Dabie bandavirus (DBV), a novel Bandavirus in the family Phenuiviridae. The first case of SFTS was reported in China, followed by cases in Japan, South Korea, Taiwan and Vietnam. With clinical manifestations including fever, leukopenia, thrombocytopenia, and gastrointestinal symptoms, SFTS has a fatality rate of approximately 10%. In recent years, an increasing number of viral strains have been isolated and sequenced, and several research groups have attempted to classify the different genotypes of DBV. Additionally, accumulating evidence indicates certain correlations between the genetic makeup and biological/clinical manifestations of the virus. Here, we attempted to evaluate the genetic classification of different groups, align the genotypic nomenclature in different studies, summarize the distribution of different genotypes, and review the biological and clinical implications of DBV genetic variations.Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by  Dabie bandavirus, also known as severe fever with thrombocytopenia syndrome virus (SFTSV), Huaiyang Shan virus (HYSV), or new bunyavirus (NBV) [Bandavirus of the family Phenuiviridae. DBV infection is mainly transmitted through the bite of infected ticks, but can also be transmitted through direct contact with the bodily fluids of infected patients [Dabie bandavirus [In 2009, Hubei and Henan provinces in China reported an emerging infectious disease characterized by severe fever with thrombocytopenia syndrome (SFTS). The major clinical symptoms of the disease were fever, myalgia, gastrointestinal symptoms, dizziness, arthralgia, chills, and local lymph node enlargement. Abnormal laboratory findings included thrombocytopenia, leukopenia, and elevated serum liver enzyme levels. Researchers isolated a new bunyavirus from serum specimens of patients in the acute phase and obtained its full-length sequence. The new bunyavirus was named us (NBV) , 2. Accopatients . The incpatients . In the ndavirus –8.DBV is a negative-strand RNA virus with three genomic segments: large (L), medium (M), and small (S) . A varieReassortment, recombination, and gene variants are important factors that affect the genetic diversity and molecular evolution of DBV. Similar to other RNA viruses, DBV lacks a proofreading mechanism during viral replication and transcription and exhibits high mutation rates , 12. To In this article, the evolutionary rate and genotyping methods for DBV and some variants that may affect the biological characteristics of the virus suggested by several studies were reviewed. The relationships between three genotyping methods and differences in virulence are also discussed.Bandavirus of the family Phenuiviridae. It is a spherical, membrane-enveloped virus with a diameter of 80–100 nm. The Dabie bandavirus genome, similar to that of other members of the order Bunyavirales, is composed of three negative-strand RNA segments: large (L), medium (M), and small (S) [Phenuiviridae, the terminal sequence of the DBV genome is highly conserved. Its 3ʹ and 5ʹ ends are complementary and form a panhandle structure, and each segment resembles a closed loop [DBV is a novel virus belonging to the genus mall (S) . The gensed loop . The L fsed loop , 14. Nonsed loop , 16. Thesed loop , 18. NP sed loop , 20. Thesed loop –23.Fig. The L segment of DBV has multiple functions, such as RNA polymerase activity, endonuclease activity, and other functions related to transcription and genome RNA replication . The capNoda et al. assessed the effects of a mutation at position 1891 on the activity of the L segment using a mini-replicon assay. The results suggested that a single amino acid substitution at position 1891 of the L segment did not affect its expression level or localization. Position 1891 is located near the boundary between the arm and lasso domains. The charge of the domain edges was affected when amino acid substitutions occurred at position 1891. Basic amino acids with a positive charge increased the activity of the viral polymerase, while glutamate with a negative charge reduced polymerase activity .The three subclones E3, A4, and B7 of the YG1 strain displayed differences in fusion activity, and two amino acids were found to differ among the sequences of the envelope GPs . Tsuda eStructural analysis of DBV and other viruses belonging to genus Phlebovirus suggest that membrane fusion is triggered by structural rearrangement under acidic conditions , 36. SerTani et al. observed syncytium formation in cells expressing GPs from the YG-1 and SPL030 strains. However, in cells expressing GPs from the HB29 strain, syncytium formation was hardly induced regardless of pH. An amino acid substitution at position 962 of the GPs of HB29 (arginine → serine) (R962S) induced membrane fusion, whereas an amino acid replacement (serine → arginine) (S962R) in the GP of YG1 did not induce membrane fusion .Arginine at position 624 in domain I and histidine at position 940 in domain III may affect viral infectivity through interaction with the fusion loop region , 36. TheBrennan et al. found that an amino acid substitution at position 330 (F → S) of the M segment can lead to an increased number of larger foci in Vero cells, but the specific mechanism remains unknown . Yun et –4 (s/s/y) for the L segment, 6.76 × 10–4 s/s/y for the M segment, and 10.9 × 10–4 s/s/y for the S segment. The rate of evolution was highest for the S segment: 1.61 times greater than the M segment and 2.62 times greater than the L segment [Phlebovirus of the order Bunyavirales, finding it to be similar to that of DBV [Liu et al. calculated the evolutionary rate of each RNA segment of DBV using Bayesian analysis and found that the most recent common ancestor could be dated back approximately 182–294 years , 43. Nev segment . However segment , 46. Togt of DBV .Table 1EBunyavirales; family, Nairoviridae; genus, Orthonairovirus) showed that the existence of reassortants in the dataset could significantly affect the calculated evolutionary rate [A study of Crimean-Congo hemorrhagic fever virus  in the M segment was 0.14. The dN/dS ratio for RdRp was 0.048. Using the dN/dS ratio, the selective pressure can be described. When amino acid changes lead to a selective disadvantage, the synonymous substitution rate will be higher than the nonsynonymous substitution rate (dN/dS < 1). Although values of dN/dS were low (less than 1) for all segments of DBV, this value was significantly higher for the M segment than the other segments . This maTakahashi et al. found that isolates from Japan and China showed a close phylogenetic relationship in the evolutionary tree, but the strains were clustered into two branches, i.e., Chinese and Japanese lineages. This study used complete genome sequences, and phylogenetic trees were constructed using the neighbor-joining method .In another study, Yoshikawa et al. performed a phylogenetic analysis of 140 L segments , 171 M segments , and 211 S segments . Chinese and Japanese lineages were further divided into sublineages C1–C5 and J1-J3. Most isolates of the Chinese lineage came from China, whereas isolates of the Japanese lineage came from Japan and Korea. In addition, three Japanese isolates were clustered into the Chinese branch, and four Chinese and 26 Korean isolates were clustered into the Japanese branch. Phylogenetic trees used to analyze molecular evolution were constructed using the Maximum Likelihood Method, and complete genome sequences were used . In the The source of the strain can be displayed intuitively by naming it by region, such as the C-J genotyping method. However, as DBV gene exchange becomes more frequent and more variations arise, new genotypes may become less region-associated. As a result, genotyping based on geographical distribution may lead to misinterpretation.In the study by Fu et al., 17 strains were isolated from patients with SFTS who lived in Zhoushan, Zhejiang, and whole-genome sequencing was performed for all 17 strains. These 17 strains and another 188 strains from GenBank were included in the phylogenetic analysis. Neighbor-joining, maximum parsimony, and maximum likelihood were considered, and trees were reconstructed. The results revealed that these isolates were attributed to six genotypes (A–F). The mean genetic distance within the genotypes was 0.001–0.026 cM and the inter-genotype mean genetic distance was 0.035–0.062 cM. Genotypes A, D, and F were dominant in China, and a smaller number of isolates belonged to genotype E. Three genotypes  were present in Korea, and Japan was almost exclusively dominated by genotype B. . SubsequLiu constructed an evolutionary tree based on 122 strains using MEGA v5.02 software with the Maximum Likelihood Method. All the sequences used in this study were full-length. Phylogenetic analysis demonstrated that all segments could be divided into five lineages . DBV strains from China were distributed among the five genotypes. The Korean DBV strains belonged to genotypes A, D, and E, while the Japanese DBV strains belonged to only genotype E. A total of 55 viral strains belonged to genotype A, among which 54 strains came from China , while only one strain was isolated in South Korea. All genotype B strains were isolated in China . Genotype C contained only two strains isolated from Shandong and Jiangsu provinces. Most of the genotype D strains came from China , and only one strain came from South Korea. Strains of genotype E came from Japan, the Zhoushan Islands, and South Korea . The B aThe number of genotypes A–E was lower than that found in studies using the other two genotyping methods. Moreover, it did not report subtypes, but studies using other methods did. The two genotyping methods A–E and A–F employed many identical capital letters, but some identical letters represented different genotypes, thus making it difficult to distinguish the results based on the capital letters used.Owing to time constraints and different sources of the viral isolates, each study used different datasets. These differences resulted in different standards and nomenclatures for DBV genotyping. Further, since DBV contains three segments, researchers usually uploaded the viral segment sequences independently to databases such as GenBank, making subsequent identification of segment sequences from the same strain challenging. Moreover, the genotyping methods classified each segment independently; thus, segments from the same viral strain may be classified as different genotypes. For example, Yun et al. classified the S (MG737277), M (MG737169), and L (MG737060) segments of strain 16MS299 as subtypes B1, B2, and B1, respectively . In addiThe correspondence among results by three genotyping methods are shown in Table As shown in Table In the genotyping method that classified DBV into genotypes A–E, genotype B (A–E) corresponded to sublineage C4 (C–J) for the S and L segments, but corresponded to sublineage C5 (C–J) for the M segment. Genotype E (A–E) corresponded to sublineages J1, J2, J3, and J4 (C–J) for the S segment, but to sublineages J1, J2, and J3 (C–J) for the M segment, and to sublineages C5, C6, J1, J2, and J3 (C–J) for the L segment.When analyzing phylogenies using different sequence datasets, the phylogenetic trees will differ because of differences in the sequence datasets, including the location of certain sequences in the evolutionary tree and the number of sequences corresponding to each genotype.These genotyping methods relied on phylogenetic tree analyses without specific criteria. The results of these methods did not align well. Determining the correspondence between various genotypes is necessary when referring to multiple studies. This situation must be improved to facilitate research on the molecular biology and immunology of DBV. Establishing a unified, reliable, and practical genotyping method for DBV will largely solve this problem.Studies reporting the distribution of DBV in populations show that the most prevalent genotype in Japan and Korea is genosubtype B-2 , accounting for 86% of cases in Japan and 36.1% of cases in Korea. Genotypes D and E are also distributed in Korea, whereas genotype B is distributed only in Japan. Genotype F is the most common genotype in China, accounting for 44.1% of all cases, followed by genotype A, which accounts for 19.6% of cases. All genotypes are prevalent in China , 42. TheStrain JaOF2017-7 was discovered in southern Osaka, Japan, in 2017. Phylogenetic analysis showed that segments L and M belonged to sublineage C5, but the S segment belonged to sublineage C4  . SublineIn