests are the gold standard for acute illness. Accuracy of the test is affected by the quality of the sample, and RNA may degrade over time. Since SARS-CoV-2 can infect anyone and result in transmission prior to the onset of symptoms, or possibly even without individuals ever developing symptoms, aggressive testing/screening of asymptomatic patients has been considered.Antibody detection via serology: The other broad category of tests include those detecting IgM, IgA, IgG or total antibodies. Clinicians should note that SARS-CoV-2 is not typically present in blood. An infection causes white blood cells to make antibody proteins that help the immune system identify the virus and stop it or mark infected cells for destruction. Development of an antibody response to infection is host-dependent and takes time. In the case of SARS-CoV-2, studies suggest that most of the patients seroconvert in 7–11 days after exposure to the virus, although some patients may develop antibodies sooner. Therefore, antibody testing is not useful in the setting of an acute illness. It is still unknown whether individuals infected with SARS-CoV-2 who subsequently recover will be protected, either fully or partially, from future infection with SARS-CoV-2 or for how long the protective immunity may last.There are two categories of SARS-CoV-2 tests: tests that detect the virus itself  and tests that detect the host’s response to the virus  :Nucleic The Dutch Medical Federation states in their guidelines that patients reporting no symptoms of SARS-CoV-2 after a thorough history taking may be either without infection, asymptomatic or pre-symptomatic. An asymptomatic patient carries the SARS-CoV2 virus but never experiences noticeable symptoms. A pre-symptomatic patient experiences no symptoms of SARS-CoV-2 at the time of evaluation but will go on to subsequently develop SARS-CoV-2 symptoms in the future. When a patient reports no symptoms of SARS-CoV-2 during preoperative screening, it is therefore impossible to make a clinically relevant distinction between the three categories of no SARS-CoV-2 infection, asymptomatic SARS-CoV-2 infection, or pre-symptomatic SARS-CoV-2 infection. This means that patients who are initially asymptomatic, pre-symptomatic or mildly symptomatic can subsequently develop moderate to severe SARS-CoV-2 disease, placing them at significant risk for adverse post-operative outcomes, that is, ICU admittance or increased mortality , 22.Concerning the chest CT, the Dutch Medical Federation’s recent advice is outlined as follows. The committee’s primary aim for the work-up for SARS-CoV-2 is to identify SARS-CoV-2-positive cases (high sensitivity) to limit transmission by rescheduling surgery, if possible, or allowing necessary precautions to be taken. Therefore, the committee initially advised that all adult patients requiring a surgical procedure under general anaesthesia undergo preoperative screening for SARS-CoV-2 infection through the use of SARS-CoV-2 PCR of a deep nasopharyngeal swab, in conjunction with a low-dose chest CT (without i.v. contrast). Preliminary data show 1–2% SARS-CoV-2 infection among preoperative patients reporting no symptoms of SARS-CoV-2. This may seem a low percentage. However operative health care workers undergo repeated exposure during aerosol-generating swab. However, the added value of chest CT is low. Therefore, the committee is of the opinion that there is no longer an indication procedures and other risk-bearing procedures. The cumulative exposure to SARS-CoV-2-positive patients for these health care workers through aerosolisation is therefore assumed to be high. In addition, transmission to other patients remains an unknown risk factor. The committee’s opinion is that this percentage justifies preoperative testing through the use of SARS-CoV-2 PCR of a deep nasopharyngeal for the use of chest CT in preoperative testing of asymptomatic patients.ESSKA guidelines focus on the SARS-CoV-2 exposure statuses of patients described by Fineberg. Risk factors  are disqualifying conditions in this early phase . The ESSKA is recommending a preoperative questionnaire; detailed discussions with the patient about their situation (e.g. by tele- or videoconference); and a SARS-CoV-2 RT-PCR test and/or immune/serology test 48 to 72 h before the operation.OrthoEvidence recommends the screening and detection of SARS-CoV-2 patients for the safe introduction of elective surgery and preservation of vital supplies.2.Is preoperative tracking of patients, staff and relatives necessary?Statement All patients and staff will need to be screened for potential symptoms of SARS-CoV-2 prior to entering a hospital facility. In particular, staff must be routinely screened for potential symptoms. Isolation prior to surgery can be guided. All patients, staff and relatives, especially those with patient contact, need to be investigated for previous symptoms, travels abroad and possible contacts with populations at high-risk for SARS-CoV-2.The International Consensus Group (ICM) and the AAHKS Research Committee recommend that testing of patients should be mandatory in high-prevalence areas, given the risk of disease transmission by asymptomatic patients. Routine testing is not feasible in all locations because of limitations in testing capacity, though, and therefore local guidelines should be followed in those areas.Rationale Park et al. [k et al.  describe3.Should spinal anaesthesia be routine?Statement Spinal anaesthesia can be considered safer for every negatively screened patient (with or without a SARS-CoV-2 test) than general anaesthesia, since the latter requires airway manipulation and endotracheal intubation, procedures that can more easily transmit SARS-CoV-2 [RS-CoV-2 .The ESSKA guidelines and the International Consensus Group (ICM) and AAHKS Research Committee recommendations have a preoperative questionnaire included which can be used for COVID-19 screening.Should only patients who also consent to regional/spinal anaesthesia be selected as candidates?Statement It cannot be made mandatory that patients consent to regional/spinal anaesthesia. Nevertheless, the benefits of regional anaesthesia should be thoroughly explained to the patients, and whenever possible, this should be strongly considered as the preferred means of anaesthesia.Rationale General anaesthesia, which requires airway manipulation, endotracheal intubation and positive ventilation, is more predisposed to transmitting SARS-CoV-2 to the anaesthetic and surgical teams. Transmission can occur from asymptomatic patients.If spinal anaesthesia does not occur, should the operation be cancelled?Statement If general anaesthesia cannot be avoided, every precaution should be taken to avoid contamination. If a SARS-CoV-2-negative environment has been achieved that is as secure as possible, then general anaesthesia with informed consent can be considered.Rationale Cancellation of surgery is a constant, agonising dilemma for nearly all health care services in terms of the wasting of resources and inconvenience caused to both patients and families. Deciding to cancel a hip or knee arthroplasty surgery means rescheduling long-anticipated, life-changing surgery for the patient. Patients undergoing elective surgery should be educated as to the spinal/general anaesthesia protocols that are in place for minimizing SARS-CoV-2 transmission to themselves, their family members, other patients and hospital personnel.OrthoEvidence clearly states that we need further research on identifying the ideal screening process for asymptomatic surgical patients, so in general anaesthesia cases, we should consider taking additional measures beyond those required for an operation under spinal anaesthesia.Surface and equipment cleaning during and between cases Wear gloves (change regularly and when soiled)Regular hand washing and avoid contamination of mucus membranes (gloved hands may remind you to not touch your mucus membranes)Avoid high-flow devices, especially if not wearing PPEConsider Video Laryngoscopy for intubation to distance yourself from the airway and/or wear mask and eye protection, sheath all reusable equipment where possible and ensure appropriate disinfection proceduresThe American Society of Anesthesiologists’ guidelines suggest that the anaesthetic professional should consider measures that limit the potential for aerosolisation of droplet particles. The following should be considered for all patients:The International Consensus Group (ICM) and the AAHKS Research Committee recommend the use of regional anaesthesia whenever possible and say it should be strongly considered for patients undergoing elective surgery during the pandemic. For patients undergoing elective surgery, education is mandatory on the protocols that are in place to minimise SARS-CoV-2 transmission to themselves, their family members, other patients and hospital personnel. An overview of the protocols implemented by the hospital to reduce the risk of transmission of the infection should be included.4.If the SARS-CoV-2 tests are positive, how long should the hip or knee arthroplasty surgery be postponed?The advice of the American College of Surgeons is to consider the guidelines in place, for personnel to be present during intubation, and to consider including a waiting period before beginning the operation to account for air circulation cycling time.Statement It is reasonable to assume that patients who test positive for SARS-CoV-2 should not be operated on and should be discharged from the hospital. These patients should remain in quarantine at least 14 days and until a subsequent test turns out negative  and they are free of fever, cough or other symptoms.Rationale Obviously, if patients show a positive result for the PCR test, they should be isolated, the national SARS-CoV-2 public health protocols should be followed (including protocols for exposed staff) and the operation should be postponed. There is no exact advice at this point with regard to the length of the postponement. Noting that hip and knee arthroplasty is elective surgery and that the patient’s safety should be optimised, then 3 weeks should be adequate, provided they do not become symptomatic.The American College of Surgeons’ advice is to have facility-specific SARS-CoV-2 testing policies which would then account for how a facility will respond to a SARS-CoV-2-positive worker, SARS-CoV-2-positive patient (identified preoperative or identified post-operative), a ‘person under investigation’ (PUI) worker or a PUI patient.Test negative from at least two consecutive NP swab specimens