Antibodies for COVID-19 - which, when and how long?

Infection with SARS-CoV2 leads to COVID-19, the severity of which derives from the host's immune response, especially the release of a storm of pro-inflammatory cytokines. This coronavirus infects by first binding to the ectoenzyme Angiotensin Converting Enzyme 2 (ACE2), a serine protease acting as the receptor, while another serine protease is necessary for priming the viral spike "S" protein required for entering the cells. Repurposing existing drugs for potential anti-coronavirus activity have failed. As a result, there were intense efforts to rapidly produce ways of providing prophylactic active immunization (vaccines) or abortive passive (convalescent plasma or monoclonal antibodies) neutralizing antibodies. The availability of vaccines for COVID-19 have been largely successful, but many questions still remain unanswered. In spite of the original enthusiasm, clinical studies using convalescent serum or monoclonal antibodies have shown limited benefit. Moreover, the emergence of Long-COVID syndrome in most infected patients necessitates the development of treatment approaches that may prevent viral entry by blocking both serine proteases involved, as with a liposomal blend of the natural flavonoids luteolin and quercetin.

Monoclonal antibody therapy in COVID-19.

Acute severe respiratory syndrome coronavirus-2 (SARS-CoV-2) infection causes coronavirus disease-2019 (COVID-19) which is associated with inflammation, thrombosis edema, hemorrhage, intra-alveolar fibrin deposition, and vascular and pulmonary damage. In COVID-19, the coronavirus activates macrophages by inducing the generation of pro-inflammatory cytokines [interleukin (IL)-1, IL-6, IL-18 and TNF] that can damage endothelial cells, activate platelets and neutrophils to produce thromboxane A2 (TxA2), and mediate thrombus generation. In severe cases, all these phenomena can lead to patient death. The binding of SARS-CoV-2 to the Toll Like Receptor (TLR) results in the release of pro-IL-1ß that is cleaved by caspase-1, followed by the production of active mature IL-1ß which is the most important cytokine in causing fever and inflammation. Its activation in COVID-19 can cause a "cytokine storm" with serious biological and clinical consequences. Blockade of IL-1 with inhibitory and anti-inflammatory cytokines represents a new therapeutic strategy also for COVID-19. Recently, very rare allergic reactions to vaccines have been reported, with phenomena of pulmonary thrombosis. These side effects have raised substantial concern in the population. Highly allergic subjects should therefore be vaccinated under strict medical supervision. COVID-19 has accelerated vaccine therapy but also the use of drugs and monoclonal antibodies (mABs) which have been used in COVID-19 therapy. They are primarily adopted to treat high-risk mild-to-moderate non-hospitalized patients, and it has been noted that the administration of two mABs gave better results. mABs, other than polyclonal plasma antibodies from infected subjects with SARS-CoV-2, are produced in the laboratory and are intended to fight SARS-CoV-2. They bind specifically to the antigenic determinant of the spike protein, inhibiting the pathogenicity of the virus. The most suitable individuals for mAB therapy are people at particular risk, such as the elderly and those with serious chronic diseases including diabetics, hypertension and obesity, including subjects suffering from cardiovascular diseases. These antibodies have a well-predetermined target, they bind mainly to the protein S (formed by the S1A, B, C and D subtypes), located on the viral surface, and to the S2 protein that acts as a fuser between the virus and the cell membrane. Since mABs are derived from a single splenic immune cell, they are identical and form a cell clone which can neutralize SARS-CoV-2 by binding to the epitope of the virus. However, this COVID-19 therapy may cause several side effects such as mild pain, bleeding, bruising of the skin, soreness, swelling, thrombotic-type episodes, arterial hypertension, changes in heart activity, slowed bone marrow activity, impaired renal function, diarrhea, fatigue, nausea, vomiting, allergic reaction, fever, and possible subsequent infection may occur at the site of injection. In conclusion, the studies promoting mAB therapy in COVID-19 are very promising but the results are not yet definitive and more investigations are needed to certify both their good neutralizing effects of SARS-CoV-2, and to eliminate, or at least mitigate, the harmful side effects.

Pain management after total knee arthroplasty: A prospective randomized study.