the studies on wildlife mentioned above, some were based on partial genomic sequence data. This may have caused a certain bias in the results, such as missing the occurrence of genome reassortment and important point mutation information; however, the partial genomic sequence contained some open reading frames with important mutation sites. In light of economic factors and medical technology levels, partial sequencing results are valuable. To provide a reference for follow-up research, we included them in the review.The genotypes of DBV are closely correlated with geographic region. The presence of a foreign genotype should be considered when identifying the strain from another endemic zone, as human cases of SFTS are characteristic of an acute disease course, and thus, the probability of interregional transmission of DBV by human carriers is low, 63. TheReassortment is an important mechanism through which RNA viruses generate new genomes. Reassortment maintains ORF integrity. Thus, the amino acid sequence remains unchanged but the entire genome segment is exchanged . ReassorWhen the L, M, and S segments of the same strain belong to different genotypes, it is assumed that the strain has undergone reassortment . Fu et aWe believe that the main reason for the reassortment of DBV is its wide host range. Therefore, natural selection pressure is also relevant . SegmentIn RNA viruses, recombination is an important mechanism for generating new genotypes . RecombiBunyavirales, can undergo homologous recombination [However, hantavirus, a member of the order bination , which hbination  discoverbination  identifibination  identifiObviously, homologous recombination may gradually increase the genetic diversity of DBV and cause changes in its antigenicity and virulence; however, the exact mechanisms and impacts of homologous recombination need to be investigated.The clinical symptoms of patients with SFTS may be related to infection with different DBV genotypes. The mortality rates of SFTS in Japan and South Korea are 35% and 23.3%, respectively . In contA recent study explored the differences in clinical manifestations and laboratory findings in patients from Henan and Zhejiang provinces. The DBV strains causing infections in Henan province mostly belonged to genotypes A, B, and D  . Most paPatients from Henan may have been infected with more than one genotype of DBV, but the existing research, data collection, and analysis are insufficient. However, the current data indicates that the clinical characteristics of patients with SFTS differ in coastal and inland areas of China. The possibility that genetic background, living environment, and treatment methods may contribute to these differences cannot be excluded. Determining whether and how genotype is related to the mechanism by which the virus causes damage and induces symptoms in the host will be interesting. Finally, more clinical data will lend power to our efforts to elucidate the relationships among viral genotypes, clinical presentations, and prognosis.In an attempt to determine the infectious activity of DBV-infected Vero E6 cells, Yun et al. reported that subtype B-1  showed the highest peak titers. The peak titers of genotypes B-2, B-3, R-1 , R-2 , R-3 , R-4 , and R-6  were found to be lower than those of subtype B-2. Genotypes A, D, F, R-5 , R-7 , R-8 , and R-9  showed the lowest titers in infected cells. Thus, in vitro infection experiments have revealed that different DBV genotypes exhibit different replication efficiency .In an DBV infection animal study, infection of aged ferrets with genotype B, including subtypes B1, B2, and B3 , and genotype D resulted in the death of all animals within 12 days of infection. High fever and significant weight loss occurred in > 20% of all animals and a high copy number of viral RNA was detected in these ferrets. Mortality was lower in aged ferrets infected with genotypes A  and F . In the reassortment genotype groups , infection with genotypes R-2 , R-3 , and R-5  caused 100% mortality and high fever. Higher peak viral RNA copy numbers were found in comparison to other reassortment genotypes. Infection with genotypes R-1 , R-4 , R-6 , and R-7  caused 80% (4/5), 60% (3/5), 40% (2/5), and 40% (2/5) of mortality in aged ferrets, respectively. Infection with genotypes R-8  and R-9  caused only 20% (5/1) mortality, low fever, and slightly elevated viral RNA copy numbers. Thus, DBV infections with genotypes B and D show higher mortality and more severe clinical manifestations, such as weight loss and fever [3 PFU, viremia occurred more often in pigeons infected with the Japanese strain JS2014 (5/8) than in those infected with the Chinese strain js2010 (2/8). When infected with 107 PFU, pigeons infected with strain JS2014-16 had a mortality rate of 12.5% at 6.8 days, with an average peak virus titer of 106.9 PFU/mL. All pigeons infected with the JS2010-14 strain survived for more than 6.1 days with an average peak titer of 105.6 PFU/mL, which was significantly lower than that of pigeons infected with strain JS2014-16. Moreover, infection with strain JS2014 caused earlier and more severe weight loss [Li et al. used two major viral genotypes to infect spotted doves: strain JS2014-16  and strain JS2010-14 (genotype F), which are prevalent in East Asia. When infected with 10These results indicated that strain JS2014-16 may be more virulent than strain JS2010-14. It can be inferred from these results that genotype B induces high mortality and has high pathogenicity, which is consistent with the statistics of DBV infection in the human population. This study provided clear evidence supporting differences in virulence among different genotypes.DBV has been identified in several countries. In China, the genetic and genotypic diversity of DBV are relatively high. Reassortment and recombination are important driving forces for the evolution of DBV. Reassortment may lead to novel combinations of genome segments derived from different parental strains, and this phenomenon has been found to be common in DBV. Several attempts have been made to genotype DBV. However, the current DBV genotyping system is confusing because of the lack of uniform standards among different genotyping methods. The establishment of a standard genotyping method based on a large and representative sequence database is urgently required for the following reason: Firstly, the RdRp of RNA viruses lacks a proofreading function; as a result, mutations can be easily generated in the genome of RNA viruses. Genetic mutations in DBV have been associated with changes in certain biological functions, such as viral infection and replication. Studies on mutations at the amino acid level will improve our understanding of the functions of individual viral proteins and their mechanisms and roles in viral pathogenesis. Secondly, animal studies have shown that different DBV strains have different symptoms and fatality rates. These observations strongly indicate that different genotypes of DBV might differ in their pathogenicity, but very few studies have examined this issue to date. Accurate genotyping can help elucidate the relationship between different virus strains and their clinical manifestations. Furthermore, previous studies have indicated that the long-distance spread of DBV is associated with migratory bird movements. Researchers can track changes in viral genotypes in the local environment. Thus, genotyping can provide guidance for the identification of new or imported cases. In summary, reliable genotyping will help to lay a solid foundation for the systematic investigation of the epidemiology, biology, and pathogenesis of DBV.


Approximately 30 % of population can have an accessory spleen, which is most often asymptomatic. Only when it becomes large in size, it may elicit symptoms, mostly due to complications, such as torsion, infarction, or traumatic hemorrhage. The preoperative diagnosis of an accessory spleen is often challenging due to its propensity to manifest the neoplasms of adjacent organs. Here we report a rare case of a huge tortured accessory spleen mimicking splenic lymphangioma and to review the literature.A 27-year-old man was admitted to the emergency department following left hypochondrial pain that lasted for three days. The computed tomography scan findings demonstrate the spleen in its normal position, showing smooth outlines attached to a similar-density cystic heterogenous mass exhibiting strong radiological evidence of splenic lymphangioma. Surgical excision was performed, and a large tortured accessory spleen was discovered that was attached to the lower pole of the spleen by connective tissue.An accessory spleen is always smaller than 4 cm, and accessory spleens larger than that, especially with torsion, are extremely uncommon. According to literature, the identification of accessory spleen on the basis of clinical and radiological features is very difficult, especially when the patient presents with symptoms of acute abdomen.Considering the fact that accessory splenic tissue can mimics neoplasms of the spleen or nearby organs, it should be included in the differential diagnosis in an undiagnosed pre- or intraoperative hypochondrial mass, located in the vicinity of the spleen. •Accessory spleen can be found in 10 to 30 % of the papulation and has an asymptomatic nature.•Preoperative diagnosis of the accessory spleen is very difficult because it usually mimics neoplasms of nearby affected organs.•An accessory spleen is always smaller than 4 cm, and accessory spleens larger than that, especially with torsion, are extremely uncommon.•Most of the accessory spleen are diagnosed by pathological examination and during surgery. It is t2A 27-year-old man was admitted to the emergency department due to persistent left hypochondrial pain of three days duration. The patient was haemodynamically stable, with a blood pressure of 100/60 mmHg and a pulse rate of 88/min. Laboratory exams, including peripheral blood counts and tumor markers (CEA and CA125), were normal. The post-contrast CT scan from the abdomen demonstrates the spleen in its normal position, showing homogeneous density with smooth outlines accompanied by another cystic heterogenous lesion with similar density as that of the spleen in the left upper quadrant, that was attached to the lower pole of the spleen, compressing the left kidney, with no infiltration or invasion of surrounding structures, exhibiting radiological evidence strongly suggestive of splenic lymphangioma A. An exp3Streptococcus pneumoniae, Hemophilus influenza and Neisseria meningitidis [The spleen is one of the most important organs of immune system . In factngitidis . Congeningitidis . By defingitidis . On the ngitidis ,13. Suchngitidis ,14,15. Mngitidis ,17. An angitidis . Sometimngitidis .Nuclear scanning utilizing colloid labeled with Technetium 99 can makes the spleen's parenchyma visible and recognizable and therefore, it is the only radiological modality of choice for confirmation of the diagnosis but also for accurately locating the ASs . UnfortuBased on reviewed articles in the literature we found seven cases of ASs larger than 8 cm and only one reported case larger than our case which is listed in 4Our extensive literature review demonstrated that the diagnosis of AS is difficult, especially when the presentation is as an acute abdomen or as is in our case. The misdiagnosis is mostly including neoplastic disease, lymphadenopathies, and cysts, which leading to unnecessary excision of the ASs. Therefore, an undiagnosed pre- or intraoperative mass, which is located closely to the spleen have to be managed carefully. Intra-operative evaluation and histopathological examination remain as the modalities of choice for accurate diagnosis of AS.Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.Since this was a retrospective observational study and did not involve actual patient, patient's images or videos, it was granted an exemption from requiring ethics approval from the institutional Ethics Review Committee (ERC).No financial support was provided for this study.Jamshid Abdul-Ghafar, MD, PhD, FRCPathN/A.JAG and MH diagnosed the case. MH conceived the idea. MH contributed to the writing of the manuscript's first draft. JAG, AMH and HAM were major contributor to the critically revising of the manuscript and important intellectual content. FRF was a major contributor of radiological image description. All authors read and approved the final manuscript.The authors declare that they have no competing interests.