collected > 24 h apart orAt least 7 days have passed since symptoms first appeared.The CDC protocol is that if an asymptomatic patient tests positive for SARS-CoV-2, their operation should be rescheduled/cancelled until at least 10 days after their first positive SARS-CoV-2 test, assuming they do not subsequently develop symptoms. If they have symptoms, their operation should be rescheduled or cancelled until it has been at least 3 days since the resolution of their fever without fever-reducing medications and 3 days since any respiratory symptoms  have improved and they either:5.What kind of back-up plan is needed to guarantee quality care and patient safety in this pandemic situation?Statement The treatment of SARS-CoV-2 patients is placing a huge strain on the resources of many hospitals, to the detriment of treatment of other health problems. Safety of hip and knee arthroplasty patients remains of paramount importance. Complications of cardiac and respiratory origin are the most common problems needing acute care. As elective operations begin, every hospital should have ICU capacity available to accept and accommodate patients with cardiopulmonary or other significant complications. It should be assumed that, after the resumption of normal functions at hospitals and in society in general, there will still be a risk of another outbreak of the disease. In such a situation, hospitals should be prepared to return to a “safe mode” with reorganisation of the wards and personnel. Every hospital should have in place a plan for emergency distribution of the personnel and wards before elective surgery resumes.Rationale Co-morbidities that are common in surgical populations, including hypertension, cardiovascular disease, COPD, asthma and malignancies, also place patients at significantly higher risk of severe SARS-CoV-2 disease [ disease .The advice of the American College of Surgeons is to ensure that a post- SARS-CoV-2 outbreak, elective surgery surge will not overwhelm local facilities throughout the preoperative, intra-operative, post-operative and post-acute care phases.Is there a need for:Modification or reorganisation of hospital wards ?Statement In most orthopaedic departments, the workforces have been adjusted to accommodate fewer cases, due to the reduction in trauma cases and cancellation of elective procedures. As elective operations restart, the standard social distancing guidelines should be sufficient. Patient numbers in the clinical areas  should be halved, with the patients spaced at least 2 m apart.Rationale The International Consensus Group (ICM) and the AAHKS Research Committee recommend the following (bearing in mind that not every patient may have had a SARS-CoV-2 test):Patients should be housed in single rooms, if possible. When patients are housed in the same room, the beds should be spaced at least 2 m (6 ft) apart, and all patients should wear a surgical maskCommonly touched surfaces should be wiped down and cleaned with an effective disinfectant solution  at least twice a dayAny close contact with the patient should be done with the use of appropriate PPE, as directed by the institutional policy and in conjunction with national and local guidelinesIn the early weeks following the return to elective surgery, each patient should be placed in a single room or cubicle where check-in, registration and other administrative tasks are performed.Consideration should be given to having a screening ward to house patients, especially those who may not have been tested for SARS-CoV-2 preoperativelyLarge surgical bays with multiple patients sharing one area should be avoidedSeparation of elective and trauma orthopaedic surgery ?Statement SARS-CoV-2 screening practices should ensure the health and safety of patients and staff. SARS-CoV-2-negative elective hip and knee arthroplasty must be separated from the SARS-COV-2-positive trauma unit. Since all patients undergoing elective procedures are screened before administration, and have tested negative for SARS-COV-2, they may be reluctant to go into certain settings for fear of viral transmission. There should be a physical separation of SARS-COV-2-positive and SARS-COV-2-negative patients and specific wards should be exclusively dedicated to treating patients with SARS-CoV-2 to reduce the risk of contaminating other patients.Rationale OrthoEvidence recommends separating, when possible, known or suspected SARS-CoV-2 patients from other patients .2.Should relatives/visitors or other supportive personnel be allowed onto the orthopaedic wards and operating suite?Statement Until normality returns, the number of visitors should be minimised as much as possible to reduce potential transmission of SARS-CoV-2 among patients, their family members and medical staff. This includes sales representatives who travel to facilities to undergo, perform and support procedures. Limiting interactions between individuals and social distancing are part of the mainstream management against the spread of SARS-CoV-2. The number of visitors should be limited to those who are essential for a patient’s care. Although it is recognised that these rules create considerable anxiety for the patient, keeping all patients, relatives and staff safe from SARS-CoV-2 is the priority.Rationale All these people, including the medical device and implant manufacturer representatives, can transmit the SARS-CoV-2 virus not only from person to person at the patient’s hospital, but to other health care facilities they may visit.The use of waiting rooms should be minimised. Social distancing in the waiting rooms and other communal areas should be exercised. Frequent cleaning is also recommendedFamily members and visitors should limit the time they spend in the hospital. Some institutions may ban the entry of family members and visitors into the hospitalThe surgeon and the surgical team should avoid direct contact with family members and should update them via telephone or video conferencingThe International Consensus Group (ICM) and the AAHKS Research Committee recommend that:The preoperative setting  should consider screening all patients for symptoms of SARS-CoV-2 before their appointment, including temperature checks. All staff and others working in the facility  should be routinely screen. The American College of Surgeons is clear on this topic.3.Is there a need for extra disinfecting environmental procedures in between operations?OrthoEvidence recommends limiting or restricting patient visitors in clinical settings and screening all patients and personnel entering clinics and hospitals.Statement Standard protocols for cleaning and sterilising instruments need to be meticulously applied. Moreover, once the patient has departed from the operating room, this should be left empty for a specific period of time and all high-touch surfaces, including the anaesthetic machine and the anaesthetic work area, should be cleaned and disinfected with an Environmental Protection Agency (EPA) -approved hospital disinfectant. The length of time in between patients depends on the number of air exchanges per hour in the room or space in question. More detailed guidance is available from the US Centers for Disease Control and Prevention (CDC).Rationale The operating room and surrounding exchange areas must be sanitised as soon as possible after each procedure, with particular attention paid to all objects used in caring for patients. Similarly, all areas where SARS-COV-2 patients have transited must be carefully sanitised, too. All personnel must contribute to maintaining a clean environment, including washing floors and surfaces in general. All potentially infected single-use materials should be disposed of in IRHW containers. Reusable materials should be decontaminated, washed, dried and disinfected or sterilised, based on the likelihood of infection. Electromedical equipment  must be cleaned with a chloro-derivate solution, rinsed and dried, and then disinfected with a chloro-derivate solution in a concentration of ≥ 0.1% or 1000 ppm (parts per million) with contact time superior to 1 min, or as mandated by local guidelines. Full PPE must be worn during the sanitising procedure. Only disposable materials should be used for cleaning . Anything disposable kept inside the operating theatre during the procedure must be disposed of in IRHW containers, even if it was not used [not used .According to the American College of Surgeons, facility cleaning policies must be considered in the context of SARS-CoV-2. Cleaning  needs to be addressed along the continuum of care .4.What roles do ultra-clean operating theatres, orthopaedic exhaust suits and ultraviolet light systems play in both the wards/beds and the theatre?ECDC-Europe recommends regular cleaning followed by disinfection, using hospital disinfectants active against viruses; cleaning in patient rooms is particularly important for frequently touched surfaces. If there is a shortage of hospital disinfectants, decontamination may be performed with 0.1% sodium hypochlorite  after cleaning with a neutral detergent, although no data are available on the effectiveness of this approach against SARS-CoV-2. Surfaces that may become damaged by sodium hypochlorite can be cleaned with a neutral detergent, followed by disinfecting with a 70% ethanol solution.Statement Elective orthopaedic theatres and operative procedures, including personal protective equipment, are designed to reduce the risk of surgical site infection. There are no guidelines or protocols published for managing elective hip and knee arthroplasty procedures with respect to laminar flow in the presence of SARS-CoV-2. It is recommended that surgical helmets not be used as primary protection against aerosol and airborne disease. The surgeon should consider wearing an N95 mask as an added precaution when using a surgical helmet in patients considered to be SARS-CoV-2-negative in the preoperative work-up.Ultraviolet light has no evidence to support its routine use and poses a hazard to operating staff.RationaleHealth care providers have a duty to protect both patients and staff from cross infectionThe risk of transmission of SARS-CoV-2 between staff and patient is small when both staff and patient have been screened and tested negative. However, transmission would result in having to quarantine staff members if proper PPE has not been used.The major transmission risk is aerosol production by power tools.It is preferable that the operating room have a ventilation system with a minimum of 20 air changes per hour. Filters that are able to remove aerosol particles