INTRODUCTION: Total knee arthroplasty (TKA) is a common procedure for improving mobility and quality of life in patients with osteoarthritis. Postoperative pain control management after TKA is still a concern as it relates to patients satisfaction and functional recovery.Many anesthetic regimens and techniques have been explored to decrease postoperative pain and enhance the fast recovery after TKA. The aim of this study was to evaluate the best anesthetic treatment in pain control after TKA. METHODS: 51 patients were included in a randomized prospective study and distributed in three groups. The first group (CG) in which no analgesic protocol was implemented (control group). The second group (LIA group) received an intraoperative local infiltration anesthesia (LIA) (60 ml mixture of two ropivacaine 75mg/10 mL + adrenaline 100µg/10 mL + physiological solution). The third group (FNB group) had only a femoral nerve block (FNB). Continuous outcomes including visual analogue scale (VAS) at 5,24,48 h and at 1 week, morphine consumption and range of motion (ROM) at 1,2,7 days. RESULTS: There was significant difference between all groups (p < 0,001) in terms of the VAS score: at 5h after surgery (4.55,2.15,1.82); at 24h (4.15,2.65,3.36); at 48h (3.85,2.45,2.73); at 1 week (2.95,1.80, 1.64), respectively for groups CG, LIA, FNB.ROM was better in LIA and FNB groups than CG: at 1 die after surgery (44°,50°,54°); at 3 dies (69°,70°,71°); at 7 dies (91°,98°,98°), respectively for groups CG, LIA, FNB (p < 0,001). DISCUSSION: LIA and FNB groups both showed a significant reduction at VAS score, better range of motion and less morphine consumption than CG (control group). LIA group has obtained a constant pain control in the postoperative days; FNB group had a good pain control in the hours after surgery, with a decrease in efficacy in the following days. CONCLUSION: Further studies are still needed in order to define LIA as the reference pain management in TKA.

Arthroscopy in osteochondral pathology of the elbow: indications, treatment and complications.

The arthroscopic technique has revolutionized orthopaedic surgery in the last forty years, due to the improvement in surgical technique and innovations in technologies. Actually, knee and shoulder arthroscopy are commonly used to treat the most frequent pathologies with mini-invasive approaches demonstrate recovery of function and outcomes. Not the same thing can be said for other joints such as ankle, elbow and hip, where the narrowness of the space makes the technique more challenging. In this study, a brief review of the literature and the history of elbow arthroscopy are described. Indications, surgical technique, risks and complication, tip and tricks, advices and notes to avoid complications are reported. Elbow arthroscopic surgery is a difficult technique that requires a long learning curve, but in an experienced surgeon's hands, it is a safe and successful methodology when applied with correct indications and cautions.

Comparative evaluation of meniscal pathology: MRI vs arthroscopy.

The meniscal pathology of the knee is one of the clinical realities the orthopedic surgeon must daily confront with. The diagnosis is generally both clinical and instrumental; among the different diagnostic imaging techniques, Magnetic Resonance Imaging (MRI) appears to be the most accurate method regarding sensitivity and specificity for the study of meniscal fibrocartilages and articular cartilage. In an attempt to clarify the roles of MRI and diagnostic knee arthroscopy, we performed a retrospective comparative study of the two methods to assess their sensitivity and specificity in the diagnosis of meniscal pathology. We evaluated 105 consecutive patients with a clinical diagnosis of intra-articular knee pathology who were subjected to MRI examination and subsequently to surgical arthroscopy, recording on a graphic card the surgical and radiographic findings expressed by a blinded expert radiologist. Comparison of MRI and arthroscopy data showed, for the internal meniscus, values of 98.5% sensitivity, 94.7% specificity and 93.8% "K" index for MRI compared to arthroscopy, and of 90%, 98.6% and 90.5% for the external meniscus. These results allow us to state that the diagnostic capacity of MRI appears to be very high and therefore crucial in the planning of the correct surgical treatment of individual patients, thanks to its ability to highlight even small changes affecting intra-articular structures.

Arthroscopic anatomic repair of Bankart lesion in rugby players.