The aim of this study was to assess the biomechanical effects of subtalar ligament injury and reconstruction on stability of the subtalar joint in all three spatial planes.Fifteen fresh frozen cadaveric legs were used, with transfixed tibiotalar joints to isolate motion to the subtalar joint. An arthrometer fixed to the lateral aspect of the calcaneus measured angular displacement in all three spatial planes on the inversion and eversion stress tests. Stress manoeuvres were tested with the intact joint, and then repeated after sequentially sectioning the inferior extensor retinaculum (IER), cervical ligament (CL), interosseous talocalcaneal ligament (ITCL), arthroscopic graft reconstruction of the ITCL, and sectioning of the calcaneo-fibular ligament (CFL).Sectioning the ITCL significantly increased angular displacement upon inversion and eversion in the coronal and sagittal planes. Reconstruction of the ITCL significantly improved angular stability against eversion in the axial and sagittal planes, and against inversion in the axial and coronal planes, at the zero time point after reconstruction. After sectioning the CFL, resistance to eversion decreased significantly in all three planes.Progressive injury of ligamentous stabilisers, particularly the ITCL, led to increasing angular displacement of the subtalar joint measured with the inversion and eversion stress tests, used in clinical practice. Reconstruction of the ITCL using tendon graft significantly stabilised the subtalar joint in the axial and sagittal planes against eversion and in the axial and coronal planes against inversion, immediately after surgery. The subtalar joint enables translation in all three planes between the foot and the rest of the lower limb, and is key for adequate hindfoot mechanics during the loading response of the hindfoot between the initial heel contact and the mid-stance phases of the gait cycle. Its stability resides in the configuration of the anterior and posterior subtalar joint surfaces as well as several ligamentous structures Fig.  6, 25, , 25, 27:Subtalar joint instability is an entity commonly neglected within the scope of lateral ankle instability in patients of all ages; up to 25% of chronic ankle instabilities have associated subtalar instability , 30, whiControversy exists surrounding the main structures injured that contribute to subtalar instability; some authors consider the ITCL and CL the main stabilisers of the joint, while others defend the CFL ligament’s role –32, 34. The subtalar joint is hypothesised by the authors of this study to be stabilised by allograft reconstruction of the ITCL, under cadaver-simulated conditions of subtalar instability. Determining the contribution of the IER, CL, ITCL and CFL on subtalar joint stability in all three spatial planes, as well as the effect of ITCL allograft reconstruction on angular stability of the subtalar joint in a cadaveric model, was a secondary goal.Fifteen fresh frozen cadaveric ankles without deformities, morphologic alterations or scars were used. The study was performed at the Department of Anatomy of the Francisco de Vitoria University in Madrid, Spain, and fulfilled local legal and ethical criteria for cadaveric studies (study number 001/2018). The corpses proceed from the University’s Body Donation Program that had been stored at – 15 °C and slowly thawed for at least 24 h prior to the study to avoid stiffness that would interfere with measurements. Each specimen was sectioned below the knee joint maintaining at least 20 cm of tibia and fibula.An arthrometer specifically designed to measure angular displacements in all three anatomic planes   was usedx > 0), while negative values (x < 0) corresponded to internal rotation. In the coronal plane, inversion received positive values, while eversion was measured in negative values. In the sagittal plane, positive values corresponded to plantarflexion and negative values to dorsiflexion.In the axial plane, external rotation was assigned positive values (The stability manoeuvres performed were the inversion stress test (IST) and eversion stress test (EST) . In the 1. Initially, with the subtalar joint intact, the following manoeuvres were performed: inversion (I) and eversion (E), plantar flexion (PF) and dorsiflexion (DF), internal rotation (IR) and external rotation (ER), and the angular displacement detected by the arthrometer in the three anatomical planes was recorded.2. Next, the IER was sectioned and the stability examination manoeuvres were repeated.3. Next, the CL was sectioned and the stability examination manoeuvres were repeated.4. The ITCL was then sectioned and the stability examination manoeuvres were performed.® system  at the talar end and a 6.25 mm biotenodesis screw  at the calcaneal end, with the subtalar joint in slight eversion and dorsiflexion  and the margin of error of the measurement device , 41, witp < 0.05. Data was analysed using SPSS 21.0® for Windows .Qualitative variables are presented as frequencies and percentage values, while quantitative variables are summarised as median and interquartile ranges because the sample was too small Table . StatistFor the IST, sectioning the ITCL added to laxity in the coronal and sagittal planes, and ligament reconstruction returned stability to practically normal values. When evaluating varus displacement in the coronal plane, sectioning the ITCL led to increasing instability. Sectioning the CFL after ITCL reconstruction did not appear to have any significant effect. Ligament reconstruction returned stability in the coronal plane, while sectioning the CFL significantly affected stability against varus. In the sagittal plane, sectioning the retinaculum affected stability against plantarflexion more than sectioning the cervical ligament; injury to the ITCL had a significant effect on joint laxity that was remedied by ligament reconstruction.For the EST, when assessing rotation in the axial plane, sectioning the CL significantly increased external rotation, but adding injury of the ITCL did not add to rotational instability. Laxity restoration against external rotation improved significantly when reconstructing the ligament and deteriorated when adding injury to the CFL. Upon examination of valgus displacement in the coronal plane, neither injuring the retinaculum nor the CL had an effect on valgus laxity of the subtalar joint, but sectioning the ITCL did show a significant effect. Ligament reconstruction showed values similar to the sectioned IER, but adding CFL injury added to valgus laxity in the coronal plane. In the sagittal plane, injuring structures sequentially led to increasing instability in dorsiflexion. Ligament reconstruction returned laxity to nearly normal values. Sectioning the CFL affected laxity in dorsiflexion.Reconstruction of the ITCL significantly improved angular stability of the subtalar joint against eversion in the axial, and sagittal planes, and against inversion in the axial and coronal planes, at the zero time point after reconstruction.In the comparative study of the intact subtalar joint and the reconstruction, no statistically significant differences were found, except in the axial plane with the inversion manoeuvre (p = 0.001), which can be interpreted as the reconstruction stabilising the subtalar joint in the inversion manoeuvres in the coronal (n.s.) and sagittal (n.s.) plane and in the eversion manoeuvre in the axial (n.s.), coronal (n.s.) and sagittal (n.s.) planes Fig. .Fig. 4AnThe most important finding of this study was the biomechanical contribution of the different ligaments around the subtalar joint on angular displacement in all three anatomical planes and the effect of graft reconstruction of the interosseous talocalcaneal ligament. Injury to the ITCL added to laxity in the coronal and sagittal planes upon inversion, and ligament reconstruction returned stability to practically normal values. Sectioning the CFL after ITCL reconstruction did not appear to have any significant effect against inversion, but increased laxity in external rotation upon eversion.Recent studies were unable to identify a specific ligament that acted as the main stabiliser of the subtalar joint, and suggested that the ligaments act in conjunction against a combination of movements, stabilising the joint in all three planes , 28. EveThe IER was observed to restrict subtalar movement in the axial plane  in inversion and to a lesser degree in eversion. The CL ligament stabilised against external rotation in eversion, in agreement with Kjærsgaard-Andersen et al. , but notRelatively few studies describe surgical techniques for treatment of subtalar instability. Though the trend is towards anatomic reconstruction of the damaged structures and use of arthroscopically assisted techniques, most studies are limited to retrospective case series with a limited number of patients and variable follow-up, without any biomechanical rationale supporting the proposed techniques , 14, 21.Several strengths can be found in this study: no evaluations of angular stability through biomechanical studies after reconstructing the ITCL are known to us. It is a cadaveric study with a relatively large sample size and a rigorous protocol to minimise measurement errors using a validated measurement device already used in other biomechanical studies of the ankle .We are aware of the limitations of our study. First, our analysis has the limitations inherent to cadaver studies. Allograft reconstruction was studied without considering the fibrosis of the subtalar joint that would be present in a live patient with injured ligaments and that would also contribute to joint stability. The effect of the posterior tibialis, flexor digitorum communis and flexor hallucis longus tendons, which cross the sustentaculum tali inferiorly and contribute to dynamic stability of the hindfoot, could not be assessed in our study, which was limited to the intrinsic stability provided by osseous and ligamentous structures. Rather than a flaw, this could be seen as a validation of the study’s original goal, which was to assess the effect of ligament injury and whether reconstruction returned stability to near normal values, regardless of the role of dynamic stabilisers that would need to compensate for insufficient ligamentous stability. Another criticism to our study is that each cadaveric specimen is also the control of each technique. Using a separate control group would have increased the number of specimens needed. It was not possible to use pairs of ankles proceeding from the same cadaver, in which the technique could have been performed on one side with the other acting as a control. This disadvantage was tried to be minimised in this study using a logical sequence, analysing the intact joint as a control first, then progressively destabilising the joint and finally observing the effect of ligament reconstruction, before sectioning the extrinsic stabiliser of the subtalar joint.Second, the limitations inherent to the measurement technique must be mentioned. The force applied manually to perform the different manoeuvres was not measured. These manoeuvres are actually a dynamic measurement, and realistic reproduction of the clinical examination of instability would have been impossible it tensiometers had been used to control the forces used. Variability was tried to be reduced by having all the manoeuvres, repeated three times for each test, performed by single researcher, an orthopaedic surgeon with ample clinical experience in this area. The fact that the dynamic stabilisers are not reproduced must be added to the limitations of biomechanical cadaver studies.When progressively sectioning ligamentous stabilisers, significant values of angular displacement were measured with the inversion and eversion stress tests of the subtalar joint, two manoeuvres used in clinical practice but not evaluated to this level of detail, making this study clinically relevant. The ITCL was found to significantly add to subtalar joint laxity, and that joint kinematics against inversion were restored by allograft reconstruction of the ITCL, even in cases with a combined injury of the CL and ITCL.The ITCL was found to be an important stabiliser of the subtalar joint in the coronal and sagittal planes, in inversion as well as in eversion.The IER and the CL were stabilisers in the axial plane against inversion and eversion, respectively. Sectioning the CFL added to instability against eversion in the axial and coronal planes, and against inversion in the coronal plane.Reconstructing the ITCL using tendon graft significantly stabilised the subtalar joint in the axial and sagittal planes against eversion and in the axial and coronal planes against inversion, immediately after surgery.