and droplets can be installed, while there is no actual need for negative-pressure rooms.2 concentration. N95 masks can be worn under helmets for additional protection. The International Consensus Group (ICM) and the AAHKS Research Committee advises against the use of surgical helmets in the setting of elective procedures.Previous studies performed during the SARS epidemic have shown that, commonly used commercially available surgical helmets do not filter particles of 0.02–1 μm in diameter to meet the standard for protective respirators. Unlike powered air-purifying respirators (PAPRs), which draw ambient air through a HEPA filter and blow it over the face, surgical helmets filter air through the hood material itself, placing the surgeon at risk for viral exposure. Modification of the helmet systems using additional 3D printed parts or additional filter materials being taped to the helmets have been reported but have not been tested widely. The manufacturer of one of the most popular helmets cautions against these modifications and warns against increased COESSKA guidelines state that aerosol-generating procedures (AGPs) can be defined as respiratory or surgical. Respiratory AGPs, such as intubation, are a high risk for transmitting respiratory viral infections, such as COVID-19. Surgical AGPs, such as the use of high-speed power tools, are a high risk for transmitting viruses in body fluids and body tissues; SARS-CoV-2 is known to affect all body fluids.5.What are the guidelines for personal protective equipment (PPE), in terms of availability and instructions regarding its use and what to wear in relation to the patient’s position in the perioperative chain?Although there is a debate about the necessity of laminar flow for preventing surgical site infection, there is no doubt that it is beneficial in reducing the risk of transmission of fluids between staff working in the operative field and patients. Although guidelines for surgery, which cover all surgical procedures, do not mention laminar flow and exhaust suits as primary protection against aerosol and airborne disease, their use (including a mask) for elective hip and knee arthroplasty, in which power tools are essential, should be recommended , 27, 37.Statement During hip and knee arthroplasty, the use of power tools, burrs or electrocautery generates potentially infective aerosol. The major aim should be to avoid transmission of SARS-CoV-2 by aerosolisation of blood or other body fluids. Hence, adequate personal protective equipment should be available and used during surgery. First and foremost, all patients undergoing elective surgery should wear a mask. Surgeons and the entire surgical team who scrub during procedures should ideally wear an exhaust suit, including a mask . In the absence of a face shield, protective eyewear may be used, but this is a compromise. In addition, scrubs should be frequently changed during the surgical day. Single-use gowns, single-use gloves and hair and shoe covers can also, theoretically, reduce the transmission of the virus [he virus , 29, 33.Rationale For more in-depth outcomes of the systematic review and expert opinions on this topic, see Hirschmann et al. [n et al.  on PPE uESSKA Guidelines provide extensive recommendations concerning PPE in “These should be consistent with CDC and Centers for Medicare and Medicaid (CMS) recommendations for PPEs outside the operating roomFacilities may consider having all health care workers and staff wear appropriate-level PPE, while patients wear cloth masks during the ramp-up period and possibly beyondThe American College of Surgeons mentions that PPE guidelines should include PPE recommendations for SARS-CoV-2-positive, PUI and non-SARS-CoV-2 patients for all patient care, including high-risk procedures .OrthoEvidence recommends that all surgeons working undergo PPE fit testing and review up-to-date sources for training on its appropriate use. Also, contingency plans should be developed for supply chain issues.Surgical masks are to be used in all clinical areas by staffPatients may wear either cloth masks or surgical masksFor non-clinical areas, patients and staff may wear cloth masksEye protection worn upon entry to the patient room or care areaTo address asymptomatic and pre-symptomatic transmission, implement source control for everyone entering a health care facility regardless of symptoms:N95 masks or other FDA/NiOSH approved equivalent and eye protection, gowns and gloves should be used for procedures that may lead to aerosolisation of viral particles. N95 with exhaust valves may not provide source control and also should not be used in the operating room.The current guidelines of the US CDC, along with US state, county and local regulations/guidelines, specify the following:The BMJ has an overview of the PPE advice on their website, and the revised guidelines from Public Health England recommend that health care workers caring for patients with suspected or confirmed SARS-CoV-2 should “have access to the PPE that protects them for the appropriate setting and context” and that “risk is not uniform and so elements of the updated guideline are intended for interpretation and application dependent on local assessment of risk”.Since the impact on mind and body during joint arthroplasty is significant, do the patients may have lower immunity and be more vulnerable to SARS-CoV-2 infection?Statement As SARS-CoV-2-positive is an absolute contra-indication for elective surgery, the standard enhanced recovery protocol for reducing complications is imperative.Rationale The elderly are at increased risk for adverse events. Frailty, more than age, is related to suboptimal outcomes. In addition to the standard risks, based on the currently available information and clinical expertise, adults 65 years and older, people who are overweight and people with pre-existing medical conditions  are at higher risk for severe illness and death from SARS-CoV-2.The patient’s immune function is a major determinant of the disease’s severity, and people with poor immune function, such as older people, are more vulnerable and have higher mortality with SARS-CoV-2 infection . SurgeryESSKA Guidelines emphasise that complete planning of the treatment pathway should be made available and carefully discussed with the patient prior to any operation. Care should be taken to only operate on patients when a standardised and adequate post-operative rehabilitation can be assured.The length of hospital stay for patients should be minimisedPost-operative rounds by the surgeon may be done using telemedicine, whenever possiblePatients should be discharged home and transfer to inpatient rehabilitation minimisedThe patient should be instructed on how to perform self-directed physical therapy at homePost-discharge visits to the office should be minimised, with the majority of the follow-up being done by telemedicineOffice visits should be limited to those who are having issues/complications, such as wound healing problems, suspected fracture, stiffness and so onDigital health programmes and wearable sensor technologies that allow monitoring of patients will play a larger role in management of patients in the futureSocial distancing should be resumed and at-home visits avoided, unless absolutely essentialThe International Consensus Group (ICM) and the AAHKS Research Committee recommend that the following changes be made in the post-operative care of patients during the pandemic:2.Should a shelter-in-place post-operative period, home care, community nurses or informal care be organised?OrthoEvidence recommends that patients with substantial co-morbidities and risk factors should be scheduled after healthier patients have been treated and experience has been amassed from the establishment of screening, prevention and treatment protocols.Statement Ideally, patients should be discharged home with the standard SARS-CoV-2 precautions being taken and only transferred to a nursing home in cases where that is not possible, since higher rates of SARS-CoV-2 may exist in those facilities.Rationale The communal nature of nursing homes and long-term care facilities and the characteristics of the population served  put those living in nursing homes at higher risk of infection and severe illness from SARS-CoV-2. Until normality returns, unnecessary human contact should be avoided as much as possible to reduce the potential transmission of SARS-CoV-2 among patients and their family members. All these people, including family members and nurses, can transmit the SARS-CoV-2 virus from one person to another and from one location to another.The International Consensus Group (ICM) and the AAHKS Research Committee recommend using the general principles of social distancing and minimising contact between individuals. Although no specific studies have been completed relating to the post-operative care of orthopaedic patients, logically one would expect that minimising hospital stays and minimising transfer to rehabilitation facilities or other health care settings are likely to reduce the risk for transmission of the disease.ESSKA Guidelines highlight that care should be taken to only operate on patients when a standardised protocol for adequate post-operative rehabilitation is in place.3.Consider telemedicineAvoid face-to-face contact for the orthopaedic follow-up and physical therapy guidanceThe American College of Surgeons’ advice is to evaluate and discuss the patient’s potential need for a post-acute care facility  before the operation, taking into account the known SARS-CoV-2 outbreaks in the relevant post-acute care facilities.Statement Web-based tools and telemedicine are preferred during this SARS-CoV-2 pandemic and may become the standard in the post-pandemic era.Rationale The use of internet video conferencing in health care settings (telemedicine) is widespread [despread , reflectdespread . The comdespread . This midespread . Health OrthoEvidence recommends online/telerehabilitation platforms to facilitate remote access while distancing measures are in place.Post-discharge visits to the office should be minimised, with the majority of the follow-up being done by telemedicine.Digital health programmes and wearable sensor technologies that allow monitoring of patients can play a larger role in the management of patients in the future.The International Consensus Group (ICM) and the AAHKS Research Committee recommend that the following changes be made in the post-operative care of patients during the pandemic:Minimising imaging requirementsAvoiding taking images that are unlikely to