Largest comparison between onset and relapses of acquired thrombotic thrombocytopenic purpura reveals severe neurological involvement and worse analytic parameters at debut.

It has been proposed that the onset of Acquired Thrombotic Thrombocytopenic Purpura (iTTP) is more severe than subsequent relapses; however, existing studies have limitations. We conducted a retrospective observational study to compare analytical and clinical severity of onset and relapse aTTP cases between 2012 and 2023. A total of 370 episodes of aTTP were analyzed, comprising 272 at initial diagnosis and 98 relapses. At onset, analytical parameters indicative of severity (low hemoglobin, low platelet count, and increased LDH) were significantly worse; patients had severe neurological symptoms (p<0.001) and ≥ 3 points in the TMA mortality score (p<0.001). In conclusion, the onset of aTTP is associated with worse analytical parameters and severe neurological involvement.

Movement-driven modelling reveals new patterns in disease transmission networks.

Interspecific interactions are highly relevant in the potential transmission of shared pathogens in multi-host systems. In recent decades, several technologies have been developed to study pathogen transmission, such as proximity loggers, GPS tracking devices and/or camera traps. Despite the diversity of methods aimed at detecting contacts, the analysis of transmission risk is often reduced to contact rates and the probability of transmission given the contact. However, the latter process is continuous over time and unique for each contact, and is influenced by the characteristics of the contact and the pathogen's relationship with both the host and the environment. Our objective was to assess whether a more comprehensive approach, using a movement-based model which assigns a unique transmission risk to each contact by decomposing transmission into contact formation, contact duration and host characteristics, could reveal disease transmission dynamics that are not detected with more traditional approaches. The model was built from GPS-collar data from two management systems in Spain where animal tuberculosis (TB) circulates: a national park with extensively reared endemic cattle, and an area with extensive free-range pigs and cattle farms. In addition, we evaluated the effect of the GPS device fix rate on the performance of the model. Different transmission dynamics were identified between both management systems. Considering the specific conditions under which each contact occurs (i.e. whether the contact is direct or indirect, its duration, the hosts characteristics, the environmental conditions, etc.) resulted in the identification of different transmission dynamics compared to using only contact rates. We found that fix intervals greater than 30 min in the GPS tracking data resulted in missed interactions, and intervals greater than 2 h may be insufficient for epidemiological purposes. Our study shows that neglecting the conditions under which each contact occurs may result in a misidentification of the real role of each species in disease transmission. This study describes a clear and repeatable framework to study pathogen transmission from GPS data and provides further insights to understand how TB is maintained in multi-host systems in Mediterranean environments.

Community-acquired Staphylococcus aureus skin and soft tissue infection risk assessment using hotspot analysis and risk maps: the case of California emergency departments.

BACKGROUND: Community-acquired Staphylococcus aureus (CA-Sa) skin and soft tissue infections (SSTIs) are historically associated with densely populated urban areas experiencing high poverty rates, intravenous drug use, and homelessness. However, the epidemiology of CA-Sa SSTIs in the United States has been poorly understood since the plateau of the Community-acquired Methicillin-resistant Staphylococcus aureus epidemic in 2010. This study examines the spatial variation of CA-Sa SSTIs in a large, geographically heterogeneous population and identifies neighborhood characteristics associated with increased infection risk. METHODS: Using a unique neighborhood boundary, California Medical Service Study Areas, a hotspot analysis, and estimates of neighborhood infection risk ratios were conducted for all CA-Sa SSTIs presented in non-Federal California emergency departments between 2016 and 2019. A Bayesian Poisson regression model evaluated the association between neighborhood-level infection risk and population structure, neighborhood poverty rates, and being a healthcare shortage area. RESULTS: Emergency departments in more rural and mountainous parts of California experienced a higher burden of CA-Sa SSTIs between 2016 and 2019. Neighborhoods with high infection rates were more likely to have a high percentage of adults living below the federal poverty level and be a designated healthcare shortage area. Measures of population structure were not associated with infection risk in California neighborhoods. CONCLUSIONS: Our results highlight a potential change in the epidemiology of CA-Sa SSTIs in California emergency departments. Future studies should investigate the CA-Sa burden in other geographies to identify whether this shift in epidemiology holds across other states and populations. Further, a more thorough evaluation of potential mechanisms for the clustering of infections seen across California neighborhoods is needed.

Vaccination and Nutritional Outcomes of Hemodialysis Patients Infected With SARS-CoV-2.