Musculoskeletal disorders (MSDs) are a substantial societal burden and various factors affect their causation, recovery, and prognosis. Management of MSDs is complex and requires multifaceted interventions. Given the challenges of MSDs and their continued burden, it is possible that additional elements could impact these disorders that have not been fully researched, for example, indoor environmental quality. Our previous review provided preliminary evidence that healthy building determinants (HBDs) are associated with the risk of back and neck pain. However, the relationship of HBDs with extremity MSDs and general MSDs  has not been formally studied. The purpose of this review was to conduct a systematic literature review to assess the relationship of HBDs with extremity and general MSDs (PROSPERO ID: CRD42022314832). PubMed, CINAHL, Embase, and PEDRo databases were searched through April 2022. Inclusion criteria for study eligibility were as follows: humans of ages ≥18 years, reported on one or more of eight HBDs , and compared these HBDs with extremity MSDs or general MSDs, original research, English. Exclusion criteria were as follows: articles not published in peer-reviewed journals, full-text articles unavailable. Review procedures were conducted and reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. Empirical evidence statements were developed for 33 pairwise comparisons of HBDs with MSDs. The search uncovered 53 eligible studies with 178,532 participants. A total of 74.6% (39/53) of the studies were cross-sectional and 81.1% (43/53) were fair quality. Overall, the majority of uncovered evidence indicates that HBDs are related to risk of extremity and general MSDs. Nineteen comparisons support that as HBDs worsen, the risk of MSDs increases. Six comparisons had conflicting evidence. Three comparisons support that poor HBDs are not related to increased risk of extremity and general MSDs. Five comparisons had no evidence. This systematic review builds upon previous work to provide useful starting points to enhance awareness about the HBD-MSD relationship. These findings can help inform research and public health efforts aimed at addressing suboptimal HBDs through appropriate interventions to improve the lives of those suffering from MSDs. Musculoskeletal disorders (MSDs) are common, significantly impact the quality of life and physical abilities of individual sufferers, and are a substantial burden on society ,2. WhileMusculoskeletal disorders involve various connective tissues, such as bones, joints, muscles, tendons, and ligaments , across Various factors affect the causation, recovery, and prognosis of MSDs, and MSDs are causal agents themselves -12. FurtThe concept of healthy buildings is a "biopsychosocial framework that focuses on transforming the built environment to promote and enhance the health, wellness, performance, productivity, and quality of life of occupants," as we previously defined . The WorIt is plausible that addressing HBDs within the indoor built environment could be useful for addressing MSDs . FurtherOur 2022 systematic review examined the relationship of HBDs with spinal MSDs , which pMaterials and methodsOverviewThe current review incorporated similar methods, evidence synthesis procedures, and reporting structure as our earlier systematic review that examined HBDs and spinal MSDs . Taken tInformation SourcesThe search approach was adapted from our earlier systematic review that examined HBDs and spinal MSDs . StudiesEligibility CriteriaInclusion and exclusion criteria are depicted using the PICOTS method ,19.P - patient/people: Studies were included if they assessed humans of the ages 18 years and older with MSDs involving the extremity body regions or general body regions . The definition of MSDs is described elsewhere . Upper eI - intervention: Studies were included if they examined HBDs within the following eight categories: (1) air quality and ventilation, (2) dust and pests, (3) lighting and views, (4) moisture, (5) noise, (6) safety and security, (7) thermal health, and (8) water quality . While oPertinent definitions for this review are found elsewhere for healthy buildings ,16, builC - comparator: Studies were eligible for inclusion if they compared the previously described HBDs with extremity or general MSDs . The independent impact of the HBD on the MSD must have been assessed.O - outcomes/variables: Studies were included if they used various strategies to assess HBDs and MSDs, such as patient-reported, physical, functional, and environmental outcome measures. Studies were included that examined measures directly associated with MSDs, for example, disability and lost work time, while those that only examined outcomes indirectly related to MSDs, such as body mass, lifestyle, and psychosocial measures, were excluded .T - time/timing: Studies were included if they were published in peer-reviewed journals from database inception through April 15, 2022.S - setting: Studies were included if they assessed the previously described HBDs within the indoor built environment of commercial, public, residential, or work-related real estate settings. Studies were excluded that assessed outdoor environments .Additionally, studies were included if they were published in a peer-reviewed journal in English, human research, original research at the subject level, abstract was available for preliminary screening, and full-text article was available for the final determination processes. Studies were excluded if they were non-human studies , or grey literature, case reports, or reviews . StudiesData ExtractionStudy selection: Search results were handled using citation manager and spreadsheet databases . After pData extraction: JM extracted data from the eligible articles and entered them into the database, and EG separately cross-checked the results . Then, tOutcome measures: Since the uncovered evidence was mostly obtained from observational studies, the outcome variables measured in the eligible articles were mostly descriptive and relational .Data SynthesisApproaches adapted from the Oxford Centre for Evidence-Based Medicine, Clinical Information Access Portal -23, and Study quality and level of evidence: Study quality (risk of bias) was assessed using the NIH quality assessment instrument for observational studies . The insEvidence synthesis: Empirical evidence statements were synthesized based on strategies adapted from the Oxford Centre for Evidence-Based Medicine -23, AmerResultsStudy SelectionSearch results are found in the PRISMA diagram Figure . Fifty-tSixteen studies ,75,78,79Study CharacteristicsDetails of study characteristics and outcomes are shown in the Appendices. Overall, 178,532 individuals participated in the 53 included studies. Most studies (35/53) assessed workers in various occupational settings ,77-80,82Upper extremity MSDs were assessed in 32 studies ,79,80,84Various HBDs were assessed in the included studies as follows: air quality and ventilation (N = 16) ,77,79,83The studies were conducted in numerous countries as follows: Australia (n = 2) ,81, AustStudy OutcomesThe studies used various outcome measures for MSDs, including validated patient-reported outcomes  and administrative measures , as well as study-specific measures that have not been validated. Outcomes for HBDs were mainly study-specific and not validated for general use.Evidence Level and Study QualityStudy level and quality are shown in the Appendices. The evidence level of the uncovered studies was as follows: level 2  (n = 7) ,59,60,84Empirical Evidence StatementsEvidence was uncovered in support of significant relationships between many HBD categories and sub-categories with extremity and general MSDs as detailed in Table For upper extremity MSDs, weak evidence indicates that a positive relationship  exists between nine HBD categories and sub-categories , water quality, overall work environment), and upper extremity MSDs. Conflicting evidence was found for two HBDs . The evidence for lower extremity MSDs was mixed. Weak evidence indicates that a positive relationship exists between four HBD categories and sub-categories  and lower extremity MSDs. Weak evidence indicates that an inverse relationship exists between two HBD categories and sub-categories  and lower extremity MSDs. Conflicting evidence was found for three HBD categories and sub-categories . No evidence was found for two HBDs . For general MSDs, weak evidence indicates that a positive relationship exists between six HBD categories and sub-categories  and general MSDs. Weak evidence indicates that an inverse relationship exists between one HBD category  and general MSDs. Conflicting evidence was found for one HBD category (dust and pests). No evidence was found for three HBD categories and sub-categories .DiscussionGeneral InterpretationThe current systematic review found 53 studies on the relationship of several HBDs with extremity and general MSDs. More than 60% (32/53) of these studies were published over the last decade and were carried out in diverse countries, settings, and populations, thus the attention given to the HBD-MSD relationship is increasing. This review builds upon our previous work to provide useful starting points about the HBD-MSD relationship. These findings can enhance awareness and help inform future research and public health efforts aimed at addressing suboptimal HBDs through appropriate interventions to improve the lives of those suffering from MSDs .The awareness of the HBD-MSD relationship raised through the current review may also be useful to avoid unintended harm, particularly as the field progresses beyond its early stages. Healthy building initiatives evolved from prior efforts about the relationship between the built environment and human health, which typically have had a positive impact. However, sometimes these efforts had unintended consequences that created human harm. For example, attempts to improve the energy efficiency of buildings in the 1970s resulted in "sick building syndrome" (SBS) and its array of negative health consequences . The SBSEvidence from the current systematic review generally indicates that HBDs are related to risk of extremity and general MSDs. That is, poor HBDs are associated with increased risk of MSDs . Overall, the most consistent evidence in support of this statement was found for upper extremity and general MSDs, yet mixed evidence was found for lower extremity MSDs. When comparing the evidence across the various HBDs, consistent evidence supporting a positive relationship with higher risk of extremity and general MSDs was found for thermal health (cold), air quality and ventilation, thermal health (uncomfortable), moisture, safety and security, noise, and overall work environment. However, mixed evidence was found for dust and pests, lighting and views, thermal health (warm), and water quality.The findings of the current review, combined with our other review examining the HBD relationship with back pain and neck pain, provide a comprehensive initial assessment of the association of numerous HBDs with a wide range of MSDs . When coThe noted differences among the various musculoskeletal regions  and HBD categories and sub-categories  assessed in the current review are challenging to explain and require additional research. Possible explanations for these differences are factors inherent in the populations assessed. For example, most of the studies uncovered in the current review were conducted on workers whose primary job tasks involved relatively more upper extremity use compared to lower extremity. Thus, it is possible that the musculoskeletal regions required for a particular occupation may be most impacted by the built environment and the activity required within that environment.The level of studies uncovered in this systematic review limits the ability to conduct a full-scale causality assessment using Hill's criteria . NeverthAnother example of biological plausibility that may help explain the relationship between HBDs and MSDs is the association of environmental tobacco smoke with MSDs, as found in two studies of this review ,69. As nAnother explanation for the uncovered relationships is that HBDs are directly associated with other MSD risk factors that were not accounted for in the reviewed studies. For example, the current review and our previous review found that poor air quality was related to an increased risk of MSDs . In thisLimitationsThe current systematic review has limitations that are similar to our previous review, which preclude widespread generalizability . The uncImplications for Practice and PolicyWhile the field examining the HBD-MSD relationship is in its infancy, the findings of this systematic review are useful for future research, development, and public health efforts aimed at attenuating the negative impact of MSDs within the indoor built environment . These fFuture ResearchExpanding on the current review's findings through future research would be valuable to inform policy and practice, and foster implementation of interventions designed to positively impact the indoor built environment by augmenting HBDs and reducing MSDs . As detaMusculoskeletal disorders are a substantial societal burden and various factors affect their causation, recovery, and prognosis, which may include elements that have not been fully researched, such as indoor environmental quality. This review systematically examined the peer-reviewed literature on the relationship of eight HBDs with extremity and general MSDs. The search uncovered 53 eligible studies with 178,532 participants. A total of 74.6% (39/53) of the studies were cross-sectional and 81.1% (43/53) were fair quality. Overall, the majority of uncovered evidence indicates that HBDs are related to risk of extremity and general MSDs. Nineteen comparisons support that as HBDs worsen, the risk of MSDs increases. Six comparisons had conflicting evidence. Three comparisons support that poor HBDs are not related to increased risk of extremity and general MSDs. Five comparisons had no evidence. This systematic review builds upon previous work to provide useful starting points to enhance awareness about the HBD-MSD relationship. These findings can help inform research and public health efforts aimed at addressing suboptimal HBDs through appropriate interventions to improve the lives of those suffering from MSDs.