change patients’ managementPreventing unnecessary follow-up appointmentsThe AIOT Joint Statement on COVID-19 Best Practices recommends:Consider a new approach in wound closure technique in the setting of the SARS-CoV-2 pandemicPromoting telehealth modalities to increase access for diagnostic and rehabilitation purposes.Statement Post-operative in-office visits should be minimised, and digital health programmes allowing health care providers to closely monitor patients remotely should be supported. Self-administered wound management should become the standard of care for patients in the post-pandemic era.Rationale The goal of this approach is to avoid a follow-up visit at 2 weeks from the original operation. Modern, fast-track wound closure techniques need to be applied in the wake of SARS-CoV-2. Capsular closure has traditionally been performed using interrupted knotted sutures; in recent years, the number 1 knotless barbed suture has been introduced, allowing for a running technique aimed at reducing closure time, while still providing excellent results. The subcutaneous fat layer, when substantial, should be closed using synthetic, absorbable, braided sutures or bidirectional barbed sutures. Barbed sutures also demonstrate significantly less bacterial adherence than conventional braided sutures. Skin closure should be performed using 2-octyl cyanoacrylate (glue) and polyester mesh with or without monocryl running suture. This technique allows for patient self-management of the wound and offers superior cosmetic outcomes to staples. The use of video-based digital technologies will allow the health care provider to monitor the wound healing process remotely [4.What is the advice for patients who develop SARS-CoV-2 symptoms?remotely , 23, 36.Statement In the event a patient develops SARS-CoV-2 symptoms or comes into contact with a SARS-CoV-2-positive person, they should seek health care advice. The patient should use the system in place in their country to seek the relevant advice. This may be through their primary care physician or an online or telephone advice service. Their orthopaedic surgeon and hospital should also be notified.Rationale It is important to recognise the danger signs. If early symptoms of SARS-CoV-2 are missed, patients, particularly the elderly, may deteriorate rapidly before getting needed care. If the patient has a fever or acute respiratory illness, they should immediately seek health advice.OrthoEvidence recommends online or telerehabilitation platforms; this will facilitate early detection of SARS-CoV-2 symptoms by the surgeon or hospital.If you have minor symptoms, such as a slight cough or a mild fever, there is generally no need to seek medical care. Stay at home, self-isolate and monitor your symptoms. Follow national guidance on self-isolationHowever, if you live in an area with malaria or dengue fever, it is important that you do not ignore symptoms of fever. Seek medical help. When you attend the health facility, wear a mask if possible, keep at least 1-m distance from other people and do not touch surfaces with your hands. If it is a child who is sick, help the child stick to this adviceSeek immediate medical care if you have difficulty breathing or pain or pressure in the chest. If possible, call your health care provider in advance, so they can direct you to the right health care facility.The WHO advice is:The International Consensus Group (ICM) and the AAHKS Research Committee recommend that if a patient is positive for SARS-CoV-2, as determined by an RT-PCR test after a surgical procedure, all health care workers who came into contact with the patient without using PPE, and are not known to have antibodies against SARS-CoV-2, should be tested and quarantined until their test results become available. Decisions regarding the need to quarantine staff should be made in tandem with the hospital infection control team and employee health department. The patient should also be isolated and any contact with the patient should be with the use of full PPE.5.Are special adjustments needed for post-op SARS-CoV-2 prophylaxis?The American College of Surgeons mentions guidelines and considerations for post-operative SARS-CoV-2 testing of symptomatic patients or patients under investigation (PUI). Atelectasis, fevers, et cetera, are not uncommon in the post-operative course. Establishing operational guidelines for SARS-CoV-2 testing in these patients and concurrent testing results should be considered.Statement Since SARS-CoV-2-positive is an absolute contra-indication for elective surgery, the standard enhanced recovery protocol and SARS-CoV-2 preventive measures are imperative. Time allowing, all surgical patients should apply social distancing principles for the first 2 weeks after the operation and self-quarantine in their home.Rationale To date, there is no known SARS-CoV-2 prophylaxis advice; the standard enhanced recovery protocols and SARS-CoV-2 preventive actions should prevail.Wash your hands regularly with soap and water or clean them with alcohol-based hand rubMaintain at least a 1.5-m distance between you and people coughing or sneezingAvoid touching your faceCover your mouth and nose when coughing or sneezingStay home if you feel unwellRefrain from smoking and other activities that weaken the lungsPractice physical distancing by avoiding unnecessary travel and staying away from large groups of people.To prevent infection and slow transmission of SARS-CoV-2, do the following:The International Consensus Group (ICM) and the AAHKS Research Committee do not recommend that antibiotic or venous thromboembolism (VTE) prophylaxis be altered in patients undergoing elective surgery during the SARS-CoV-2 pandemic.The recommendations have been based on the available evidence and have been validated by a survey of the EHS and EKA membership . They haNational guidance for the management of the SARS-CoV-2 pandemic should be adhered to.National and local guidance for the pathway for elective arthroplasty should be followed.The recommendations can be summarised as:(i)Patient information materials should now include information on what the patient should do if they develop SARS-CoV-2 symptoms or become SARS-CoV-2 positive whilst on the elective arthroplasty pathway.(ii)Patients should only be accompanied by their primary caregiver during their elective hip or knee arthroplasty pathway.(iii)The appropriate facilities, workforce, testing and supplies for all the equipment needed must be in place.(iv)Agreed protocols should be in place for selecting suitable patients, taking into consideration the resources available to cater to their needs on an individual basis.(v)A robust testing regime for SARS-CoV-2 for both patients and staff should be in place and incorporated into the protocols for the patient journey. Being SARS-CoV-2-positive is an absolute contra-indication for primary elective hip and knee arthroplasty.(vi)Enhanced recovery protocols are encouraged, with a further reduction in the inpatient stay implemented.(vii)To reduce the risk of aerosolisation to staff, the use of spinal anaesthetic techniques is encouraged and should be included in the patient information material. An agreed policy must be in place on how to manage patients who can only undergo a general anaesthetic, which may include this being a contra-indication for surgery.(viii)Theatre staff should use personal protective equipment (PPE) in line with national and local policies. Laminar flow theatres are encouraged, and, if available, exhaust suits with a mask should be used for the operating team.(ix)Primary elective hip and knee arthroplasty patients should be physically isolated from patients admitted with trauma or for other emergencies, including the sick elderly.(x)Ideally, patients should be discharged directly back to their normal residence. Patients should be advised to maintain social distancing for 2 weeks following discharge.(xi)Post-operative rehabilitation should be implemented during the inpatient stay, with remote follow-up as the norm after discharge.(xii)Follow-up visits should be minimised and remote follow-up instituted with the relevant approvals with respect to Patient Confidentiality and Data Protection in place.In addition:


COVID-19 pandemic has markedly affected emergency care, due to sudden limitation of health care capacity by general practitioners (GP) and urgent need for infection control strategies. We evaluated the activity of the Emergency Department (ED) during the national lockdown (March 8–April 30), as well as the outcomes of our infection control strategy.p = 0.3). Diagnostic swab for COVID-19 was performed in 25% of patients, especially in subjects with co-morbidities or multiple access. Six infected cases were identified, all presenting with febrile disease. Only two positive patients fulfilled the criteria for diagnostic swab provided by the Italian Health Authorities, because of close contact with suspected or confirmed cases.Despite a reduction in access by one fifth, a proportion of febrile patients comparable to 2019 was seen . None of the 105 health-care professionals working during the study time lapse exhibited anti-SARS-CoV-2 seroconversion. Among the 589 patients with information available, 54.9% declared no medical consultation at all prior to coming to ED, while only 40 (of which 27 with fever) had been examined by their GP before coming to ED. Nevertheless, 35.6% of the cases were already taking medications. None of the 9 patients requiring intensive care reported recent pediatric consultation, despite symptoms duration up to 30 days.The rate of admission for febrile or respiratory conditions was higher than the same period of 2019 (33.4% vs 25.9%, Our results provide evidence that the reduced capacity of primary care facilities during the national lockdown may have caused a high rate of self-medication as well as a delayed provision of care in some patients. Identification of pediatric patients affected with SARS-CoV-2 infection remains a challenge because of the absence of reliable predictive factors. Finally, the use of specific triage centers, with dedicated pathways to diagnose SARS-CoV-2 infection, trace contacts and allow adequate care after swabs, is effective in preventing spreading of the infection. The pandemic of novel coronavirus  causing a cluster of respiratory infections  has rapidly transformed the healthcare system of most countries, with emergency representing one of the most affected areas. Being at the forefront of preventing and controlling the spread of SARS-CoV-2 infection, emergency clinicians