BACKGROUND: Patients on hemodialysis are particularly vulnerable to COVID-19 and may have a reduced response to vaccination because of a decreased immune response. The nutritional status before or during the infection could also impact on the clinical effectiveness of vaccination. OBJECTIVES: We aim to describe the evolution of clinical and nutritional biomarkers of hemodialysis patients infected with SARS-CoV-2 and to assess their association with vaccination status. METHODS: An observational, analytic, longitudinal, retrospective multicenter study was carried out in 82 patients on hemodialysis with SARS-CoV-2 infection. Nutritional status was assessed using the Geriatric Nutritional Risk Index (GNRI), anthropometry, and biochemical parameters. The association of the vaccine doses with clinical- and nutritional-related variables was also evaluated. RESULTS: The percentage of vaccinated patients was similar to that of nonvaccinated patients. Before infection, most of the patients were malnourished. They presented lower albumin, creatinine, and urea levels than the well-nourished patients. Significant deterioration of nutritional status after infection was evidenced considering GNRI score, dry weight, and body mass index. Albumin and creatinine also decreased significantly after infection, whereas C-reactive protein increased in the acute phase. Significant inverse correlation was found between the variation of post-pre GNRI scores and basal albumin and C-reactive protein at 7 days. In addition, we observed the opposite trend between albumin at 30 days and basal cholesterol. A negative value in the GNRI variation was associated with bilateral pneumonia, need for hospitalization, and nutritional support. Vaccinated patients presented substantially less bilateral pneumonia and hospitalization. No significant effects were observed between vaccine doses and the variation in nutritional status, although a positive correlation was detected with the albumin at 7 days and C-reactive protein before infection and the number of vaccine doses received. DISCUSSION: COVID-19 is associated with affectations in the nutritional status and biomarkers in hemodialysis patients. In this study, vaccines have shown a protective effect against the clinical consequences of COVID. However, they have shown limitations in preventing the deterioration of nutritional status after infection. The results highlight the importance of promoting the vaccination in these patients as well as incorporating nutritional assessment before, during, and after the infection.

Influence of base designs on the manufacturing accuracy of vat-polymerized diagnostic casts using two different technologies.

STATEMENT OF PROBLEM: Diagnostic casts can incorporate different base designs and be manufactured using different vat-polymerization technologies. However, the influence of the interrelation between the base design and the 3D printing technology on the casts' final accuracy remains unclear. PURPOSE: The purpose of this in vitro study was to assess the influence of different base designs of 3D printed casts on the accuracy of 2 vat-polymerization technologies. MATERIAL AND METHODS: A digital maxillary cast was obtained and used to generate 3 different base designs: solid (S group), honeycombed (HC group), and hollow (H group). The HC and H groups were subdivided based on the wall thickness of the cast design, resulting in 2 subgroups with thicknesses of 1 mm (HC1 and H1) and 2 mm (HC2 and H2) (N=100, n=10). Eleven reference cubes were added to each specimen for subsequent measurements. Specimens were manufactured by using 2 vat-polymerization 3D printers: Nextdent 5100 (ND group) and Sonic Mini 4K (SM4K group) and a resin material suitable for both 3D printers (Nextdent Model 2.0). A coordinate measuring machine quantified the linear and 3-dimensional discrepancies between the digital cast and each reference specimen. Trueness was defined as the average absolute dimensional discrepancy between the virtual cast and the specimens produced through additive manufacturing (AM), while precision was delineated as the standard deviation in dimensional discrepancies between the digital cast and the AM specimens. The data were analyzed using the Kruskal-Wallis and Mann-Whitney U pairwise comparison tests (α=.05). RESULTS: For the NextDent group the trueness ranged from 21.83 µm to 28.35 µm, and the precision ranged from 17.82 µm to 37.70 µm. For the Phrozen group, the trueness ranged from 45.15 µm to 64.51 µm, and the precision ranged from 33.51 µm to 48.92 µm. The Kruskal-Wallis test showed significant differences on the x-, y-, and z-axes and in the 3D discrepancy (all P<.001). On the x-axis, the Mann-Whitney U test showed significant differences for the Phrozen group between the H-2 and H-1 groups (P=.001), H-2 and S groups (P<.001), and HC-2 and S groups (P=.012). On the y-axis, significant differences were found in the Phrozen group between the H-2 and H-1 groups (P=.001), the H-2 and S, H-1 and HC-1, and HC-1 and S groups (P<.001), the H-1 and HC-2 groups (P=.007), and the HC-2 and S groups (P=.009). The NextDent group exhibited significant differences, particularly among the HC-1 and H-2 groups (P=.004), H-1 (P=.020), and HC-2 (P=.001) groups; and on the z-axis significant differences were found in the Phrozen group between the H-2 and H-1 and S groups and the HC-2 group and H-1 and S groups (both P<.001). In the NextDent group, significant differences were found between the H-2 and HC-2 (P=.047) and HC-1 (P=.028) groups. For the 3D discrepancy analysis, significant differences were found in the Phrozen group between the H-2 and H-1 and S groups (P<.001), the H-1 and HC-2 groups (P=.001), the S and HC-1 and HC-2 groups (P<.001), and the H-1 and HC-1 groups (P=.002). In the NextDent group, significant differences were observed between the H-2 and HC-1 groups (P=.012). CONCLUSIONS: The accuracy of digital casts depends on the manufacturing trinomial and base design of the casts. The honeycomb and hollow based designs provided the highest accuracy in the NextDent and Phrozen groups respectively for the material polymer tested. All specimens fell in the clinically acceptable range.