Autoimmune hemolytic anemia (AIHA) is a rare, very heterogeneous, and sometimes life-threatening acquired hematologic disease characterized by increased red blood cell (RBC) destruction by autoantibodies (autoAbs), either with or without complement involvement. Recent studies have shown that the involvement of T- and B-cell dysregulation and an imbalance of T-helper 2 (Th2) and Th17 phenotypes play major roles in the pathogenesis of AIHA. AIHA can be primary (idiopathic) but is more often secondary, triggered by infections or drug use or as a part of other diseases. As the location of origin of autoAbs and the location of autoAb-mediated RBC clearance, as well as the location of extramedullary hematopoiesis, the spleen is crucially involved in all the steps of AIHA pathobiology. Splenectomy, which was the established second-line therapeutic option in corticosteroid-resistant AIHA patients for decades, has become less common due to increasing knowledge of immunopathogenesis and the introduction of targeted therapy. This article provides a comprehensive overview of current knowledge regarding the place of the spleen in the immunological background of AIHA and the rapidly growing spectrum of novel therapeutic approaches. Furthermore, this review emphasizes the still-existing expediency of laparoscopic splenectomy with appropriate perioperative thromboprophylaxis and the prevention of infection as a safe and reliable therapeutic option in the context of the limited availability of rituximab and other novel therapies. Autoimmune hemolytic anemia (AIHA) is an acquired autoimmune disease characterized by the increased destruction of autologous red blood cells (RBCs) due to the presence of immunoglobulin (Ig)G, IgM, IgA, or complements usually C3d) bound to RBC membrane antigens ,2,3. Altd bound tShortened RBC survival due to hemolysis clinically manifests in symptoms which include weakness, dyspnea, jaundice, acrocyanosis or Raynaud phenomena, and splenomegaly, and laboratory tests reveal normocytic/macrocytic anemia, reticulocytosis, and elevated indirect (unconjugated) bilirubin and lactate dehydrogenase with reduced or fully consumed haptoglobin. The spherocytosis, agglutination, and polychromasia of RBCs can be seen in a peripheral blood smear. Hemoglobinuria and the presence of urinary hemosiderin indicate the onset of extravascular hemolysis .The severity of AIHA is determined by the type and affinity of autoantibodies (autoAbs), which reduce RBC lifespan, and by the capacity of bone marrow to compensate for hemolysis. A diagnosis of hemolytic anemia is issued when RBC survival drops below 100 days . The splThe diagnostic hallmark of AIHA is a positive direct Coombs test (antiglobulin test—DAT), and the classification of AIHA into warm AIHA (wAIHA) and cold AIHA (cAIHA) is based on the serological and thermal characteristics of the detected autoAbs. The most common type of AIHA is wAIHA, which accounts for 60–70% cases and is mediated by the autoreactive polyclonal IgG that binds to RBC antigens maximally at 37 °C. The most frequently occurring type of cAIHA, and the second most frequent type of AIHA , is cold agglutinin disease (CAD). CAD is mediated in 90% of patients by oligoclonal or clonal IgM autoAbs that maximally react at 4 °C and strongly activate complement due to their high density on RBC surfaces and the structure of IgM . A rare In 5–10% of patients with the laboratory characteristics of both wAIHA and CAD, the diagnosis of mixed-type AIHA is established . FurtherSimplified laboratory algorithms for AIHA diagnosis and the classification of AIHA are shown in It is important to notice that DATs may be negative in nearly 10% of patients with AIHA, predominantly those with wAIHA. This usually happens if the affinity and density of the autoAbs on the RBC surface is low , or because of the presence of IgA . On the AIHA is idiopathic (primary) in less than 50% of cases. In the remaining patients, the underlying diseases are identified, the most common being hematological malignancies, solid tumors, autoimmune and inflammatory diseases, and immunodeficiencies. A high incidence of AIHA is also observed in transplant recipients. AIHA can be triggered by acute and chronic bacterial and viral infections, including SARS-CoV-2, and numerous drugs . Of partHitherto, the pathogenesis of AIHA has not been fully understood. Today, it is believed that, as in autoimmune and lymphoproliferative diseases, the breakdown of immunological central and peripheral tolerance, T- and B-cell dysregulation, and a shift towards T-helper 2 (Th2) and Th17 phenotype play major roles in the generation of autoAbs directed against RBCs.The spleen is the largest secondary lymphoid organ and plays an important role in host defense but also in autoimmunity. The spleen is divided by function and structure into red and white pulp, with a perifollicular  zone in between. The primary immunological region of the spleen comprises white pulp, which occupies less than a quarter of splenic tissue. Unlike the lymph nodes, the spleen lacks afferent lymphatic vessels, and therefore, all cells and antigens enter the spleen via the blood . The secThe association between autoimmune disorders and neoplastic diseases, especially lymphoid neoplasms of B-cell origin (chronic lymphocytic leukemia(CLL), B-cell non-Hodgkin’s lymphoma, and Hodgkin’s lymphoma), was noted a long time ago. Autoimmune diseases, predominantly rheumatological , endocrinological , neurological (multiple sclerosis and myasthenia gravis), and dermatological (pemphigus vulgaris) ones, have been linked with various autoimmune cytopenias  and also with lymphoproliferative diseases and solid cancer. They share a common underlying etiology and are caused by the impaired self-tolerance of the immune system ,24,25,26KMT2D and mono-allelic CARD11 were demonstrated in patients with CAD. The loss of KMT2D function is related to the stimulation of the auto-reactive IGHV4-34-encoded immunoglobulin receptor, disturbed class switch recombination, and enhanced B-cell proliferation and survival. Mono-allelic CARD11 mutations result in B-cell proliferation and auto-antibody production. Similarly, oncogenic bi-allelic CARD11 mutations that result in constitutive nuclear factor (NF)-κB activation were demonstrated in a subset of patients with diffuse large B-cell lymphoma [The relationship between AIHA and congenital conditions such as common variable immunodeficiency/hyper IgM syndrome/autoimmune lymphoproliferative syndrome/Kabuki syndrome suggest that genetic background is an important factor regarding AIHA onset. Recurrent somatic mutations of lymphoma .Conversely, the origins of autoAbs in drug-induced AIHA (DIHA) are well established. More than 160 drugs are suspected of inducing AIHA, the most commonly reported being antibiotics , antimycotics (fluconazole and amphotericin B), diclofenac, ibuprofen and other non-steroidal anti-inflammatory drugs, immunosuppressive (azathioprine) and antineoplastic drugs , cardiovascular drugs , and many others, including corticosteroids ,29,30. IAlthough an adaptive immune response to foreign antigens is initiated in the white pulp, immune effector function takes place and expands in spleen red pulp where neutrophils, monocytes, dendritic cells (DCs), gamma delta (γδ) T cells, and macrophages reside . The mosExtravascular FcγR-mediated hemolysis takes place in the spleen and lymphoid organs. Spleen macrophages regulate RBC turnover in physiological and pathological circumstances. During a normal lifespan, RBCs encounter detrimental changes in plasma cell membrane and become less deformable. Senescent RBCs are too rigid to pass through the inter-endothelial slits of the spleen red pulp, and those trapped RBCs are phagocytized by macrophages located in the cords of the red pulp. Every day, approximately 1% of aged and irreversibly damaged RBCs are removed from circulation . Besides2 transport, to mediating phagocytosis in the spleen. Namely, Band 3 exposes neoantigens that are recognized by naturally occurring Abs (Nabs) and cleared by macrophages. Conversely, CD47 represents one of the “do not eat me” signals, and binding to its receptor, signal-regulatory protein alpha (SIRPα), on macrophages suppresses phagocytosis by inhibiting the inside-out activation of integrin signaling [The most abundant integral membrane protein in RBCs is Band 3 (SLC4A1), with more than