Early implementation of MAK robotic device in total knee arthroplasty rehabilitation: A proof-of-concept study.

BACKGROUND: Effective rehabilitation following total knee arthroplasty (TKA) is crucial for enhancing both range of motion (ROM) and functional outcomes. While robotics has demonstrated its potential in various medical contexts, the evidence on its application in TKA rehabilitation is still scarce. The marsi active knee (MAK), a robotic device that has already proven to be safe and beneficial in people with neurological disease, has been tested to facilitate the rehabilitation of TKA patients. OBJECTIVE: This study aims to evaluate the safety, patient satisfaction, and clinical impact of integrating the MAK into an early rehabilitation regimen for TKA patients. METHODS: The intervention comprised 14 one-hour sessions administered thrice a week, utilizing the MAK within 48 h post-TKA surgery. The rehabilitation sessions incorporated exercises involving passive mobilizations, sit-to-stand transitions, and gait training. Comprehensive data encompassing safety parameters, patient satisfaction, and clinical outcomes were meticulously collected and analyzed. RESULTS: Six participants successfully completed the rehabilitation protocol with the MAK device. Notably, no significant adverse events were documented. Application of the device corresponded to perceptible reductions in self-reported pain levels. Vital signs remained within minimal variance pre- and post-rehabilitation. Participants proficiently engaged in all assisted exercises facilitated by the device, culminating in a high overall satisfaction rating of 4.6 ± 0.5 out of 5. CONCLUSION: The findings indicate that the MAK device exhibits a commendable level of safety while obtaining considerable patient satisfaction during the early rehabilitation phase following TKA, suggesting this device may be a reliable adjunct to TKA protocols.

Safety and usability of the MAK exoskeleton in patients with stroke.

BACKGROUND AND PURPOSE: Stroke is one of the leading causes of disability in adults worldwide, and one of the main objectives in the rehabilitation of these patients is to recover the gait. New technologies have emerged to cope with this issue, complementing conventional therapy with the use of devices such as exoskeletons. The Marsi Active Knee (MAK) exoskeleton (Marsi Bionics SL, Madrid, Spain) has already been tested, but an updated version was improved to allow the patients to perform functional exercises. The aim of this study was to assess the safety and usability of the MAK in the stroke population as well as its potential clinical effects. METHODS: A single-group open label intervention trial was conducted. The device was used twice a week for 5 weeks during 1 h per visit. During the visits, sit-to-stand transitions, walking, stair climbing, trunk rotations, and weight-transfer exercises were performed using the device. Adverse events were collected from participants and therapists to assess safety. The Quebec User Evaluation of the Satisfaction with assistive Technology (QUEST 2.0) was used by both therapists and participants to assess usability. To evaluate its clinical effects, active range of motion (ROM) and muscle strength were assessed in the lower limb. RESULTS: Six participants with stroke were recruited. The device was shown to be safe since no serious adverse events were reported neither by patients nor by therapists. Every proposed exercise was performed. Regarding clinical effects, overall muscle strength showed an increase after the treatment, although ROM measurements did not show any difference. DISCUSSION: Our results suggest that the MAK device is safe for stroke patients. Nevertheless, further changes to enhance usability are recommended, such as an improvement of the attachment system and an adaptation for the drop foot. Beneficial effects regarding increases in muscle strength were obtained. Further trials with a larger sample size, longer intervention periods, and a control group are needed to verify these results. Also, future research should focus on the usability of the MAK as an assistive technology.

Prevalence of specific antibody to hepatitis E virus in the general population of the community of Madrid, Spain.

Hepatitis E virus (HEV) is an infectious agent causing hepatitis among humans. Although hepatitis E has been reported from many European countries, its incidence in Europe is largely unknown, and the prevalence of the HEV infection is also unknown for most countries of the region. Antibody to HEV (anti-HEV) was tested on 2,305 serum samples from the general population of the Community of Madrid (Spain) collected in the year 2008 among people aged 2-60 years. Total anti-HEV was tested by enzyme-immunoassay (EIA), and reactive samples were retested separately for anti-HEV IgG and IgM by recombinant immunoblot test (RIBT). Fifty samples (2.17%) displayed reactivity for total anti-HEV after EIA testing, and anti-HEV IgG was confirmed by RIBT in 25 (1.08%). The frequency of RIBT-confirmed anti-HEV ranged from 0.97% among the youngest to 3.61% among the oldest, and displayed a statistically significant trend to increasing with age. The rate of RIBT confirmation was also significantly higher among the individuals aged above 20 years old than among those younger of 21 years. HEV infection would be less frequent in the Community of Madrid than in Catalonia or the United Kingdom, and contact with HEV would be very uncommon among children and adolescents of the region. Confirmation of EIA-reactive samples by RIBT reduced the final numbers of anti-HEV testing as much as 50%, and some findings of this study suggest that such testing protocol would reflect better the real prevalence of anti-HEV in settings of low endemicity than the single testing by EIA.