had to learn quickly as much as possible about SARS-CoV-2, and to keep constantly updated about this new disease. This was made even more challenging by the fact that pediatric patients with confirmed SARS-CoV-2 infection seem to present with mild, nonspecific symptoms , with epAccording to international guidelines , our emeWe designed this multicenter retrospective study aiming to assess the effects of COVID-19 outbreak on the activity of the ED during the first national lockdown. Additional aim was to evaluate the effectiveness of our integrated infection control strategy in preventing nosocomial infections.AORN Santobono-Pausillipon (Naples) and San Giovanni di Dio e Ruggi D’Aragona University Hospital  represent tertiary emergency centers designated as Regional Spoke for screening of children with SARS-CoV-2 infection in Campania region.The two hospitals have adopted an infection control strategy Fig.  consistiIf the screening algorithm for COVID-19 suggested a suspected case, relevant diagnostic procedures  were performed into the triage tent or in a dedicated “procedure room” located at the beginning of the intra-hospital COVID path. Diagnostic procedures for red codes were performed directly into the “red codes” room, if possible.Healthcare personnel were protected by using FFP2/N95 or FFP3 face mask, eye protection goggles, isolation gown and shoes and double gloves. All patients or caretakers were provided with a surgical mask for intra- and extra-hospital transfer.After the triage, patients without suspicion of SARS-CoV-2 infection were referred to general ED rooms for further management.Subjects with suspected infection underwent a diagnostic swab. Among them, those requiring hospitalization  were transferred through a protected path into an isolation room within our COVID-unit/area until the results of the swab came back, while the rest (mild symptoms) was discharged home for isolation with monitoring by the local health services and, if a positive result of the swab returned, was called back for admission to COVID reference center. Given the wide local spreading of SARS-CoV-2 infection at the beginning of March 2020 in Campania, execution of the diagnostic swab was extended also to subjects who did not fulfill the criteria provided by the Italian Health Authorities [Patients with confirmed infection were eventually transferred from our COVID-unit to the local Infectious Diseases Services.Critically ill patients were transferred to the intensive care unit (ICU) of AORN Santobono-Pausilipon, which was identified by the regional health authorities as reference centre for suspected or confirmed COVID-19 cases needing intensive care.We retrospectively reviewed files of children and adolescents aged up to 14 years who accessed the EDs of the two hospitals from the 8th of March to the 30th of April 2020. We then extrapolated data from patients evaluated in the triage tents or presenting as red code  and clinical  data were recorded.Involvement of emergency medical transports services (i.e. ambulances), duration of symptoms, need for chest x-ray, previous medical consultation, ongoing treatments, modalities of treatment prescription, and need for intensive care were recorded, aiming to evaluate primary health care assistance of children with fever or respiratory symptoms during the pandemic.All the healthcare personnel involved in the COVID pathway  underwent an infection control surveillance consisting in systematic check before entering the hospital for body temperature and suggestive symptoms, as well as regular check for SARS-CoV-2-specific IgM and IgG every 15 to 20 days. In order to assess the efficacy of the infection control strategy, the results of all serological tests performed during the observation period were collected and analyzed.Data were retrieved from an audit performed within the two hospitals. Databases were anonymized.Confirmation of SARS-CoV-2 infection was obtained via a real-time polymerase chain reaction (RT-PCR) for SARS-CoV-2 nucleic acids on nasal + oropharyngeal swab. RT-PCR was performed at the local CDC reference laboratories .SARS-CoV-2-specific IgM and IgG were detected by Magnetic Chemiluminescence Enzyme Immunoassay using commercial kits.p value < 0.05 was considered significant for all the tests performed.Statistical analysis was performed using IBM SPSS Statistics . Data are presented as absolute numbers, percentage, means and standard deviations. Student’s T or Chi squared tests were used to compare subgroups data as appropriate. A Total access in ED among the two hospitals during the study time lapse were 2492, about one fifth of those recorded in the same period of 2019 (13342), as shown in Fig. p = 0.3). As far as it concerns severity 13 red, 109 yellow, 686 green and 21 white codes were seen, with 61 patients (7.4%) coming by emergency medical transports services. Compared to the same period of 2019, as expected the rate of white codes was significantly reduced , while interestingly the rate of red codes was significantly higher   subjects  were triaged in the tents because of symptoms suggestive of infection  had a positive diagnostic swab .Pharyngeal and nasal swab for exclusion of SARS-CoV-2 infection was performed in 207 patients (25%), of which 53 met the criteria provided by the Italian Health Authorities and, among these, 40 (75.5%) had epidemiological criteria of suspicion (40 19.3%) had epidemiological criteria of suspicion) , compared with untreated (n = 534) subjects .Information regarding primary health care assistance Table  was avaip = 0.3). The mean time between triage in tent and hospital admission was 353.5+/− 201.7 min (range 9–464). Nine patients were eventually admitted to ICU, but none of them reported recent pediatric consultation, despite mean duration of symptoms 5.9 ± 9.2 days (range 1–30 days).Compared with the same period of last year, we observed a higher percentage of hospital admission , but similar rate of admission refusals .Multiple access were recorded in 47 patients Table , of whicA total number of 105 healthcare professionals  was involved into the COVID path during the study time lapse. Each subject was tested for SARS-CoV-2 specific antibodies at least twice and none of them exhibited anti-SARS-CoV-2 seroconversion.To our knowledge, this is the first study from the South of Italy evaluating the consequences of the reduced health care capacity of pediatric primary care during the national lockdown on the activity of pediatric ED.government to establish a national lockdown from the 9th of March and until the 3rd of May, limiting the movement of the population except for necessity [Since December 2019, SARS CoV-2 infection has spread rapidly worldwide and on 11 March 2020 the World Health Organization (WHO) classified COVID-19 as a pandemic. Italy is one of the European countries most affected by COVID-19 infection, with a dizzying increase of affected cases since February 2020, inducing the Due to sudden onset of the pandemic, during the lockdown primary health care facilities and GPs had to face a lack of appropriate individual protection equipment and dedicated spaces or protocols. Thus, they started using telephone consultations or digital tools (ie WhatsApp) to triage patients, in order to assess whether it was necessary and safe to visit the patient or if the patient had to be referred to ED or other local health services for screening of SARS-CoV-2 infection or further management . As a reHowever, our data indicate that many patients continued to seek direct medical consultation in the ED, instead of getting in touch with their GP or waiting for a swab from the local health services. Indeed, despite a drastic reduction of the total access compared to the previous year, a similar proportion of subjects with febrile or respiratory conditions came to ED, in particular subjects with coexisting conditions, which are known to make the patient more vulnerable to severe forms of the infection . MoreoveUp until the 28th of April, in Italy about 20,000 healthcare workers have tested positive for SARS-CoV-2, accounting approximately for 12% of the national cases . TherefoSeveral studies from different countries , 16–18 iSimilarly, despite limitation due to the use of only serological tests for healthcare personnel, the results of our study indicate that a strategy consisting in pre-triage and triage carried out in designated areas outside the hospital, the systematic use of DPIs and dedicated pathways for patients with suspected infection is effective in limiting the intra-hospital spreading of SARS-CoV-2 infection.Interestingly, we observed a higher rate of hospital admission compared to the same period of previous year, regardless of SARS-CoV-2 positivity, suggesting that a well-structured infection control strategy might also have helped in avoiding refusal of hospitalization due to the fear of getting nosocomial SARS-CoV-2 infection. Whether this has also led to an over-exposure to diagnostic or therapeutic procedures needs to be determined in further studies. However, the large time intervals between pre-triage and eventual hospitalization indicate a significant prolongation of stay in isolation rooms identified over the COVID-pathway up to 7 h, due to the number of tests included into our emergency COVID-protocol .Finally, the results of our study confirm previous data –23 indicA detailed description of the 6 positive cases is beyond the scope of the study. However, only two of the 6 patients with confirmed infection met the criteria provided by the Italian Health Authorities , as theyOur study depicts the activity of the only two tertiary EDs in Campania region during  the first national lockdown due to SARS-CoV-2 pandemic. Our results indicate that during the national lockdown ED was considered as a safe and quick option to get a direct medical consultation. We aknowledge that a weakness of our study is mainly inherent to its retrospective design. Nevertheless, we provide clear evidence that the reduced capacity of primary care physicians may have caused a high rate of self-medication as well as a delayed provision of care in some patients. Identification of pediatric patients affected with SARS-CoV-2 infection remains a challenge because of the absence of reliable predictive factors. Finally, the use of specific triage centers, either close or far from the EDs, with dedicated pathways to diagnose SARS-CoV-2 infection, trace contacts and allow adequate care after swabs, is effective in preventing spreading of the infection and could thus guarantee high care standards.