Recent studies have reported equivalent outcomes of arthroscopic and open shoulder stabilization. However, surgical strategy for shoulder instability is a challenging and controversial problem for surgeons that have to treat collision sport athletes. In fact, only few studies support the arthroscopic surgery for this group of patients. The aim of this study is to evaluate the outcome of arthroscopic stabilization in a homogenous population of professional young athletes practicing in high-level collision sport. We treated 22 consecutive professional rugby players, with a mean age of 23.6 years, affected by traumatic anterior shoulder instability. All patients underwent arthroscopic Bankart repair with bone suture-anchors. Exclusion criteria were: failed previous shoulder surgery, atraumatic, multidirectional or posterior instability, bone defects greater than 20% of the anterior-inferior glenoid, engaging Hill-Sachs, rotator cuff tears, capsular-ligament avulsion on the humeral side (HAGL). Patients were evaluated according to Constant score, Rowe score and Visual Analogue Scale (VAS) for discomfort and handicap. The mean follow-up was 40.7 months (range, 6 to 87 months). All patients except one were able to return at the same previous sports level at 5 to 6 months postoperatively. Re-dislocation occurred in 3 players for high impact trauma during competition or training. Our results confirm that, also in the collision sport patients, anatomic arthroscopic Bankart repair is a good option for the treatment of traumatic anterior instability without associated lesions. .

Lesions of the biceps pulley as cause of anterosuperior impingement of the shoulder in the athlete: potentials and limits of MR arthrography compared with arthroscopy.

PURPOSE: This study aimed to evaluate the diagnostic possibilities of MR arthrography in the correct identification of complex tears of the biceps pulley and their possible correlation with anterosuperior impingement (ASI) development. MATERIALS AND METHODS: MR arthrography examinations of 23 athletes with clinical suspicion of ASI were reviewed. All examinations were obtained with a 1.5-T unit (Signa Horizon, GE Healthcare). The shoulders were studied with a dedicated surface coil with the patient's arm in the neutral position and in internal and external rotation. In five patients, images in abduction-external rotation (ABER) were obtained. Within 2 month after MR arthrography, the athletes underwent arthroscopic surgery. RESULTS: MR arthrography images showed a spectrum of tears that, according to the Habermeyer classification, were subdivided into four groups: type 1 in three patients; type 2 in five; type 3 in seven; type 4 in eight. At arthroscopic evaluation, one patient presented type 1 lesion, five type 2, five type 3 and ten type 4. During arthroscopic dynamic manoeuvres, ASI signs were observed in three patients with type 3 lesion and in ten with type 4 lesion. CONCLUSIONS: MR arthrography is the imaging modality of choice for evaluating lesions of the rotator interval structures, and only complex lesions of the biceps pulley are related to the development of ASI.

C-reactive protein changes in the uncomplicated course of arthroscopic anterior cruciate ligament reconstruction.

The diagnosis of septic arthritis following arthroscopic anterior cruciate ligament (ACL) reconstruction is often elusive and can only be confirmed by joint aspiration, although arthrocentesis carries a risk for superinfection. C-reactive protein (CRP) may prove a useful laboratory test to substantiate clinical suspicion. The present study investigated the post-operative variations of CRP in 58 patients (age range 15-52, median age 25) undergoing ACL reconstruction with either bone-patellar tendon-bone (BPTB) or hamstring tendon (HT) who did not develop infection at 6 months follow-up. CRP titre was determined on the 1st, 3rd, 7th, 15th, and 30th post-operative day by immunoprecipitation in patients divided according to the type of autograft (BPTB: 13 patients; HT: 45 patients). Mean CRP significantly increased on the 1st post-operative day, peaked on the 3rd day and decreased on the 7th day, while levels on the 15th and 30th days did not differ from baseline. The trend of CRP changes did not differ in relation to the type of autograft. The results of our study suggest that close clinical surveillance may be advisable when CRP levels deviate from the reference values 2 weeks after surgery. In these circumstances, suspicion of septic arthritis warrants aspiration and culturing in order to avert a diagnostic delay.

