Smell loss associated with SARS-CoV-2 is not clinically different from other viruses: a multicenter cohort study.

BACKGROUND: Although the COVID-19 pandemic has increased the prevalence of cases with olfactory loss, other respiratory viruses can also cause this condition. We aimed to compare the prevalence of acute SARS-CoV-2 infection and other respiratory viruses in patients with sudden smell loss, and to assess the impact of SARS-CoV-2 viral load and co-infection on olfactory symptoms. METHODS: Patients with sudden smell loss were recruited in a multicenter prospective cohort study in 15 hospitals in Brazil. Clinical questionnaire, Connecticut Chemosensory Clinical Research Center (CCCRC) olfactory test and nasopharyngeal swab to perform a PCR-based respiratory viral panel were collected at first visit (day 0) and 30 and 60 days after recruitment. RESULTS: 188 of 213 patients presented positive test result for SARS-CoV-2, among which 65 were co-infected with other respiratory viruses (e.g., rhinovirus, enterovirus, and parainfluenza). 25 had negative test results for SARS-CoV-2. Patients in both SARSCoV-2 and non-SARS-CoV-2 groups had objective anosmia (less than 2 points according to the psychophysical olfactory CCCRC) at day 0, with no significant difference between them. Both groups had significant smell scores improvement after 30 and 60 days, with no difference between them. Co-infection with other respiratory viruses, and SARS-CoV-2 viral load did not impact olfactory scores. CONCLUSION: Patients with sudden smell loss associated with SARS-CoV-2 and other respiratory viruses had similar presentation, with most participants initiating with anosmia, and total or near total recovery after 60 days. SARS-CoV-2 viral load and co-infections with other respiratory viruses were not associated with poorer olfactory outcomes.

Sympathectomy aggravates subchondral bone changes during osteoarthritis progression in mice without affecting cartilage degeneration or synovial inflammation.

OBJECTIVE: Osteoarthritis (OA) pathogenesis involves the interaction of articular cartilage with surrounding tissues, which are innervated by tyrosine hydroxylase-positive (TH+) sympathetic nerve fibers suggesting a role of the sympathetic nervous system (SNS) during OA progression. We analyzed the effects of sympathectomy (Syx) in a murine OA model. METHODS: Peripheral Syx was generated by 6-hydroxydopamine (6-OHDA) injections in male C57BL/6 mice. OA was induced in wild-type (WT) and Syx mice by destabilization of the medial meniscus (DMM). TH+ fibers and splenic NE were analyzed to evaluate Syx efficiency. OA progression was examined by OARSI and synovitis scores and micro-CT. Expression of TH, α2A- and ß2-adrenergic receptors (AR), and activity of osteoblasts (ALP) and osteoclasts (TRAP) was investigated by stainings. RESULTS: Syx resulted in synovial TH+ fiber elimination and splenic NE decrease. Cartilage degradation and synovitis after DMM were comparably progressive in both WT and Syx mice. Calcified cartilage (CC) and subchondral bone plate (SCBP) thickness and bone volume fraction (BV/TV) increased in Syx mice due to increased ALP and decreased TRAP activities compared to WT 8 weeks after DMMWT and Syx mice developed osteophytes and meniscal ossicles without any differences between the groups. AR numbers decreased in cartilage but increased in synovium and osteophyte regions after DMM in both WT and Syx mice. CONCLUSION: Peripheral dampening of SNS activity aggravated OA-specific cartilage calcification and subchondral bone thickening but did not influence cartilage degradation and synovitis. Therefore, SNS might be an attractive target for the development of novel therapeutic strategies for pathologies of the subchondral bone.

Comparison of Gait Symmetry and Joint Moments in Unilateral and Bilateral Hip Osteoarthritis Patients and Healthy Controls.