a million copies per cell. Band 3 is associated with a number of other membrane proteins including the Rh complex, glycophorins, and CD47. At the inner RBC membrane, Band 3 is attached to the cytoskeleton through interaction with ankyrin, while its carboxyl terminus is associated with carbonic anhydrase. Consequently, Band 3 has numerous fundamental functions in maintaining RBC integrity—from controlling RBC shape and deformability, through regulating COignaling . In wAIHignaling . Spleen ignaling .Splenic macrophages possess three types of FCγR receptors for the IgG heavy chain that activates phagocytosis: FcγRI (CD64), FcγRIIA (CD32a), and FcγRIII (CD16). Phagocytosed RBCs are targeted to phagolysosomes. FcγRI has the highest affinity for IgG molecules, and its activation induces signaling pathways. This includes phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAP), which are responsible for efficient erythrophagocytosis and a minimal release of harmful free hemoglobin into circulation. It is of clinical interest that spleen macrophages also express an inhibitory FcγRIIB and that its activation may explain the inefficiency of intravenous Ig (IVIG) in wAIHA as their therapeutic activity is mediated through binding to FcγRIIB .Besides phagocytosis, spleen macrophages can only remove the IgG-coated portion of RBC membranes, resulting in a change in shape and RBCs becoming deformable. The formed rigid microspherocytes are retained in spleen red pulp sinusoids and cleared, as previously explained. Spleen CD8+ T cells and NK cells that also express FcγR are responsible for the ADCC destruction of opsonized RBCs ,5,23,35.The pivotal role of the spleen in the immunological background of AIHA is illustrated in The presence of reticulocytopenia instead of reticulocytosis is not uncommon as a sign of insufficient erythropoiesis and poor prognosis. Indeed, this is observed in 20–40% of AIHA cases . It has 6 RBCs per second. The production of RBCs is in tight balance with the turnover of senescent RBCs by red pulp macrophages in the spleen [It has been estimated that adult humans make more than 2.5 × 10e spleen ,43. Paule spleen . In aneme spleen ,46. TLR4e spleen . Howevere spleen . The rece spleen .Gata1, Tal1, and Klf1). Conversely, genes involved in the immune response were inhibited, and NK cells decreased during stress erythropoiesis [Besides the removal of aged, dead, or opsonized RBCs from circulation, spleen red pulp serves as a reservoir of RBCs, with the capacity to store 15–25% of total RBC volume that can be ejected as a physiological response to hypoxia  . Furtheropoiesis . ExtrameCurrent guidelines recommend glucocorticoids and rituximab for first-line therapy . TransfuSpecific first-line treatment strategies for AIHA are based on the inhibition of autoAb production. Patients with newly diagnosed symptomatic wAIHA (Hb level ≤ 100 g/L) are recommended to take oral prednisone 1 mg/kg daily. In steroid-responsive patients, i.e., those whose Hb rises above 100 g/L, the taper can begin after 2–3 weeks. If the dose can be reduced to 7.5 to 10 mg per day after 3 to 6 months without the relapse of clinically significant anemia, a further tapering should be attempted until the drug is discontinued. In the case of long-term corticosteroid treatment, patients should also receive treatment to prevent osteoporosis and fragile fractures  ,32,54,552 weekly for 4 weeks) or at a low dose (100 mg weekly for 4 week) and combined with corticosteroids [In patients with wAIHA who do not respond to corticosteroids, in those who relapse during corticosteroid tapering or after discontinuation, and in those requiring unacceptably high doses >10–15 mg daily), the introduction of rituximab is recommended. It is important to emphasize that a lack of response to corticosteroids is suggestive of secondary wAIHA and indicates further investigation. Rituximab is a chimeric human IgG1-κ mAb directed against the extracellular domain of protein CD20, which is expressed on B-cells. Initially approved for the treatment of B-cell non-Hodgkin’s lymphoma, Rituximab has proven to be safe and effective therapy for the treatment of primary and secondary wAIHA ,58,59,60 mg dailysteroids ,61. The steroids .Better insights into the pathobiology of AIHA have encouraged the investigation of numerous agents used to inhibit immune responses at various stages. Most of them are already approved for other indications. For example, rozanolixumab, the inhibitor of neonatal Fc receptor (FcRn), shortens IgG half-life from a normal 28 days to about 10% and is currently approved for the treatment of myasthenia gravis; fostamatinib , the splDrugs that target LLPCs include bortezomib, a proteasome inhibitor that is already included in recommendations for the treatment of cAIHA  and in rThe enlargement of spleen in AIHA is the consequence of Ab production, the immune destruction of RBC, and extramedullary hematopoiesis, crucial factors in IHA pathobiology. The surgical removal of the spleen was recognized and widely accepted as an effective therapeutic option in corticosteroid-resistant AIHA cases a long time ago. In a study by Allgoold and Chaplin on 44 AIHA patients published in 1967, an early response was obtained after splenectomy in 68% of corticosteroid-resistant patients, and 44% were able to maintain remission without supplementary steroid therapy after more than one year post-splenectomy. On the other side, the long-range mortality rate in this cohort was 40%, and the most common cause of death was pulmonary embolism . ExcelleIn the years that followed, although still prior to the introduction of novel therapy in the treatment of AIHA and underling diseases, the reported median time from AIHA diagnosis to splenectomy extended and the laparoscopic procedure prevailed over the open-surgery technique ,100. DueThe introduction of rituximab was a turning point in the treatment of AIHA and gave impetus to the use of a wide range of innovative drugs in the treatment of AIHA, relegating splenectomy to the third and subsequent therapeutic lines ,106,107,In addition to the abovementioned study conducted by Serbian authors, which compared the safety of laparsacopic and open techniques , by searAccording to the current guidelines, splenectomy or partial splenic embolization are still recommended in the emergency management of transfusion-dependent life-threatening wAIHA that is unresponsive to prednisolone. This should be combined with other supportive therapies (erythropoietin stimulating agents (ESA) and/or plasma exchange and/or IVIG) and active immunosuppression ,55.The loss of crucial functions of splenic macrophages in eliminating encapsulated bacteria and prolonged antecedent or concomitant immunosuppression renders splenectomized AIHA patients highly susceptible to bacterial infections, with a reported rate of 6–7% . Among tThromboprophylaxis is also indicated in splenectomized AIHA patients in order to minimize the risk of venous thrombosis. It has long been recognized that AIHA has a prothrombotic state, per se , and thrSplenectomy is not recommended to treat complement-mediated intravascular hemolysis, nor is it recommended for complement-mediated extravascular hemolysis where CD3b-opsonized RBCs are destroyed via liver macrophages that carry receptors for C3b fragments . This isThe spleen is the location of origin of autoAb and the location of antibody-mediated RBC phagocytosis in AIHA, as well as the location of extramedullary hematopoiesis. Splenectomy was the therapeutic option in corticosteroid-resistant AIHA patients for decades. In the era of modern therapy, splenectomy is scarcely performed, as it is either employed as a third or subsequent line of treatment or is recommended as a rescue management technique for transfusion-dependent, life-threatening wAIHA. The reported rate of complications following splenectomy has gradually decreased over time due to less invasive laparascopic techniques, vaccination against encapsulated bacteria, and thromboprophylaxis. Today, splenectomy is not associated with increased mortality. When taking into account this and the real-world evidence of the limited wide availability of rituximab and other costly targeted therapies inspired by clinical trials in most and not only developing countries, laparascopic splenectomy holds its place as a safe and good therapeutic option in the selected pools of AIHA patients.