Health-related quality of life in patients with anterior cruciate ligament insufficiency undergoing arthroscopic reconstruction: a practice-based Italian normative group in comorbid-free patients.

BACKGROUND: Health-related quality of life (HRQoL) in anterior cruciate ligament (ACL) insufficiency has not been assessed in comorbid-free patients to date. An observational study was therefore conducted on a practice-based sample to test the hypothesis that SF-36 scoring in patients with chronic ACL insufficiency differs from the age- and gender-matched Italian norm. MATERIALS AND METHODS: Chronically ACL-insufficient patients with or without meniscal and/or focal chondral lesions were enrolled in the study. Exclusion criteria were acute ACL tear, severe and diffuse chondral lesions, concomitant knee major ligamentous injuries and/or fractures requiring surgery, previous ACL surgery and infectious, neoplastic and inflammatory disease. Knee function was evaluated by International Knee Documentation Committee (IKDC) form, HRQoL with the SF-36 questionnaire, and associated medical comorbidities by a Self-Administered Comorbidity Questionnaire (SCQ). RESULTS: A total of 316 consecutive patients, 265 males and 51 females (median age 25 years, range 15-52 years) met the inclusion/exclusion criteria. SF-36 norm-based scoring showed that the Physical Functioning, Role Physical, Bodily Pain, and Social Functioning domains were significantly lower than the Italian norm; the Role Emotional domain was also lower than the norm, but the difference was not significant. Conversely, the General Health and Mental Health domains scored significantly higher than the norm; the Vitality domain also exceeded, albeit not significantly, the norm. CONCLUSIONS: The decision-making process leading to ACL reconstruction currently emphasises the evaluation of knee function and patients' level of activity. The findings in our study, by showing that chronic ACL insufficiency significantly affects HRQoL in otherwise healthy patients, suggest that a multidimensional evaluation including HRQoL in addition to knee function might be integrated into outcome assessment.

Single-bundle versus double-bundle arthroscopic reconstruction of the anterior cruciate ligament: what does the available evidence suggest?

The introduction of the double-bundle technique as a surgical option for primary anterior cruciate ligament (ACL) surgery stems from the hypothesis that replicating the double-bundle anatomy of the native ACL improves knee kinematics by supplying better rotational control. We performed a systematic review of the literature comparing double-bundle with standard single-bundle reconstruction methods. One RCT and three quasi-RCTs with a one-to two-year follow-up were included in this review. On the basis of these studies, ACL reconstruction with a double-bundle technique leads to less residual pivot-shift as assessed on manual and instrumented tests. Conflicting results exist as to whether the double-bundle technique leads to less side-to-side anterior tibial translation, and no significant differences were found regarding proprioception, flexorextensor peak torque and knee function as assessed with the International Knee Documentation Committee score. On the other hand, better subjective knee functionwas found in one quasi-RCT. However, there is a lack of correlation between these kinematic differences and an as yet unproven clinical effect. Uncertainties also exist regarding the mid- and long-term performances of the ACL reconstructed with a double-bundle technique. Comparison between the single-bundle and double-bundle techniques should be expanded to cover unresolved issues such as the rate of complications from a more challenging surgical technique, the risk of complicating revision surgery due to the presence of two tunnels, and the cost-effectiveness of a procedure with a higher consumption of fixation devices. The doublebundle technique should be further investigated by experienced knee surgeons in studies with higher methodological quality.

Effects of anterior cruciate ligament (ACL) injury on postural control and muscle activity of head, neck and trunk muscles.

The aim of the study was to evaluate the effects that an anterior cruciate ligament injury of the knee has on postural control and activity of neck, head and trunk muscles to investigate the existence of connections between the masticatory system and body posture. Surface electromyographic activity of the muscles at mandibular rest position, and during maximal voluntary clenching and posturometric and stabilometric measurements of 25 adult patients having pathology on the left knee were compared with a control non-pathological group. At rest, the patients showed a higher muscular activity of anterior temporalis, masseter, sternocleidomastoid and lower trapezius, compared with the control subjects (P < 0.05). At maximal voluntary clenching, the patients showed a lower muscular activity of the right anterior temporalis and masseter and a higher muscular activity of the lower trapezius, compared with the control subjects. For the stabilometric measurements, all the subjects showed a significant reduction in the postural centre of pressure path length during the test with eyes open and cotton rolls, compared with the test with eyes closed and mandibular rest position (P < 0.05). In addition, the patients showed a significant displacement of the postural centre of pressure in a forward direction (P < 0.05) and into the right side (P < 0.05), compared with the control subjects. Anterior cruciate ligament injury appears to be associated to a change in the activity of head, neck and trunk muscles and to a change in the position of the postural centre of pressure. Cotton rolls seem to improve the stability of the subject.