Patients with unilateral hip osteoarthritis show a characteristic gait pattern in which they unload the affected leg and overload the unaffected leg. Information on the gait characteristics of patients with bilateral hip osteoarthritis is very limited. The main purposes of this study were to investigate whether the gait pattern of both legs of patients with bilateral hip osteoarthritis deviates from healthy controls and whether bilateral hip osteoarthritis patients show a more symmetrical joint load compared to unilateral hip osteoarthritis patients. In this prospective study, 26 patients with bilateral hip osteoarthritis, 26 patients with unilateral hip osteoarthritis and 26 healthy controls were included. The three groups were matched for gender, age and walking speed. Patients were scheduled for a unilateral total hip arthroplasty on the more affected/more painful side. All participants underwent a three-dimensional gait analysis. Gait kinematics and gait kinetics of patients and controls were compared using Statistical Parametric Mapping. Corrected for speed, the gait kinematics and kinetics of both legs of patients with bilateral hip osteoarthritis differed from healthy controls. Bilateral patients had symmetrical knee joint loading, in contrast to the asymmetrical knee joint loading in unilateral hip osteoarthritis patients. The ipsilateral leg of the bilateral patients could be included in studies in addition to unilateral hip osteoarthritis patients as no differences were found. Although patients with bilateral hip osteoarthritis show more symmetrical frontal plane knee joint moments, a pathological external knee adduction moment in the second half of stance was present in the ipsilateral leg in patients with unilateral and bilateral hip osteoarthritis. The lateral adjustment of the knee adduction moment may initiate or accelerate progression of degenerative changes in the lateral compartment of the knee.

[Growing Pains : Cause, Significance and Treatment]. / Wachstumsschmerzen : Ursprung, Bedeutung und Behandlung.

BACKGROUND: Leg pain is a common reason for consultation in the children's orthopedic clinic. It can occur across all age groups, although most patients are of pre-school or elementary school age. As there are a series of possibly severe differential diagnoses that might cause such pains in children and adolescents apart from benign pains that occur in the context of growth, a thorough patient history and physical examination are essential. PATHOGENESIS: Despite extensive research, the cause of benign growing pains has not been elucidated so far. Several possible factors play a role on an anatomical, metabolic or functional basis, ; thus, various theories exist with regard to their origin. DIAGNOSIS: Growing pains constitute a diagnosis of exclusion. If a possible organic cause of the pains is suspected, an extended diagnosis of the person affected should be made. Growing pains primarily occur at night and are always self-resolving. THERAPY: With regard to treatment, mild pain medications can be employed in more severely affected patients. It is much more important to inform family members about the benign nature of the condition. Reassuring words and physical relaxation exercises, in addition to massaging and stretching of the leg muscles, can cause a significant reduction in pain without medication.

Combined extra-/intrathoracic correction of pectus carinatum and other asymmetric chest wall deformities : A novel technique.

OBJECTIVE: Description of a novel technique to surgically correct (asymmetric) pectus carinatum and other chest deformities using a metal bar without fixation to the ribs. INDICATIONS: Severe thoracic deformity, extensive psychological strain, social isolation, pain and respiratory complaints. Pseudarthrosis or insufficient correction of a thoracic deformity after prior surgery. Distinctive deformities. CONTRAINDICATIONS: Acute infections. Postoperative intrathoracic scaring in revision cases can be challenging. SURGICAL TECHNIQUE: One-lung ventilation is used. Through two 3-4 cm long bilateral incisions to the thorax, an introducer is guided into the thorax under thoracoscopic supervision and then guided through an intercostal space out of the thorax again. A 1 cm presternal incision is performed and nylon threads are attached to the introducer bilaterally. Then the preshaped metal bar can be placed following the nylon threads. Once the metal bar is placed, the deformity is instantly corrected. Bilateral stabilizers are fixed with wire cerclage. Fixation on the ribs is not necessary. POSTOPERATIVE MANAGEMENT: Postoperative thorax x­ray. Intensive ventilation exercises. Implant removal after 2-3 years. RESULTS: The technique was used in 10 primary pectus carinatum or combined pectus carinatum and excavatum deformities as well as in 6 revision cases (3 female, 13 male, age 13-32 years). Follow-up ranged from 3-15 months postoperatively. Cosmetic results were excellent. Revision surgery required in 2 patients (one rib fracture and one local implant irritation).