To evaluate the penetration of carbon nanotubes (CNTs) throughout retinoblastoma in a transgenic mice model.CNTs functionalized with fluorescein isothiocyanate and targeting ligands biotin , or folic acid  were injected into the vitreous of one eye of LHP = 0.02). There was no difference in FI between eyes with CNT-FITC-Bio and CNT-FITC-FA, and FI remained stable on days 1–3 in CNT-FITC-Bio, CNT-FITC-FA, and control eyes (PNine eyes of nine mice were included in each CNT-FITC-Bio and CNT-FITC-FA groups. The mean FI in CNT-FITC-Bio was 52.08 We observed higher FI in eyes with CNT-FITC-Bio and CNT-FITC-FA compared to control eyes, showing penetration of CNTs throughout retinoblastoma. CNTs can be a carrier candidate for imaging or therapeutic purposes in retinoblastoma. Within the last decade, the use of intraarterial and intravitreal chemotherapies significantly changed the management of retinoblastoma. Prior to intraarterial chemotherapy, systemic chemotherapy provided almost 100% globe salvage in group A, B, and C eyes when coupled with laser and cryotherapy and 48% in group D eyes.,3,4 The beneficial effect of intraarterial chemotherapy was more pronounced in group D eyes by improving the globe salvage rate up to 100%.,6,7,8 However, advanced group D eyes with vitreous seeds and group E eyes continued to be a challenging problem. The use of intravitreal injection especially improved the globe salvage rate in group D eyes with extensive vitreous seeds and group E eyes increasing the globe salvage rate from 27% to 73%. The recurrence of main tumor rather than vitreous seeds was reported to be the reason of failure in globe salvage, suggesting the lack of penetration of chemotherapeutic agents in the main tumor.Retinoblastoma, a potentially deadly cancer, is the most common intraocular cancer of childhood.,12 They can be single-walled, double-walled, or multi-walled with diameters from In vivo and in vitro studies showed that CNTs have efficient drug-loading capacity with high length/diameter ratio and multifunctional surface chemistry.,1213][1[113]14]14] In addition, they are biocompatible.,13,14 All these features make CNTs an ideal candidate for consideration for drug delivery or tumor imaging. The most of current biodistribution data of CNTs has been obtained based on the systemic administration in animal models.,16 By using a three-dimensional (3D) hepatocellular carcinoma tissue culture, Wang et al showed that the surface of CNTs can be engineered to enable deep and fast penetration into tissues. This is achieved by combining the classical 3D diffusion through the interstitial gaps with accelerated two-dimensional (2D) diffusion of the CNTs over the cellular membranes. The combination of deep penetration into the tumor with the ability of CNTs to carry anticancer drugs make them promising candidates for both the diagnostics and treatment of hard-to-reach intraocular tumors.Carbon nanotubes (CNTs) are unique tubular, hollow nanostructures that have been extensively utilized in biomedical applications including implantable devices.,19 Therefore, folic acid and biotin can be ideal targets to increase CNTs uptake. In this study, we injected CNTs functionalized with ligands fluorescein isothiocyanate (FITC) and folic acid (CNT-FITC-FA) or biotin (CNT-FITC-Bio) into the vitreous of one eye with LHRetinoblastoma cells have a specialized high affinity carrier-mediated system for folic acid and biotin uptake. This animal model has been extensively characterized and develops bilateral multifocal retinal tumors that are stable and grow at the predictable rate. In this model, retinoblastoma develops when the mice is about six weeks old. When the mice reach the age of 8–10 weeks, about half of the globe is filled with the tumor, and at the age of 12–14 weeks, the entire mice globe is filed with retinoblastoma. Examination of each mice was performed and it was confirmed that retinoblastoma tumor fills about 50% of the globe.All experiments are performed in accordance with the Association for Research in Vision and Ophthalmology (ARVO) statement for the Use of Animals in Ophthalmic and Visual Research. The protocol was approved by the University Committee on Use and Care of Animals of the University of Michigan. All surgeries were performed under ketamine and xylazine anesthesia, and all efforts were made to minimize suffering. We used the LH They were also attached with FITC to image them and to evaluate their penetration. In short, 0.5 mg CNTs with an average diameter of 1.2 nm and a length of 1000 nm  were dispersed in phosphate-buffered saline (PBS) buffer followed by incubation with 8 mg of 1-ethyl-3-(3-(dimethylamino)propyl) carbodiimide (EDAC) for 1 min at room temperature, after which samples were immediately vortexed. Next, Biotin and FITC  (2 μg in 20 μL of dimethylformamide) were added together, and the resulting mixture was allowed to react for an additional 2 hours at 37°C in a rotator rocker. These samples were then washed by PBS and centrifuged at 1300 rpm for 20 min for three times to remove unbound antibodies and excess FITC in Centricon YM-50 tubes , and the resulting CNT-FITC-Bio were suspended in 1 mL of serum-free Eagle's Minimum Essential Medium (EMEM) and used immediately. Similar procedure was applied to prepare CNTs functionalized with folic acid to prepare the CNT-FITC-FA.CNTs were targeted by covalent attachment of biotin and folic acid. Receptors for biotin and folic acid are more highly overexpressed on retinoblastoma cells than retinal pigment epithelium.In this experiment, 1 µl of 0.5 mg/mL targeted CNT-FITC-Bio, and CNT-FITC-FA were injected into the vitreous of one eye of LHMice eyes were fixated with 10% formaldehyde in phosphate-buffered saline (PBS) for histology or with 4% paraformaldehyde in PBS followed by incubating with 30% sucrose in PBS. Eyes were embedded in optimal cutting temperature (OCT) compound and cryosectioned. They were stained with 4,6-diamidino-2-phenylindole  to visualize cell nuclei. we analyzed both control and injected eyes, and compared them with each other.Each globe was sectioned in to 5 µm thick sections. Five sections from each globe were evaluated and count of these five sections were averaged. The stained sections were imaged by Olympus BX-51 fluorescent microscope under 10The Difference in the fluorescein intensity between eyes injected with CNT-FITC-Bio and CNT-FITC-FA, and the control eyes were compared by using the Mann–Whitney U test. Similarly, the difference in the fluorescein intensity between eyes injected with CNT-FITC-FA and CNT-FITC-Bio were also compared by using Mann-Whitney U test. The change in the fluorescein intensity in eyes injected with CNT-FITC-FA and CNT-FITC-Bio and control eyes at different days were evaluated by using repeated measures ANOVA test.P = 0.02). We did not observe any difference in the mean fluorescein intensity between CNT-FITC-Bio and CNT-FITC-FA groups .,1617]17] Previous studies about CNTs were usually based on animal studies or 3D tissue cultures.,1617]17] In these studies, CNTs were delivered systemically to the tumor through the blood vessels and penetrated through the vessel walls or added to the 3D tissue culture medium. In this study, intravitreal CNTs penetrated and passed through the retinoblastoma tumor and reached the retinal pigment epithelium layer. This was the first study that showed that CNTs can penetrate and diffuse through a solid tumor such as retinoblastoma when injected intravitreally. Wang et al investigated the diffusional transport of CNTs in 3D tissue replica of hepatocellular carcinoma and found that diffusion coefficients of CNTs were high and comparable to the diffusion rates of similarly charged molecules with molecular weights 10000x lower. The diffusivity of CNTs in tissues was enhanced after functionalization with transforming growth factor β1. The high diffusion coefficient was attributed to the planar diffusion of CNTs along cellular membranes reducing effective dimensionality of diffusional space and electrostatic repulsion between CNT and cellular membrane. Although the penetration of CNTs remained stable on the first and second days in the eyes injected with CNT-FITC-Bio with mild increase on day 3, and the penetration increased on day 2 and remained stable on day 3 in eyes injected with CNT-FITC-FA, these changes were not found to be statistically significant. Studies with larger number of animals and longer follow-up are needed to confirm these findings and if CNTs will remain stable inside the retinoblastoma over time.Carbon nanotubes have gained tremendous attention as drug carriers or imaging tools due to their unique characteristics such as high surface area, enhanced cellular uptake, and the possibility to be easily conjugated with many therapeutic or diagnostic agents.,24,25 Abramson et al reviewed