The number of wearable technological devices or sensors that are commercially available for gait training is increasing. These devices can fill a gap by extending therapy outside the clinical setting. This was shown to be important during the COVID-19 pandemic when people could not access one-on-one treatment. These devices vary widely in terms of mechanisms of therapeutic effect, as well as targeted gait parameters, availability, and strength of the evidence supporting the claims.This study aimed to create an inventory of devices targeting improvement in gait pattern and walking behavior and identify the strength of the evidence underlying the claims of effectiveness for devices that are commercially available to the public.As there is no systematic or reproducible way to identify gait training technologies available to the public, we used a pragmatic, iterative approach using both the gray and published literature. Four approaches were used: simple words, including some suggested by laypersons; devices endorsed by condition-specific organizations or charities; impairment-specific search terms; and systematic reviews. A findable list of technological devices targeting walking was extracted separately by 3 authors. For each device identified, the evidence for efficacy was extracted from material displayed on the websites, and full-text articles were obtained from the scientific databases PubMed, Ovid MEDLINE, Scopus, or Google Scholar. Additional information on the target population, mechanism of feedback, evidence for efficacy or effectiveness, and commercial availability was obtained from the published material or websites. A level of evidence was assigned to each study involving the device using the Oxford Centre for Evidence-Based Medicine classification. We also proposed reporting guidelines for the clinical appraisal of devices targeting movement and mobility.The search strategy for this consumer-centered review yielded 17 biofeedback devices that claim to target gait quality improvement through various sensory feedback mechanisms. Of these 17 devices, 11 (65%) are commercially available, and 6 (35%) are at various stages of research and development. Of the 11 commercially available devices, 4 (36%) had findable evidence for efficacy potential supporting the claims. Most of these devices were targeted to people living with Parkinson disease. The reporting of key information about the devices was inconsistent; in addition, there was no summary of research findings in layperson’s language.The amount of information that is currently available to the general public to help them make an informed choice is insufficient, and, at times, the information presented is misleading. The evidence supporting the effectiveness does not cover all aspects of technology uptake. Commercially available technologies help to provide continuity of therapy outside the clinical setting, but there is a need to demonstrate effectiveness to support claims made by the technologies. Gait is one of the most frequently assessed attributes in clinical settings because gait impairment is the hallmark of several different health conditions ,2. Prevaownership over their therapy [Effective and accessible treatments for gait impairments will increasingly be needed with the aging of the population and as people with health conditions live longer. Skilled therapy professionals are a limited resource, and therapy is rationed; furthermore, rehabilitation is a global target of the World Health Organization’s 2030 strategy, with key areas for action to increase affordable services and use technology to address this need to assess and reassess how individuals mobilize and move and implement long-term training programs . Increas therapy . There i therapy ,26. ThesAvailable devices range in sophistication from nonelectronic shoe insoles and walking aids to inertial or pressure sensors. Most of the technologies used have gait assessment functionality, but there is now increasing interest in harnessing the capacity of wearable sensors for providing biofeedback. The literature is rich in supporting the effectiveness of biofeedback in improving gait patterns in healthy and clinical populations -30.There is an increasing number of devices that claim to improve gait impairments through biofeedback. However, it is still rare for these devices to be available to the consumer; most are still tied to a laboratory setting. There is an urgent need to move technological innovations from research laboratories to the people who would benefit the most—those with gait impairments. The COVID-19 pandemic has alerted us to the vulnerability of seniors and people living with chronic health conditions when they were no longer able to access clinical and community resources -37. In aThe market of people needing gait training technologies is huge. As a result of direct access of the general public to several technologies, the impact of evidence presented on the websites could affect purchasing behavior. A study on the purchasing intention of consumers who shop on the web found that “high involvement” consumers, defined as people living with health conditions who need to improve their gait to meet functional demands or mobility needs and are intently looking to purchase something specific, were more likely to purchase a product if the number of quality reviews was high . IndividGait training technologies must be appealing with features such as product attractiveness, functionality, and price, as well as be supported by robust research demonstrating usability, reliability, efficacy, and effectiveness. All these features are equally important; an attractive product that does not work or a product that does work but is expensive would not be appealing. Although the attractiveness of technologies is often featured on websites, the evidence for efficacy could be hard to locate. Furthermore, the public is not likely to have access, time, or training to find the scientific literature and critically appraise the content to guide the decision to purchase such products.The objectives of this customer-centered review were to create an inventory of devices targeting improvement in gait pattern and walking behavior and identify the strength of the evidence underlying the claims of effectiveness for devices that are commercially available to the general public .As there is no systematic or reproducible way to identify technologies available to the public to help improve gait, we used a pragmatic and iterative approach. Our search strategy involved a search of gray literature as well as published literature. A findable list of technological devices targeted to health conditions was extracted separately by 3 authors and compared for completeness. For each device identified, the evidence for efficacy or effectiveness was extracted from material displayed on the websites, and full-text articles were obtained from the scientific databases PubMed, Ovid MEDLINE, Scopus, or Google Scholar. This step was carried out by MM, AA, MW, OS, SG, DG, and HD; any conflicts were resolved in consultation with KM and AA-S. Finally, KM and NEM organized the results into tables and reverified all data and assigned levels of evidence. A level of evidence was assigned to each study involving the device using the Oxford Centre for Evidence-Based Medicine scale ,47.levels of evidence rating system is a method of quantifying the best clinical evidence that is available about the efficacy and safety of treatment approaches that are destined to be implemented in clinical care [The cal care ,47. The feedback is defined as a physiological or performance signal arising as a result of human movement that, in turn, generates an output (error or correct performance) that is relayed back to the user and that has the potential to modulate (enhance or diminish) subsequent movement.Information on the target population, mechanism of feedback, evidence for efficacy or effectiveness, and commercial availability was obtained from the published material or websites. Only devices that claimed gait rehabilitation or gait quality improvement through any sensory feedback mode—visual, auditory, haptic (tactile or kinesthetic), or vibration—were included. The devices were excluded if the technology was not targeted to any health condition or if it targeted high-functioning populations such as athletes or healthy individuals. The term The search yielded 17 wearable devices that claimed to target improvement in gait quality through various types of feedback: 11 (65%) were commercially available, and 6 (35%) were at various stages of research and development. Of the 11 commercially available devices, 2 (18%) were sold under the trademark WalkWithPath: Path Finder Laser Shoes and Pathfeel. The inclusion of the devices was appraised by KM and NEM. BalancePro Authors, year: Jenkins et al , 2009Population: individuals with Parkinson disease, n=40: 16 women and 24 men; age-matched controls, n=40: 25 women and 15 menIntervention: facilitatory shoe insoleControl: conventional flat insoleOutcome: spatiotemporal gait parameters measured using GAITRite mat and muscle activity measured using electromyography (in 20 people with Parkinson disease and 20 controls)Time: concurrent trialsTraining: 10 walking trials: 5 with facilitatory insoles and 5 with conventional insolesResults: group effect on velocity, step length, and step length variabilityUsability: not reportedLevel of evidence, study design: 2b, crossover (website and PubMed)Authors, year: Maki et al , 1999Population: older adults, n=14: 6 women and 8 men; 7 healthy controlsIntervention: modified insolesControl: noneOutcome: center of mass displacement and stepping reactions using force platesTime: concurrent trialsExperimental condition: multiple transient perturbations and continuous perturbations: 40 and 16, respectively, for older adults and 56 and 24, respectively, for controlsResults: facilitation reduced the number of forward step reactions to perturbationsUsability: not reportedLevel of evidence, study design: 2b, crossover (website and PubMed)Authors, year: Perry et al , 2008Population: older adults, n=40: 19 women and 21 men aged 65 to 75 yearsIntervention: facilitatory insoleControl: conventional insoleOutcome: lateral displacement of center of mass in relation to base of support during single-support phaseTime: 12 weeksTraining: 12 trials on 4 uneven surfaces wearing each soleExperimental: 12 weeks of wearing randomly assigned soleResults: outcome effect for 2 of the 4 uneven surface conditionsUsability: lower fall rate in intervention (25% vs 45%); mild discomfort occurrences reported for 17 out of 240 wear-weeks; 17 out of 20 participants would continue wearingLevel of evidence, study design: 2b, randomized trial (website and PubMed)Walk With Path Authors, year: McCandless et al , 2016Population: individuals with Parkinson disease, n=20: 14 men and 6 women; mean age 68 years; independently ambulatory indoors, with freezing of gaitIntervention: laser cane, sound metronome, vibrating metronome, and vibrating walking stickControl: no cueingOutcome: frequency of freezing of gait episodes over 3-meter walk, first step length, second step length, forward center of mass velocity, sideways center of mass velocity, number of forward and backward sways and number of sideways sways, and forward center of pressure velocity (meters per second) and side-to-side center of pressure velocityTime: concurrent trials, 3 per device and 3 control Training: noneResults: 12 out of 20 participants contributed 100 freezing and 91 nonfreezing trials; laser cane was most effective for freezing of gait and for movement strategies to reinitiate movement, whereas vibrating walking stick was second most effective; vibration metronome disrupt movement compared with the sound metronome at the same beat frequencyUsability: not reportedLevel of evidence, study design: 2b, crossover (website and PubMed)Authors, year: Barthel et al , 2018Population: individuals with Parkinson disease with freezing of gait, n=21: 5 women and 15 men Intervention: visual cueing using laser shoesControl: no cueingOutcome: duration and number of freezing of gait episodesTime: concurrent trials, 5 trials each during on medication and off medication periodsTraining: (1) walking back and forth over 10 meters; (2) task 1 plus counting down from 100 in steps of 7 or 3; (3) turning on command while walking, including 180° and 360° right and left turns; (4) walking to pick up a cone at 7 meters and then back carrying the cone; and (5) walking around obstacles placed on the walkwayResults: cueing reduced the number of freezing of gait episodes, both off (45.9%) and on (37.7%) medication, reduced the percentage of time frozen during the off period by 56.5% (95% CI 32.5-85.8), and reduced the percentage of time frozen during the on by 51.4% (95% CI –41.8 to 91.5)Usability: not reportedLevel of evidence, study design: 2b, crossover (website and PubMed)Authors, year: Velik et al , 2012Population: individuals with Parkinson disease with freezing of gait, n=7: 1 woman and 6 menIntervention: 3 cueing conditions: no cue, visual cue on for 10 seconds whenever freezing occurred, and continuous visual cueControl: no cuesOutcome: average duration and number of freezing episodes under 3 conditionsTime: concurrent trialsTraining: 6 tasks to be performed: (1) standing up from a chair and getting a glass of water from the kitchen, (2) going with the glass of water to the bathroom and leaving it on the washbasin, (3) walking to the bedroom and picking up a clothes hanger from the cupboard, (4) carrying a clothes hanger to the washing room and leaving it there, (5) going back to the chair, and (6) performing tasks 1 to 5 in reverse order, starting with task 5Results: continuous cueing: mean duration of freezing reduced by 51%, with 43% fewer freezing of gait episodes; on-demand cueing: mean duration of freezing reduced by 69%, with 9% fewer freezing of gait episodesUsability: not reportedLevel of evidence, study design: 2b, crossover (website and PubMed)Heel2Toe Authors, year: Mate et al , 2020Population: older frail and prefrail persons, n=6: 4 women and 2 menIntervention: supervised training with the Heel2Toe sensor, 5 sessions over 2 weeksControl: noneOutcome: spatiotemporal gait parameters and system usabilityTime: immediate and posttest feedback; end of training without and with feedbackTraining: supervised gait training and walking practice with the Heel2Toe sensor providing feedback for good steps; prescription of 5 exercises, 1 per walking componentResults: immediate and posttraining