Sprifermin (rhFGF18) enables proliferation of chondrocytes producing a hyaline cartilage matrix.

OBJECTIVE: Fibroblast growth factor (FGF) 18 has been shown to increase cartilage volume when injected intra-articularly in animal models of osteoarthritis (OA) and in patients with knee OA (during clinical development of the recombinant human FGF18, sprifermin). However, the exact nature of this effect is still unknown. In this study, we aimed to investigate the effects of sprifermin at the cellular level. DESIGN: A combination of different chondrocyte culture systems was used and the effects of sprifermin on proliferation, the phenotype and matrix production were evaluated. The involvement of MAPKs in sprifermin signalling was also studied. RESULTS: In monolayer, we observed that sprifermin promoted a round cell morphology and stimulated both cellular proliferation and Sox9 expression while strongly decreasing type I collagen expression. In 3D culture, sprifermin increased the number of matrix-producing chondrocytes, improved the type II:I collagen ratio and enabled human OA chondrocytes to produce a hyaline extracellular matrix (ECM). Furthermore, we found that sprifermin displayed a 'hit and run' mode of action, with intermittent exposure required for the compound to fully exert its anabolic effect. Finally, sprifermin appeared to signal through activation of ERK. CONCLUSIONS: Our results indicate that intermittent exposure to sprifermin leads to expansion of hyaline cartilage-producing chondrocytes. These in vitro findings are consistent with the increased cartilage volume observed in the knees of OA patients after intra-articular injection with sprifermin in clinical studies.

[Skeletal hemangiomas]. / Hämangiome des Knochens.

Hemangiomas are benign tumors, which are mainly composed of neoplastic blood vessels. The exact pathogenesis is still unclear. They are the most common benign spinal tumors and also occur less commonly in the bones of the extremities. Hemangiomas are often clinically asymptomatic and are diagnosed as incidental findings. Women are affected more frequently than men (2:1). The X­ray and computed tomography (CT) diagnostics typically demonstrate the classical honeycombing or vertically orientated lucencies separated by thickened cancellous bone in the affected skeletal section. Vertebral hemangiomas are hyperintense in both T1 and T2-weighted magnetic resonance imaging (MRI). The treatment of vertebral hemangiomas ranges from irradiation, embolization and vertebroplasty to operative decompression, resection of the tumor and instrumented stabilization. In the long bones intralesional curettage and bone grafting with additive osteosynthesis is the main treatment modality. The prognosis for osseous hemangiomas is good.

[EOS imaging acquisition system : 2D/3D diagnostics of the skeleton]. / EOS-Imaging : 2-D/3-D-Diagnostik des Skeletts.

The application spectrum of the EOS imaging acquisition system is versatile. It is especially useful in the diagnostics and planning of corrective surgical procedures in complex orthopedic cases. The application is indicated when assessing deformities and malpositions of the spine, pelvis and lower extremities. It can also be used in the assessment and planning of hip and knee arthroplasty. For the first time physicians have the opportunity to conduct examinations of the whole body under weight-bearing conditions in order to anticipate the effects of a planned surgical procedure on the skeletal system as a whole and therefore on the posture of the patient. Compared to conventional radiographic examination techniques, such as x-ray or computed tomography, the patient is exposed to much less radiation. Therefore, the pediatric application of this technique can be described as reasonable.

[Synovial tumors and tumor-like lesions]. / Synoviale Tumoren und tumorähnliche Erkrankungen.

Synovial tumors comprise a variety of lesions, including those with benign and aggressive neoplastic changes as well as inflammatory causes. In this article we focus on neoplastic tumors. Synovial tumors with other etiologies, such as sarcoidosis, granuloma, synovitis, or gouty arthritis, are not dealt with here. Through a precise differentiation between these disease entities can an optimization of treatment be achieved.

[Clinical evaluation of the shoulder]. / Klinische Untersuchung der Schulter.