Influence of knee pathology on body posture and muscle activity of head, neck and trunk muscles.

AIM: The aim of the study was to evaluate the effects that an anterior cruciate ligament (ACL) injury of the knee has on postural control and activity of neck, head and trunk muscles in order to investigate the existence of connections between the masticatory system and body posture. METHODS: Surface electromyographic (sEMG) activity of the muscles and their asymmetry index, at mandibular rest position, and during maximal voluntary clenching (MVC), and posturometric and stabilometric measurements of 25 patients (mean age 28+/-9 years) having undergone ACL injury of the left knee were compared with a control non-pathologic group. RESULTS: At rest, the patients showed a higher sEMG activity of the anterior temporalis, masseter, sternocleidomastoid and lower trapezius, compared with the control subjects (P<0.05). At MVC, the patients showed a lower sEMG activity of the right anterior temporalis and masseter and a higher sEMG activity of the lower trapezius, compared with the control subjects. For the stabilometric measurements, all the subjects showed a significant reduction in the Center of Pressure (CoP) path length during the test with eyes open and cotton rolls, compared with the test with eyes closed and mandibular rest position (P<0.05). In addition, the patients showed a significant displacement of the CoP in a forward direction (P<0.05) and to the righ side (P<0.05), compared with the control-subjects during each test. CONCLUSIONS: ACL injury appears to be associated to a change in the sEMG activity of head, neck and trunk muscles and to a change in the position of the CoP of the body. Cotton rolls seem to improve the stability of the subject.

[Clinical case of the month. Mental confusion due to the administration of tramadol in a patient treated with MOAI]. / Le cas clinique du mois. Confusion mentale liée à l'administration de tramadol chez une patiente sous IMAO.

However currently less used, MAOI (monoamine-oxidase inhibitor) antidepressants have specific indications like refractory or atypical depressions. The main difficulties related to MAOI therapy consist in their potentially very dangerous interactions with certain foods on the one side, many medications on the other side. For example, we report the case of a patient treated for a resistant depression by phenelzine (Nardelzine) who presented a severe delirium after the administration of tramadol (Contramal, Dolzam). This case shows the importance of particular attention before the association of any drug in a patient treated by MAOI.

Blood transfusion and deep venous thrombosis in primary total hip and knee replacement surgery: a retrospective analysis of 339 patients.

Autologous blood transfusion (ABT) has become widely practiced as a useful procedure in preventing the side effects of allogeneic blood transfusion (allo-BT) and in coping with a cost-containment policy. We report on a retrospective analysis of blood support of 339 patients undergoing orthopedic elective surgery in the period 1988-1994. We observed a progressive decrease of allo-BTs (from 54.5 to 14.8% in males and from 73.7 to 15.5% in females undergoing total hip replacement), and assessed the usefulness of post-operative blood salvage in reducing the need for allo-BT when a concomitant pre-deposit program is conducted. In addition, we carefully reviewed charts in order to establish Deep Venous Thrombosis (DVT)-related morbidity, and found a surprisingly low incidence (only 3.2%) of this dreadful complication in our patient series. It is yet to be established whether anticoagulant prophylaxis and early mobilization are strongly effective in preventing DVT, or that many DVTs happen after hospital discharge and are not identified and/or reported to the orthopedic team.

CT arthrography and arthroscopy in chronic glenohumeral joint instability.