Imported and autochthonous hepatitis E virus strains in Spain.

Hepatitis E virus (HEV) causes hepatitis E, an acute liver disease displaying diverse epidemiological patterns that correlate with the genetic diversity of the virus. Only a few strains have been characterized to date from cases of hepatitis E in Spain. Using three sets of new, HEV-specific primers, viral genome fragments were amplified from serum samples from 13 patients with acute hepatitis in different regions of Spain. Direct sequencing of these fragments and analysis of sequences lead to identify six genotype 1, six genotype 3, and one genotype 4 viral strains. Genotype 1 sequences were found in the clade with subtype 1a strains, and were amplified from travelers from India and Bangladesh, and from an African immigrant. Genotype 3 sequences were found in the clade with subtype 3f strains, were always amplified from patients who did not travel abroad recently, and were closely related to sequences from swine strains isolated in Spain. Patients infected by these strains lived in different regions and were mainly men aged above 50 years. The single genotype 4 sequence detected was amplified from a traveler returning from Vietnam. Hepatitis E is both an imported and an autochthonous disease in Spain, and closely related HEV genotype 3f strains are responsible for infections acquired locally in different regions of the country within a given time. Studies involving a significant number of human, swine, and environmental viral strains collected prospectively are, however, required in order to confirm a swine origin for autochthonous HEV genotype 3 human infections.

BK virus in liver transplant recipients: a prospective study.

BACKGROUND: BK virus (BKV) is a polyomavirus that is associated with nephropathy and graft loss among kidney transplant recipients. The role of BK virus in nonrenal solid organ transplant recipients has not been clearly established; only anecdotal case reports have been published. METHODS: From August 2005 to September 2007, all liver transplant (OLT) recipients who gave their consent were enrolled in this prospective longitudinal study. BK viral load was measured using real-time quantitative polymerase chain reaction assays of urine and plasma, using samples collected at week 1 and months 1, 3, 6, 9, 12, 15, 18, 21, and 24 posttransplantation. We also collected demographic and clinical data, including serum creatinine and immunosuppressive therapy. RESULTS: The mean age of the 62 patients was 51.4 years including 14 (22.5%) women. Hepatitis C infection was present in 24 patients (38.7%). BK viruria was detected in 14.5% of 290 samples, corresponding to 13 patients (21%). BK viremia was detected in 5.1% of 317 samples, corresponding to 11 patients (18%). Almost all cases of BK viremia (91%) occurred in the first 3 months after OLT. BKV viremia was more common among patients experiencing a rejection episode (10.6 vs 40%, P = .01). We did not observe a relationship between single episodes of BKV replication and renal function: median plasma creatinine 1.1 mg/dL in patients without versus 1.2 mg/dL with BKV viremia. The three patients with persistent viremia displayed renal insufficiency; one of them died due to multiorgan failure of unknown origin. CONCLUSIONS: BKV is frequently detected in OLT recipients (viruria 21% and viremia 18%) early after transplantation. It is more common among patients with rejection episodes. Persistent BKV viremia may be related to renal dysfunction in OLT patients.

Detection of hepatitis G virus from serum and liver of a patient with long-term liver dysfunction after autologous bone marrow transplantation.