A systematic clinical examination of the shoulder joint, including a structured medical history, is essential for the diagnosis of shoulder pathologies. Complex clinical situations that are accompanied by pain, restriction of movement, loss of strength, or instability have to be considered in accordance with the functional interaction between the cervical spine, the shoulder girdle, and the glenohumeral joint. Only accurate diagnosis allows us to apply successful therapeutic interventions. In order to achieve this, the physician needs to use standardized clinical tests and signs combined with a profound knowledge of the anatomy and the possible underlying pathologies. To ensure a structured approach as well as a complete documentation of results, a shoulder assessment form should be used. The information obtained from the history, examination, and collected data form the basis for further diagnostic imaging.

[Intra-articular punctures and injections]. / Intraartikuläre Punktionen und Injektionen.

Joint punctures and injections are a widely used approach to obtain a differential diagnostic assessment for the formation of a treatment concept for recurrent joint effusions, to exclude a periprosthetic infection in painful and loosened endoprostheses before a planned revision, to assign the origin of pain symptoms to a specific joint or to provide a treatment for arthritis of any kind. In all medical fields the standardization of processes has progressed. Therefore, for joint punctures there are standards relating to the implementation and hygiene of intra-articular punctures or injections in order to prevent the occurrence of complications, such as joint infections.

[Severe oral mucositis in a patient with HIV infection]. / Schwere orale Mukositis bei einem Patienten mit HIV-Infektion.

HISTORY AND CLINICAL FINDINGS: A 50-year-old man with HIV infection (first diagnosed > 20 years ago) presented at our hospital with fulminant oral mucositis. Antiretroviral therapy (tenofovir, emtricitabine, raltegravir) had been started 2 months ago. Previously he had no opportunistic infections and no other pre-existing illnesses. He had not travelled outside Europe but stayed in Spain for several weeks during summer. INVESTIGATIONS: Physical examination revealed swelling of the lips and severe ulcerative mucositis of the gums and pharynx. The patient complained of painful swallowing. The blood-chemistry showed no abnormalities. The microscopical analysis of a smear and a biopsy of the buccal mucosa revealed amastigotes of leishmania. By means of PCR technique, Leishmania donovani complex was specified. TREATMENT AND COURSE: The patient was treated with liposomal amphotericin B (1 mg/kg) for 21 days. Because of the immunosuppression he was put on maintenance therapy afterwards (liposomal amphotericin B every 3 weeks). However, 4 months later there was a clinical relapse of the mucositis and a new cultural and PCR detection of leishmania in a buccal biopsy. After another course of 21 days with liposomal amphotericin B (3 mg/kg) and miltefosine (150 mg/d), the mucositis subsided. Therapy with liposomal amphotericin B (3 mg/kg single dose every 3 weeks) has since been maintained. The antiretroviral therapy was changed meanwhile to lamivudin, abacavir and raltegravir because of kidney failure with elevated urea and creatinine. The patient has been clinically stable ever since without any other HIV-related problems. The latest CD4 count was 456/µl and the HIV load 340 copies/ml. CONCLUSION: Leishmaniasis is a severe infection in HIV-positive patients. Clinical manifestations can be atypical in immunosuppressed patients and the treatment is complicated with HIV coinfection. This is also due to a lifelong persistence of the parasite with potential reactivation especially in patients with suppressed CD4 cells. Therefore maintenance therapy after standard therapy of leishmaniasis is mandatory at least for a CD4 count below 350/µl. Especially in HIV patients with a leishmaniasis relapse lifelong maintenance therapy should be considered.

A review of thrombosis and antithrombotic therapy in microvascular surgery.