eyes treated with intravitreal chemotherapy for indications other than vitreous seeds including subretinal seeds and recurrent retinal tumors in 56 eyes of 52 patients and found the recurrence rate of retinal tumors in 19% of eyes and subretinal seeds in 11% of eyes. They concluded that intravitreal chemotherapy could be considered as adjuvant therapy in globe-sparing treatment. The penetration and diffusion of CNTs in retinoblastoma in animal models suggest that they could be an ideal carrier for chemotherapeutic agents in retinoblastoma. This might provide treatment of vitreous or subretinal seeds or retinoblastoma.With the introduction of well-tolerated intravitreal injection technique in retinoblastoma, intravitreal chemotherapy gained an attention by improving the control of vitreous seeds which were the main reason of treatment failures.There are some limitations of our study. This was a pilot study that was performed in small numbers of animals and these eyes were evaluated on days 1, 2, and 3. We did not do any electron microscopy to show the distribution of CNTs. However, higher fluorescein intensity throughout retinoblastoma tumors showed that CNTs have significantly higher penetration throughout the retinoblastoma tumors. In this study, we did not evaluate the distribution of CNTs on the other ocular structures in detail as well as their toxicities. Future studies will be needed to address these issues.In conclusion, we showed that CNTs can penetrate through the retinoblastoma tumor in a transgenic retinoblastoma model when administrated into the vitreous. There was no difference in tumor penetration between the CNT-FITC-Bio and CNT-FITC-FA groups. The deep penetration into the tumor with the ability of CNTs to carry chemotherapeutic agents make them promising carrier candidates for both diagnostics and treatment of these hard-to-reach intraocular tumors.This study was supported by Richard N and Marilyn K Witham Professorship.There are no conflicts of interest.


P = .018) and lower parallel orientation score (P = .007) were associated with malignancy. The nomogram incorporating the DL-CAD-based quantitative features, radiologists’ Breast Imaging Reporting and Data Systems (BI-RADS) final assessment (P = .014), and patient age (P < .001) exhibited good discrimination in both the development and validation cohorts . Compared with the radiologists’ BI-RADS final assessment, the DL-CAD-based nomogram lowered the false-positive rate  without affecting the sensitivity . In conclusion, the proposed model showed good performance for differentiating screening US-detected breast masses, thus demonstrating a potential to reduce unnecessary biopsies.A major limitation of screening breast ultrasound (US) is a substantial number of false-positive biopsy. This study aimed to develop a deep learning-based computer-aided diagnosis (DL-CAD)-based diagnostic model to improve the differential diagnosis of screening US-detected breast masses and reduce false-positive diagnoses. In this multicenter retrospective study, a diagnostic model was developed based on US images combined with information obtained from the DL-CAD software for patients with breast masses detected using screening US; the data were obtained from two hospitals (development set: 299 imaging studies in 2015). Quantitative morphologic features were obtained from the DL-CAD software, and the clinical findings were collected. Multivariable logistic regression analysis was performed to establish a DL-CAD-based nomogram, and the model was externally validated using data collected from 164 imaging studies conducted between 2018 and 2019 at another hospital. Among the quantitative morphologic features extracted from DL-CAD, a higher irregular shape score ( However, as mammography alone shows a low sensitivity in women with dense breasts, various supplementary imaging modalities have been investigated for screening breast cancer2. Supplemental screening breast ultrasound (US) is a widely used adjunctive tool that allows the detection of additional breast cancers in women with negative mammography2. Although the number of cancers detected varies with the prevalence of cancer, it is generally modest, with an average of 3–4 cancers per 1000 US examinations7. As most cancers detected using screening US are small, invasive and node-negative, early-stage cancer detection and management may confer a mortality benefit7.Mammography is an established modality for the early detection of breast cancer and reduction of breast cancer-related mortality and morbidity8. The Breast Imaging Reporting and Data System (BI-RADS) lexicon for breast US has contributed to the standardization of lesion characterization, description, and reporting; moreover, it has proven effective in differentiating benign and malignant breast lesions12. However, efforts to detect more cancers using screening US have led to excessive recalls and false positive biopsies. In addition, cancers detected using screening US tend to be small in size, without calcifications, and lack typical malignant features compared with palpable breast cancers or breast cancers detected using screening mammography14. Hence, the task of classifying breast masses detected using screening US as benign or malignant is challenging. Moreover, the assessment of masses detected using screening US entails concerns regarding operator dependency.Despite the well-known benefits of screening breast US, a major limitation is presented by a substantial increase in false-positive findings with low specificities and low positive predictive values15. A deep learning based computer-aided diagnosis (DL-CAD) software has been recently developed and employed for breast mass differentiation in clinical practice21. Reports on the use of the dichotomized final assessments  rendered by the current commercial DL-CAD software in patients with variable conditions showed the potential of DL-CAD with regard to improving the diagnostic accuracy and specificity21. However, to the best of our knowledge, no studies have focused explicitly on DL-CAD performance considering selected patients with breast masses detected using screening US. Considering the small size and less obvious morphologic characteristics of breast masses detected using screening US, the quantitative information derived from the DL-CAD software could provide additional details missed by the expert radiologists; furthermore, such information could prove to be substantially useful for the differentiation of breast masses while facilitating patient management in the clinical setting.Artificial intelligence, particularly involving deep learning algorithms, is gaining extensive attention owing to its excellent performance in image recognition tasksTherefore, the purpose of this study was to develop a diagnostic model that incorporates the quantitative morphologic features extracted from DL-CAD to improve the differential diagnosis of breast masses detected using screening US and reduce false-positive diagnoses.P = 0.937 and 0.444, respectively). The proportion of BI-RADS category 3 lesions was significantly higher in the development cohort than in the validation cohort . In the development cohort, there were 256 (85.6%) benign and 43 (14.4%) malignant  masses. In the validation cohort, there were 155 (94.5%) benign and 9 (5.5%) malignant  masses. The proportion of malignancy was significantly higher in the development cohort than in the validation cohort . Among the quantitative morphologic scores extracted from the DL-CAD software (Supplementary Table P < 0.001). However, the oval shape score, irregular shape score, and parallel and non-parallel orientation scores were all comparable between the two cohorts (P = 0.545–0.859).The quantitative morphologic scores were obtained using the DL-CAD software for the development and validation sets . Surgery was performed on all lesions with malignant biopsy results (n = 52) and some of the lesions with benign biopsy results (n = 81). Clinical and imaging follow-up was performed using US  for the non-excised lesions proven to be benign through biopsy (n = 330), and lesion stability was confirmed in all the cases. The characteristics of the development and validation cohorts are summarized in Table P < 0.001). All malignant breast lesions except one  had a final assessment of BI-RADS 4A or higher. In contrast, 67.6% (173 of 256) of the benign breast lesions had a final assessment of BI-RADS 4A or higher (P = 0.003). With regard to the differences in the quantitative morphologic scores obtained from the DL-CAD software between the benign and malignant breast lesions, the malignant breast lesions had a lower oval shape score , higher irregular shape score , lower parallel orientation score , higher non-parallel orientation score , lower circumscribed margin score , higher spiculated