Long-term effects after blood or bone marrow transplantation (BMT) are emerging as an important issue, as more patients are included in BMT programmes and as this procedure becomes more successful. Long-term liver dysfunction, mainly due to chronic graft-versus-host disease or hepatitis C virus infection, is a well-known complication. Nevertheless, the diagnosis of liver disease in this patient group is sometimes difficult and, despite adequate studies, it may remain undetected. A novel hepatitis-associated virus, hepatitis G virus (HGV), has recently been identified. The virus belongs to the Flaviviridae family and is known to be parenterally transmitted, although there is no clear evidence to implicate this agent in causing acute or chronic hepatitis. We report a patient who developed mild, but persistent, abnormalities in transaminases for 2 years after an autologous BMT. HGV RNA was detected in both serum and liver. HGV RNA persisted in serum for at least 8 months. No other known hepatitis virus was found. This report provides the first direct evidence of a patient with long-term liver abnormalities after a BMT in whom the only known hepatitis virus isolated was the HGV.

Diagnosis of acute hepatitis E by antibody and molecular testing: a study on 277 suspected cases.

BACKGROUND: Acute hepatitis due to hepatitis E virus (HEV) infection is both indigenous and imported to Europe. Few studies provide information about the role of HEV as an agent for acute hepatitis in Spain. OBJECTIVES: To investigate the frequency of the HEV infection among patients displaying acute hepatitis of unexplained origin in Spain, comparing the performance of two different diagnostic approaches. STUDY DESIGN: Specific IgM antibody and HEV RNA tests were used to study samples from 277 patients with acute hepatitis of unknown aetiology received during a six-year period. Samples were sent by 52 hospitals from almost all regions of Spain. RESULTS: Evidence of acute infection by HEV was obtained for 30 patients in total (10.8%), and 16 cases were unrelated to recent international travel. On samples from 158 patients tested for both anti-HEV IgM and HEV RNA at admission, the yield of IgM antibody testing (11.4%) was higher than the yield of HEV RNA testing (9.5%). CONCLUSIONS: HEV could be responsible in Spain of about 11% of cases of acute hepatitis of unknown origin overall, and of about 8% of cases unrelated to international travel or immigration. India and neighbour countries represent the highest risk for import of epidemic HEV strains into Spain. Both antibody assays and molecular tests are required to optimise the final yield of laboratory diagnosis.

Differential diagnosis of hepatitis E virus, cytomegalovirus and Epstein-Barr virus infection in patients with suspected hepatitis E.

BACKGROUND: The accuracy of the diagnosis of hepatitis E in the clinical setting relies mainly on the performance of assays for hepatitis E virus (HEV)-specific IgM (anti-HEV IgM) testing in serum. OBJECTIVES: Identification of factors influencing the specificity of the results obtained with these assays is an important issue in regard to the accuracy of the diagnosis. STUDY DESIGN: Anti-HEV IgM and HEV RNA were studied in samples from 153 patients with acute hepatitis of unknown aetiology received during a two-year period. Fifteen patients were positive for anti-HEV IgM, and eight of them were also positive for HEV RNA. Investigation of CMV and Epstein-Barr virus (EBV) infection markers among the remaining seven patients, and of HEV infection markers among 18 patients with infectious mononucleosis, was performed. RESULTS: The results obtained showed that acute infection by CMV or EBV may cause false reactivity for anti-HEV IgM, likely because of polyclonal B-cell stimulation. CONCLUSIONS: Since infection by these herpesviruses may produce acute hepatitis, such event can cause diagnostic mistakes and should be investigated in patients positive for anti-HEV IgM and negative for HEV RNA.

GB virus C RNA in serum, liver, and peripheral blood mononuclear cells from patients with chronic hepatitis B, C, and D.

BACKGROUND & AIMS: No conclusive data about GB virus C (GBV-C) tropism are available. We have studied the presence of genomic and antigenomic GBV-C RNA in serum, liver, and peripheral blood cells of 56 patients with chronic hepatitis B, C, or D virus infection. METHODS: Genomic and antigenomic GBV-C RNA were detected by reverse-transcription nested polymerase chain reaction. Specificity was confirmed by sequencing, by chemical modification of the RNA, and by using tagged primers. RESULTS: Genomic GBV-C RNA was found in 10 of 56 (18%) of the sera. In contrast, antigenomic strand was not detected. The sequence of the amplified GBV-C RNA from 3 patients showed a 96% homology among them and from 83% to 88% with previously described isolates. Genomic GBV-C RNA was found in 7 of 7 liver samples of the patients with serum GBV-C RNA. In 6 of these 7 patients (85%), antigenomic strand was found. Genomic RNA was found in 7 of 7 of the peripheral blood cell samples of the same 7 patients. Antigenomic GBV-C RNA was not found in these cells. CONCLUSIONS: These results suggest that GBV-C is a hepatotropic virus that replicates in the human liver. The data do not support a role for GBV-C in chronic liver disease.