The authors evaluate the value of CT arthrography in glenohumeral joint instability. A study was conducted on a group of 16 patients with recurrent dislocation of the shoulder. All patients underwent CT arthrography and arthroscopy. The diagnostic accuracy of CT arthrography was rated for different types of lesions on the basis of arthroscopic confirmation of its findings. Our results, which include a statistical analysis, showed a diagnostic accuracy of 97.3% in Bankart lesions and 100% in Hill-Sachs lesions and loose bodies. Dilation of the subscapular bursa and injury of the glenoid labrum-IGHL complex were often identified, while chondritis and synovitis were less frequently diagnosed. The authors therefore conclude that CT arthrography may be considered an extremely reliable diagnostic test for obtaining an overall picture of injuries due to instability. Arthroscopy, on the other hand, should be reserved for cases in which surgery may be performed in the same stage as diagnosis.

Synovial ganglia of the central pivot of the knee.

Five patients with intraarticular synovial ganglia of the knee were treated by arthroscopic surgery. These synovial cysts were found in the intercondylar fossa and appeared to originate from the cruciate ligaments. In 3 patients the ganglia were the only pathologic finding, solely responsible for the pain and functional impairment. In the other 2 patients the ganglia were accompanied by other intraarticular lesions. The diagnostic procedure (radiography, arthrography, CT, MRI, arthroscopy), confirmed the validity of CT scan and MRI in detection, differential diagnosis, and location of the ganglia in all cases. Arthroscopy enabled us to directly observe, biopsy, and remove the ganglia, resulting in immediate disappearance of symptoms and no relapse after a minimum follow-up of 20 months.

Current trends in conservative treatment of fractures of the proximal humerus.

Forty-nine fractures treated conservatively with 30 days of immobilization in a Desault bandage or a suspension cast (3 cases) are discussed. The diaphyseal index was used to check for correlation between the degree of osteoporosis and the extent and type of fracture. After an average follow-up of 6.7 months, 67% of the 36 patients reviewed had a satisfactory clinical and radiographic result and adequate healing, even those with a high degree of osteoporosis. There was no significant correlation between the type of fracture (location and degree of displacement) and the severity of bone resorption. We would emphasize that 33% of the unsatisfactory results were mostly due to the radiographic findings which, scored using the Neer system, were rated unsatisfactory even though the corresponding results were satisfactory as far as the clinical symptoms and signs. In our opinion, proximal humeral fractures in elderly patients should be treated conservatively, especially in cases of slight or moderate displacement.

Arthroscopy in the treatment of osteochondrosis dissecans of the talus.

This study consists of six cases of osteochondrosis dissecans of the talus (ODT) treated with arthroscopy, which was able to precisely evaluate the integrity of the articular surface; this exact evaluation confirmed in turn the inaccuracy of radiographic staging and often even the most sophisticated techniques (CAT scan and/or MRI). Arthroscopy allows treatment of osteochondral lesions and consensual reactive synovitis in both advanced stages and minor lesions, with recourse to transchondral perforation. Its low morbidity and short period of rehabilitation together with the subjective and objective outcome at the follow-up (4-33 months) make arthroscopy a valid alternative to arthrotomy for treating this type of lesion.

Considerations on deformity of the foot and suprasegmental pathology in infantile cerebral palsy.

The authors conducted a clinical and CT scan study of the lower limbs of patients with infantile cerebral palsy in a search for correlations between deformities of the foot and pathological conditions in other parts of the limb. This revealed that the keystone in the system is the knee, in which flexion deformity or recurvatum associated with varus or valgus and torsional deformity of the femur and tibia leads to repercussions in the foot which are reasonably predictable and constant. This contrasts with similar situations in non-neurological deformities, where repercussions in the foot are unpredictable.

Nuclear magnetic resonance as a contribution to the choice of technique in lengthening of the Achilles tendon in a spastic equinus foot.

In the search for a more accurate surgical programme for the correction of spastic equinus foot, the authors have studied the Achilles tendon with NMR before and after surgery. The results were quite interesting. Before operation, NMR provides indications as to the best technique to be adopted based on the finding of fibrotic processes involving the peritendinous tissue, in particular the Kager triangle, while, postoperatively, it allows us to evaluate the development of adherent fibrosis in relation to the different surgical techniques of lengthening adopted.