margin score , higher microlobulated margin score , lower posterior enhancement score , and higher posterior shadowing score , compared with the benign breast lesions. In the multivariable analysis, four variables were independently associated with malignancy (Table P = 0.014), older age , higher irregular shape score , and lower parallel orientation score  obtained from the DL-CAD software.The characteristics of benign n = 256) and malignant n = 43) breast lesions in the development cohort were compared using univariable logistic regression analysis, as presented in Table 56 and ma breast lP < 0.001)  and validation cohort . Moreover, the biopsy rate significantly decreased in both the development cohort  and validation cohort . The sensitivity did not significantly decrease in both the development cohort 98%  vs.  and validation cohort . When the nomogram threshold was applied to breast masses with BI-RADS 4A, 88 (50%) of the 174 masses in the development cohort and 78 (53%) of the 146 masses in the validation cohort were correctly reclassified as benign without missing any cancers  provided technical support with regard to analyzing the US images using the DL-CAD software  and obtaining outputs from the software. However, Samsung Medison Co. was not involved in the study design, data collection, statistical analysis, data interpretation, or manuscript preparation. The institutional review boards of Seoul National University Hospital (No. 1901-110-1005), Severance Hospital (4-2019-0112), and Samsung Medical Center (2019-02-051-001) approved this multicenter retrospective study, and the requirement for written informed consent was waived for re-analyzing data from prospective cohort study. All research was performed in accordance with relevant guidelines and regulations.With regard to the development cohort, the US images were collected from the prospective cohort studies performed at Severance Hospital and Samsung Medical Center, Seoul, Korea from January to December 2015. From this database, we identified patients according to the following inclusion and exclusion criteria. The inclusion criteria were asymptomatic women with breast masses detected using screening US, were scheduled for US-guided core needle biopsy, and the DL-CAD software was applied to the breast masses before performing US-guided core needle biopsy in all of the included cases. The exclusion criteria were women with breast symptoms, including lump or nipple discharge, with positive findings  obtained via mammography; the exclusion criteria also included a personal history of breast cancer, with recently diagnosed, known cancer. In total, 299 women who fulfilled the aforementioned inclusion criteria comprised the development set . To form an independent external validation cohort, we recruited patients using the same inclusion and exclusion criteria as those for the development cohort in Seoul National University Hospital, Seoul, Korea between February 2018 and June 2019. A total of 164 women  comprised the validation cohort , orientation , margin , posterior feature , echo pattern . The final assessments were provided in the dichotomized form as “possibly benign” and “possibly malignant.” The decisions regarding performing US-guided biopsy and the predetermined BI-RADS category were not altered based on the DL-CAD software results. Immediately after acquiring the DL-CAD images, the scheduled biopsy was performed.All masses included in this study were scheduled to undergo US-guided biopsy according to the predetermined BI-RADS category. The BI-RADS category was determined solely based on grayscale US images without DL-CAD information. As per the institutional rules for biopsy, all BI-RADS category 4 or 5 masses undergo biopsy, and upon the request of a clinician or patient, BI-RADS category 3 masses can be scheduled for biopsy. On the day of the scheduled biopsy, the DL-CAD software was applied using 5–12 MHz linear probes and a real-time US system  before biopsy was performed by six dedicated breast radiologists  with 6–23 years of experience. During the DL-CAD software operation, the radiologists first selected a single representative image for each mass. The representative image included the area with the most suspicious US features. The radiologists indicated the center of the mass on the selected image, and then a region of interest (ROI) was automatically drawn along the border of the mass. Manual corrections were made by the radiologists if the mass boundary was inadequately drawn by the DL-CAD software. The ROI-based US features were automatically analyzed according to the 5th edition of the BI-RADS lexiconIn this study, the quantitative morphologic scores obtained from the DL-CAD software, consisting of values between 0 and 1 for each BI-RADS lexicon descriptor, were used to develop a diagnostic model Fig.  for the 15. All the weights of each layer are not generated by human experts but learned from a large amount of data via learning procedures. In the final layer, the inputs from the previous layer are transformed to probabilities that sum to one, representing the probability distributions of the final outputs. The final decision was made by combining the output of the US lexicon features with that of the other network for classifying the ROI images30.During the generation of the quantitative morphologic scores, deep learning technology was applied to build the classifier for the BI-RADS lexicon. A deep learning network consists of a series of multiple layers of simple components, many of which compute their own non-linear mappings between the input and output. Unlike conventional machine learning techniques, which use different algorithms and trained to learn about relationship between hand-crafted image features  and clinical outcomes, deep learning obtains the complex data structures in large high-dimensional datasets to determine the manner in which the internal parameters, called weights, of a deep neural network should be adjusted to learn the representations of data with multiple levels of abstraction. The weights are used to compute the representation of data in each layer based on the output of the previous layer, and complex functions with enough components of multiple levels of representation can be learned. For classification tasks, higher layers amplify the aspects of the input that are important for discrimination and suppress irrelevant variationsAlong with the quantitative morphologic scores obtained from the DL-CAD software, the age of the patients, mass size based on the US, final BI-RADS assessment of the radiology report, and final pathological results were collected.P value < 0.1 under the univariable analysis were entered into the multivariable analysis with backward elimination. A nomogram was developed based on the multivariable logistic regression analysis. The diagnostic performance of the nomogram was evaluated in terms of discrimination and calibration. The discrimination was quantified using the area under the receiver operating characteristic (ROC) curve (AUC). The calibration was quantified using the calibration slope and intercept and visualized in the calibration curve. The internal validity of the nomogram was estimated via bootstrapping using 1000 bootstrap samples, whereas its external validity was estimated using the validation cohort. The hypothetical application of the nomogram was compared with the radiologists’ BI-RADS final assessment using the McNemar test in terms of the false positive rate, biopsy rate, and sensitivity. The cut-off of the nomogram was determined by maximizing the specificity without reducing the sensitivity to < 95% on the ROC curve. The cut-off of the radiologists’ BI-RADS final assessment was determined at category 4A. The false positive rate was defined as the number of benign breast lesions above the cut-off indicating suspicious for malignancy divided by the total number of benign lesions. The biopsy rate was defined as the number of breast lesions above the cut-off divided by the total number of breast lesions. The sensitivity was defined as the number of malignant lesions above the cut-off divided by the total number of malignant lesions. The SAS software  was used for the statistical analysis, and the R package (version 3.6.1) was used to build the nomogram.A comparison of the characteristics of the development and validation cohorts and those of the benign and malignant breast lesions in the development cohort was performed using the Chi-squared test for the categorical variables, the Wilcoxon rank sum test for the continuous variables except for age and size, and the independent t-test for age and size. Uni- and multivariable logistic regression analyses were used to identify the factors associated with malignancy in the development cohort. Variables with a Supplementary Table S1.