In vitro infection of human peripheral blood mononuclear cells by GB virus C/Hepatitis G virus.

GB virus C (GBV-C), also known as hepatitis G virus, is a recently discovered flavivirus-like RNA agent with unclear pathogenic implications. To investigate whether human peripheral blood mononuclear cells (PBMC) are susceptible to in vitro GBV-C infection, we have incubated PBMC from four healthy blood donors with a human GBV-C RNA-positive serum. By means of (i) strand-specific reverse transcription-PCR, cloning, and sequencing; (ii) sucrose ultracentrifugation and RNase sensitivity assays; (iii) fluorescent in situ hybridization; and (iv) Western blot analysis, it has been demonstrated that GBV-C is able to infect in vitro cells and replicate for as long as 30 days under the conditions developed in our cell culture system. The concentration of GBV-C RNA increased during the second and third weeks of culture. The titers of the genomic strand were 10 times higher than the titers of the antigenomic strand. In addition, the same predominant GBV-C sequence was found in all PBMC cultures and in the in vivo-GBV-C-infected PBMC isolated from the donor of the inoculum. GBV-C-specific fluorescent in situ hybridization signals were confined to the cytoplasm of cells at different times during the culture period. Finally, evidence obtained by sucrose ultracentrifugation, RNase sensitivity assays, and Western blot analysis of the culture supernatants suggests that viral particles are released from in vitro-GBV-C-infected PBMC. In conclusion, our study has demonstrated, for the first time, GBV-C replication in human lymphoid cells under experimental in vitro infection conditions.

Phylogenetic analysis of hepatitis GB virus type C/hepatitis G virus in Spanish patients with chronic hepatitis B or C virus infection.

The nucleotide sequence of hepatitis GB virus type C (HGBV-C)/hepatitis G virus (HGV) NS3/helicase and 5'-untranslated regions from 23 Spanish patients were analyzed to assign the HGV isolates one of the proposed HGBV-C/HGV genotypes. The analysis of the evolutionary distance frequency showed that the distances among all sequences in NS3/helicase region were distributed around a single peak of 0.20, suggesting that all included sequences belonged to the same HGBV-C/HGV genotype. By contrast, in the 5'-untranslated region, all the distances corresponding to our sequences and those of the HGBV-C/HGV types 2 and 3 were distributed around a major peak of 0.03. The remaining distances corresponding to the HGBV-C/HGV type 1 sequences were distributed around a minor peak of 0.11. The phylogenetic tree and pairwise comparison of evolutionary distances among the 5'-untranslated region of the infected patients and each HGBV-C/HGV genotype demonstrated that our HGBV-C/HGV isolates belonged to subtype 2a (17/23; 78%) and 2b (5/23; 22%). No relation was found between HGBV-C/HGV subtype and hepatitis B or C virus infection.

Existence of distinct GB virus C/hepatitis G virus variants with different tropism.

To study the existence of GB virus C/hepatitis G virus (GBV-C/HGV) variants with different tropism, we have analyzed the heterogeneity and quasispecies composition of GBV-C/HGV isolated from in vitro-infected peripheral blood mononuclear cells (PBMC) and from sera, livers, and PBMC from two chronically infected patients. For this purpose, the GBV-C/HGV 5' noncoding region (5'NCR) was amplified by reverse transcription-PCR and the amplified products were cloned and sequenced. These analyses showed that the master 5'NCR sequences isolated from the in vitro-infected PBMC and from the PBMC isolated from the patient whose serum was used as the inoculum were identical but different from that of the inoculum. Furthermore, phylogenetic analysis revealed that all PBMC sequences grouped together into a branch which was separate from those of the inoculum. For one of the two chronically infected patients, all the sequences from the PBMC and one from the liver clustered into a single branch while the sequences from the serum and all the other liver sequences grouped together in the other branch. For the other patient, the sequences from the serum and PBMC and three sequences from the liver grouped together into one branch, while the remaining five sequences from the liver were separated in a different cluster. In conclusion, our results support the existence of different GBV-C/HGV variants with different tissue tropism.