Despite a remarkable expansion of microsurgery, there is still no international consensus about routinely used prophylactic antithrombotic agents. Most treatment regimens still use aspirin, heparin (low-molecular-weight and unfractionated heparin) or colloids (hydroxyphenylacetate 6%/dextran); however, clear evidence for the clinical benefit of an ideal administration regimen or one agent over the other has not yet been established. Instead of searching for the one regime that fits all, an increasing number of reviews from different disciplines describe multistep approaches that optimize what has been shown to be most promising. This includes the use of antithrombotic agents, proper risk assessment, secondary prevention and professional training to optimize microsurgical skills. In this review, we describe factors included in traditional approaches and also emphasize the value of good surgical technique, which while recognized by all to be one of the most important factors for success, receives less emphasis in reviews describing thrombosis prophylaxis in microvascular surgery.

[Benign bone tumors]. / Gutartige Knochentumoren.

Benign bone tumors are neoplasms which have their origin in bone and lack criteria of malignant tumors, i.e. infiltrative growth pattern and distant metastases. They are classified according to the WHO criteria concerning the tumor matrix (osseous, cartilaginous, fibrous etc.). Traditionally there are also some non-neoplastic bone lesions which are classified as benign bone tumors and belonging to the group of tumor-like bone lesions. For the physician it is important to know those entities which are harmless, as well as those which can tend to re-occur or which ones can be locally destructive. Finally, some tumors are at risk of becoming malignant (large and proximal enchondromas or multiple tumors within a syndromal disease). Treatment is in most cases uncomplicated and can range between observation, curettage and sometimes extensive resection with complex defect reconstruction.

[Benign soft tissue tumors in orthopedics]. / Gutartige Weichteiltumoren in der Orthopädie.

For the most part soft tissue tumors are benign. However, the clinical presentation, including radiological aspects, is not always clear. Therefore, a biopsy is necessary in some cases to detect malignant tumors at an early stage. The course of even benign tumors is sometimes complicated. A not insignificant group of local, aggressive or intermediary tumors tend to recur and in exceptional cases can be fatal. Benign soft tissue tumors are subdivided according to the current WHO classification from 2002. They are classified by the tissue they mimick. In clinical practice they are additionally grouped according to aggressiveness. Some benign soft tissue tumors occur in the context of a syndrome, leading to multiple tumors. In these cases there is the threat of a tumor becoming malignant (neurofibromatosis, Maffucci syndrome).

[Osteoblasts : cellular and molecular regulatory mechanisms in fracture healing]. / Osteoblasten : Zelluläre und molekulare Regulationsmechanismen in der Frakturheilung.

Bone tissue possesses a unique regeneration ability, translating mechanical and metabolic stimuli into a biological response. The perpetual regeneration processes allow continuous self-renewal and adaptation to prevailing mechanical forces. The complex regulation of osteoblastic differentiation during fracture repair has not been completely defined. Two different transcription factors - RUNX2 and SP7 - are considered to be master genes of osteoblastic differentiation. Furthermore, the canonical WNT pathway plays an essential role in the activation of osteoblastic differentiation during both bone growth and fracture healing. Studies of fracture healing have revealed that downregulation of the WNT pathway causes a significant reduction in new bone formation. Moreover, correct WNT signalling is also required for BMP2-induced bone formation. There is increasing evidence that patients who develop recalcitrant fracture nonunions exhibit not only reduced numbers and differentiation capacity of osteogenic progenitors but also a significant downregulation of numerous factors in the WNT pathway. Therefore, better understanding of the WNT regulatory mechanisms could reveal new strategies for the treatment of delayed fracture healing and for the tissue engineering of bone.

[Tissue engineering of cartilage and bone : growth factors and signaling molecules]. / Wachstumsfaktoren und Signalmoleküle zur Anwendung im "Tissue Engineering" : Targeting und innovative Releasesysteme.

Modern tissue engineering concepts integrate cells, scaffolds, signaling molecules and growth factors. In tissue engineering of cartilage, the growth plate of the long bone represents an interesting, well-organized developmental structure, with a spatial distribution of chondrocytes in different proliferation and differentiation stages embedded in a scaffold of extracellular matrix components. The proliferation and differentiation of these chondrocytes is regulated by various hormonal and paracrine factors. This article discusses some important growth factors in the process of endochondral ossification and demonstrates how this information could be translated into a controlled release system for different tissue engineering strategies.