Inherited hemoglobin disorders, including beta-thalassemia (BT) and sickle-cell disease (SCD), are the most common monogenic diseases worldwide, with a global carrier frequency of over 5%.1 With migration, they are becoming more common worldwide, making their management and care an increasing concern for health care systems.BT is characterized by an imbalance in the α/β-globin chain ratio, ineffective erythropoiesis, chronic hemolytic anemia, and compensatory hemopoietic expansion.1 Globally, there are over 25,000 births each year with transfusion-dependent thalassemia (TDT). The currently available treatment for TDT is lifelong transfusions and iron chelation therapy or allogenic bone marrow transplantation as a curative option. SCD affects 300 million people worldwide2 and severely impacts the quality of life of patients who experience unpredictable, recurrent acute and chronic severe pain, stroke, infections, pulmonary disease, kidney disease, retinopathy, and other complications. While survival has been dramatically extended, quality of life is markedly reduced by disease- and treatment-associated morbidity.The development of safe, tissue-specific and efficient vectors, and efficient gene-editing technologies have led to the development of several gene therapy trials for BT and SCD. However, the complexity of the approach presents its hurdles. Fundamental factors at play include the requirement for myeloablation on a patient with benign disease, the age of the patient, and the consequent bone marrow microenvironment. A successful path from proof-ofconcept studies to commercialization must render gene therapy a sustainable and accessible approach for a large number of patients. Furthermore, the cost of these therapies is a considerable challenge for the health care system. While new promising therapeutic options are emerging,3,4 and many others are on the pipeline,5 gene therapy can potentially cure patients. We herein provide an overview of the most recent, likely potentially curative therapies for hemoglobinopathies and a summary of the challenges that these approaches entail.

SummaryBackground: a wrong position of bone tunnels, in particular on the femur, is one of the most frequent causes of a failed anterior cruciate ligament (ACL) reconstruction. Several studies demonstrated that drilling the femoral tunnel through the antero-medial portal (AMP) allows a more anatomical placement on the lateral femoral condyle and higher knee stability, compared to trans-tibial (TT) technique. The aim of this study was to retrospectively evaluate two groups of soccer players operated on for ACL reconstruction according to either one of these two techniques. Methods: two groups of non-professional soccer players operated on for a single bundle ACL reconstruction with hamstrings autograft using either a TT (20 patients) or an AMP (23 patients) technique were retrospectively evaluated with KT-1000 arthrometer, manual pivot shift test, isokinetic test, the incremental treadmill-running test, athletic and sport specific tasks, and knee scores (IKDC, Lysholm and KOOS). Results: the AMP group showed better results at pivot shift test and KOOS, but lower flexion angles at single leg squat test. There were no differences in all the other considered outcomes. Conclusions: the better rotational stability of the knee achieved in AMP group did not lead to sig-

nificantly better clinical and functional results in our patients. Level of evidence III. Treatment study: Case-control study.

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Background: Infections following arthroplasty are one of the major risks during this type of surgery.Case presentation: Four and half years after right hip arthroplasty surgery, the patient came back to our attention with pain at the same hip. The instrumental examinations showed signs of cup detachment and therefore, after carefully analyzing the case, we decided to perform a sterile aspiration of the hip in the operating room under C-arm fluoroscopy. Microbiological examinations showed positivity for E.Coli. The patient underwent to surgery to remove the prosthesis and implant a spacer. A therapy with Cefotaxim 2g 1-1-1 for 6 weeks was then set, after which a total arthroplasty was implanted. During this period, the Covid-19 pandemic occurred and therefore the patient performed two nasal-throat swabs, both negative. However, one week after the final surgery, respiratory conditions worsened and we performed a chest X-ray and CT scan, with suggestive images of ground-glass opacification patterns (GGO). Due to the clinic and the characteristic images of the instrumental examinations, the patient was transferred to the observation ward, waiting for the response of two additional swabs, also negative. The patient was then transferred to the ward for patients with typical symptoms of Covid-19 but with negative swabs for two weeks and subsequently discharged at home.Conclusion: Despite the concomitant Covid-19 pandemic, the guidelines in case of periprosthetic hip infection further confirm the correct management of the patient.

Background Infections following arthroplasty are one of the major risks during this type of surgery. Moreover, the outbreak of coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome CoronaVirus Disease 2), has developed into an unprecedented pandemic, posing enormous pressure on health-care providers around the world. Case presentation Four and half years after right hip arthroplasty, the patient came back to our attention with pain at the same hip. The instrumental examinations showed signs of cup detachment. After carefully analyzing the case, we decided to perform a sterile aspiration of the hip in the operating room under C-arm fluoroscopy. Microbiological examinations showed positivity for E. coli. The patient underwent surgery by which the prosthesis was removed and a spacer was implanted. A therapy with Cefotaxim 2 g three times a day for 6 weeks was then set, and then a total arthroplasty was performed. During this period, the COVID-19 pandemic occurred and therefore the patient received nasal-throat swabbing two times, and both yielded negative results. However, 1 week after the final surgery, his respiratory conditions deteriorated and chest X-ray and CT scan showed images of ground-glass opacification patterns (GGO). Due to the clinical symptoms and the characteristic images of the instrumental examinations, the patient was transferred to an observation ward. Thereafter, two more swab tests gave negative results. The patient was then transferred to the ward for patients with typical symptoms of COVID-19 but with negative swab tests for 2 weeks and was subsequently discharged home. Conclusion The purpose of this case report was to point out the correct treatment of a PJI after the outbreak of COVID-19. Despite the ongoing COVID-19 pandemic, the guidelines in the case of periprosthetic hip infection further confirmed the correct management of the patient.