response: 5 of the 6 participants displayed meaningful changes in terms of good steps, angular velocity, and coefficient of variation, whereas 1 high-functioning person showed no changeUsability: 38-item responses: 25/38 (66%) were at optimal levels, and 9/38 (24%) were at the poorest levelsLevel of evidence, study design: 2b, sequential pretest-posttest design (website and PubMed)Authors, year: Carvalho et al , 2020Population: individuals with Parkinson disease, n=6: 4 women and 2 menIntervention: supervised training with the Heel2Toe sensor, 5 sessions over 2 to 3 weeksControl: noneOutcome: spatiotemporal gait parameters and system usabilityTime: immediate pretest and posttest feedback; end of training without and with feedbackTraining: supervised gait training and walking practice with the Heel2Toe sensor providing feedback for good steps; prescription of 8 mobility exercisesResults: immediate and posttraining response: of the 6 participants, 3 displayed meaningful changes in terms of good steps, 4 improved on angular velocity, and 1 reduced coefficient of variationUsability: 24-item responses: 17/24 (71%) were at optimal levels, and 9/24 (37%) were at the poorest levelsLevel of evidence, study design: 2b, randomized clinical trial (website and PubMed)CuPiD/Gait Tutor Authors, year: Ginis et al , 2016Population: individuals with Parkinson disease, n=40: 8 women and 30 men independently ambulatory for at least 10 minutes, with freezing of gaitIntervention: supervised weekly visits for 6 weeks plus recommendation to walk at least 3 times per week for 30 minutes with feedback and cues provided separatelyControl: walking training with no feedbackOutcome: gait speed, stride length, and double support time for comfortable gait and dual-task gait conditions; balance evaluated using Mini Balance Evaluation Systems Test; Four Square Step Test; Falls Efficacy Scale-International; 2-minute walk test; freezing of gait; Unified Parkinson’s Disease Rating Scale, part III; cognition; and quality of lifeTime: pretest-posttest training (6 weeks) and retention (4 weeks)Training: weekly home visits for 6 weeksResults: single-task and dual-task gait speeds improved within group at posttest and follow-up assessments; intervention group improved on balance at posttraining assessmentUsability: not reportedLevel of evidence, study design: 2b, randomized clinical trial (website and PubMed)Authors, year: Ginis et al , 2017Population: individuals with Parkinson disease, n=28: 5 women and 23 men; 14 age matchedIntervention: 4 walks  over 6 weeks with at least 1 week between walksControl: no informationOutcome: cadence, stride length, and fatigueTime: concurrent trialsTraining: comfortable 1-minute reference walk before testingResults: decrease in cadence in participants with Parkinson disease without cues or feedback; participants with Parkinson disease reported more fatigue with continuous cueing and intelligent feedback; increase in coefficient of variation in cadence in participants with Parkinson disease; and less variation in cadence with continuous and intelligent cueing in participants with Parkinson diseaseUsability: reportedLevel of evidence, study design: 2b, crossover (website and PubMed)Problem to be addressed: gap that the technology is fillingFunctionality: assessment, treatment, or bothTechnology type: implant, robot, exoskeleton, biosensors, virtual or augmented reality, assisted living technologies, wearables, smart devices, trackers, remote monitoring, and chatbotsTechnology: describe in a way that it can be pictured without an imageLevel of technology: technology readiness level (levels 1 to 9) Population: (1) health condition and special selection criteria and (2) level of technology readinessTechnology: country-specific regulatory authority classification of the medical device; mechanism of action: actual or hypothesized; reliability of algorithm used in the technology; and comparability with existing methods: (1) comparing assessments: competing technologies and (2) comparing treatments: sham, nothing, usual care, alternative form of technology, alternative intervention, and attention controlExperimental protocol: as per Consolidated Standards of Reporting Trials (CONSORT) or other reporting guidelines  or as peOutcomes: biofunctional model linking the technology to proximal and distal outcomes:Proximal (explanatory) outcomes: technological metrics and impairment level from the patient’s perspectivePrimary (confirmatory) outcomes: clinically assessed activity outcomes (capacity)Distal (exploratory) outcomes: real-world assessed activity outcomes (performance) and health-related quality of lifeSource of information: patient-reported outcomes, self-reported outcomes, performance outcomes, and technologically assessed outcomes Results: as per CONSORT or other reporting guidelines; distributional parameters presented for every outcome, every time point, and every transitionSafety: symptoms (new or aggravated), allergies, injuries, abrasions, and fallsUser experience: qualitative and quantitative information on positive and negative experiences with the technology; actions taken to remedy negative experiencesUsability: quantitative measure of perceived usabilityAdoption: data on short-term update and data on long-term useLevel of evidence: level of evidence classification system specifiedThis review identified a total of 17 wearable biofeedback devices targeting gait patterns and walking behavior. Of these 17 devices, 11 (65%) are commercially available to the public and have a dedicated website for direct purchase. Of these 11 devices, 4 (36%) had published evidence on effectiveness at level 2b according to the Oxford Centre for Evidence-Based Medicine scale . There wThis review provides a summary of commercial wearable gait training technologies that are currently available in the market or the development phase. A unique feature of this review is that it was conducted from a consumer’s perspective and then augmented by summarizing the evidence from scientific publications. Although the strength of the evidence supporting the effectiveness of these technologies is low or moderate at best, the claims on the website often outweigh the evidence. The results of our review can also be used by professionals involved in gait rehabilitation to direct their clients to promising technologies based on available evidence. These technologies can also be incorporated into treatment plans.P values rather than CIs. Lack of raw data in the published manuscripts, such as mean, median, SD, and range, prevented a calculation of between-group effects, effect sizes, and reliable change among other metrics that can potentially provide more interpretable information. Sample sizes are typically small, leading to a high degree of uncertainty in the results. Very few papers  reported information on missing data or steps taken to account for missing data and the potential impact on the conclusions.Several of the papers  that contributed evidence toward the efficacy and effectiveness of the wearable sensors failed to capture or report patient-centered outcomes or declared level of evidence. In summary, the quality of evidence was low. Only 36% (4/11) of the devices had searchable evidence for efficacy potential, with all studies being small-sample sized . This casocial listening service Awario that searches social media platforms  and the web for investigator-selected keywords [snowball sampling where systematic reviews served as the source, and the web was searched for any devices named in these reviews.There is a challenge in searching for information on technology. A 2022 review evaluated the type and quality of information available on the web for aquatic physiotherapy targeted to people with Parkinson diseases . The autkeywords . The strscam people into buying products that are possibly noneffective or even harmful and that clear reporting standards for consumers are made mandatory for these technologies, similar to those now standard for food.Many commercial technology companies reported ≥1 clinical trials that are underway; yet, there is a lack of trial-specific information. A potential consumer is unlikely to track these details. It is important to consider the transparency and accessibility of scientific evidence when making evidence-based recommendations to consumers. There is limited research in this area, specifically from a consumer’s perspective. Although there is a need to provide therapy outside clinical settings, it is critical that companies marketing technologies do not gold standard for rigorous, systematic gray literature search methods, and there are few resources on how to conduct this type of search; for example, the Cochrane Handbook, often cited as the gold standard for conducting systematic reviews, provides limited guidance and specificity for gray literature search methods [The approach taken here may not have yielded complete results, and, because new technologies are continually developed and added to or removed from the market, the results can quickly become out of date. Many technologies are developed in research settings and are not given a proprietary name until there is evidence to support commercialization. Hence, searching for earlier information is impossible. In addition, the inventors, the authors of the papers, and the entrepreneurs commercializing the technology may not be the same people; hence, an author search will also be fruitless. CuPiD/Gait Tutor is an example of a name change ,65. Fina methods . In addiTherefore, the findings of this review are only valid based on the search conducted at the time. Given the difficulty in searching for gait training technologies, the search method reported here may be difficult to reproduce. Nevertheless, the information presented on the technologies discovered in this search uncovers existing gaps in the evidence and the reporting.As newer technologies for gait training are continually developed, it is important that the evidence supporting their efficacy and effectiveness is quickly made available to people to make an informed choice. Often, the published literature is unavailable to the general population because of journal paywalls. There was also a lack of consistency in reporting information related to usability, safety, or user feedback. Standards for reporting on research involving technological devices, in the form of reporting guidelines, seem to be a critical need to ensure that the data needed by the potential consumer are communicated.There are several reviews on the efficacy and effectiveness of gait training technologies. One objective of the research is to build capacity and empower patients who wish to take charge of their health. By equipping people living with gait impairments with the opportunity to improve walking outside clinical settings through biofeedback is a step in the right direction, given the limited access to rehabilitation services. A few technological innovations were initiated along the commercialization path but were abandoned at different stages. Despite the many benefits of at-home therapy, some challenges exist, including device maintenance, battery life, and technological literacy. One study suggests that the most effective devices are those that have a “user-centered design,” meaning patients or practitioners are involved in the design process . Many ofAlthough there is strong interest from academic institutions and government agencies to transfer technologies from laboratories to clients, there is a need for due diligence on the part of both the institutions and industry to accurately report all the findings that not only support the science but will also influence a client’s or an organization’s decision to purchase the technology.Research in the field of technology development seems to lack the rigorous research method standards required for drug testing, allowing some devices to enter the market based mainly on safety rather than efficacy. Almost all commercial devices overclaim the efficacy of the technology to other populations not supported by their research; for instance, a website will claim effectiveness for people with gait impairments when the device was tested only in people with Parkinson disease. Finally, it would truly benefit the general public to have a summary of the research in layperson’s terms similar to food standards.The field of technology evaluation would benefit from reporting guidelines to extend the guidelines for reporting on randomized clinical trials , such as are available for many different types of experimental studies, including pilot and feasibility studies and crossover designs, all of which can be found on the Enhancing the Quality and Transparency of Health Research (EQUATOR) website . There aThis review is the first of its kind from a consumer’s perspective that critically appraises wearable biofeedback gait devices found on the internet, the literature available on the respective websites, and the strength of evidence supporting the claims. The review highlights the need for providing standardized reporting of device capabilities as information accessible to the public when marketing commercialized devices. This review provides the public and health care practitioners with a summary of information that can be used to choose wearable biofeedback gait technologies or decide not to adopt them. The review covers 17 wearable devices that provide 1 form of feedback to improve gait and outlines the mechanisms claimed to underlie gait improvement. There was no predominance for biofeedback type . A variety of biofeedback modes have been used , with auditory and vibratory haptic being the most common. The strength of the evidence supporting these devices from scientific sources was at 2a  or 2b  level. Gaps in reporting all needed information for the consumer were uncovered. The propensity of small trials and heterogeneity of studies and conditions highlight the requirement for standardizing reporting of feedback intervention measures and doses to enable meta-analyses to move gait technological rehabilitation forward. Of note, there is a lack of evidence for motor learning interventions even in the field of sport, with a need for current evidence to be extended by theory-driven, high-quality studies to allow for more consolidated and evidence-based recommendations. Technology has the potential to advance the rehabilitation space and enable a better understanding of optimal interventions for learning and maintaining skills. Taken together, our findings target the need for clear reporting standards for gait interventions.