Modified Oblique Lobenhoffer (MOL) approach for posterolateral and posteromedial column access in tibial plateau fractures: a detailed cadaveric anatomical study.

BACKGROUND: Tibial plateau fractures involving posteromedial (PM) and posterolateral (PL) columns are complex injuries that require an appropriate approach. The management of the PL column in these cases can be controversial, and limitations using deep posteromedial interval approaches have been referenced. In this paper, a modification of the Lobenhoffer approach, designed to optimize the access to the PL column, is described in detail. The aim of this study was to assess the feasibility of this approach in a cadaveric anatomical study. MATERIALS AND METHODS: In total, five fresh-frozen cadaveric specimens were used for detailed anatomical study surrounding the approach. Relationships with cutaneous and deep neurovascular structures were evaluated. The exposure area of the PL and PM columns using this approach was assessed. RESULTS: The cadaveric study showed safe and adequate exposure. Oblique skin and fascia incision just medial to the posterior midline was safe to protect the medial sural cutaneous nerve and the small saphenous vein. Elevation of the popliteus and tibialis posterior muscles offered safe protection of the anterior tibial artery and popliteal neurovascular bundle during retractor placement. Adequate full proximal exposure of the PM and PL columns, including the posterolateral lateral (PLL) and posterolateral central (PLC) segments, was obtained in all specimens. CONCLUSIONS: The Modified Oblique Lobenhoffer (MOL) approach can be a feasible option to access PL and PM columns in tibial plateau fractures. LEVEL OF EVIDENCE: IV.

Monitoring Temporal Changes in SARS-CoV-2 Spike Antibody Levels and Variant-Specific Risk for Infection, Dominican Republic, March 2021-August 2022.

To assess changes in SARS-CoV-2 spike binding antibody prevalence in the Dominican Republic and implications for immunologic protection against variants of concern, we prospectively enrolled 2,300 patients with undifferentiated febrile illnesses in a study during March 2021-August 2022. We tested serum samples for spike antibodies and tested nasopharyngeal samples for acute SARS-CoV-2 infection using a reverse transcription PCR nucleic acid amplification test. Geometric mean spike antibody titers increased from 6.6 (95% CI 5.1-8.7) binding antibody units (BAU)/mL during March-June 2021 to 1,332 (95% CI 1,055-1,682) BAU/mL during May-August 2022. Multivariable binomial odds ratios for acute infection were 0.55 (95% CI 0.40-0.74), 0.38 (95% CI 0.27-0.55), and 0.27 (95% CI 0.18-0.40) for the second, third, and fourth versus the first anti-spike quartile; findings were similar by viral strain. Combining serologic and virologic screening might enable monitoring of discrete population immunologic markers and their implications for emergent variant transmission.

"Super-Spreaders" and Person-to-Person Transmission of Andes Virus in Argentina.

BACKGROUND: From November 2018 through February 2019, person-to-person transmission of Andes virus (ANDV) hantavirus pulmonary syndrome occurred in Chubut Province, Argentina, and resulted in 34 confirmed infections and 11 deaths. Understanding the genomic, epidemiologic, and clinical characteristics of person-to-person transmission of ANDV is crucial to designing effective interventions. METHODS: Clinical and epidemiologic information was obtained by means of patient report and from public health centers. Serologic testing, contact-tracing, and next-generation sequencing were used to identify ANDV infection as the cause of this outbreak of hantavirus pulmonary syndrome and to reconstruct person-to-person transmission events. RESULTS: After a single introduction of ANDV from a rodent reservoir into the human population, transmission was driven by 3 symptomatic persons who attended crowded social events. After 18 cases were confirmed, public health officials enforced isolation of persons with confirmed cases and self-quarantine of possible contacts; these measures most likely curtailed further spread. The median reproductive number (the number of secondary cases caused by an infected person during the infectious period) was 2.12 before the control measures were enforced and decreased to 0.96 after the measures were implemented. Full genome sequencing of the ANDV strain involved in this outbreak was performed with specimens from 27 patients and showed that the strain that was present (Epuyén/18-19) was similar to the causative strain (Epilink/96) in the first known person-to-person transmission of hantavirus pulmonary syndrome caused by ANDV, which occurred in El Bolsón, Argentina, in 1996. Clinical investigations involving patients with ANDV hantavirus pulmonary syndrome in this outbreak revealed that patients with a high viral load and liver injury were more likely than other patients to spread infection. Disease severity, genomic diversity, age, and time spent in the hospital had no clear association with secondary transmission. CONCLUSIONS: Among patients with ANDV hantavirus pulmonary syndrome, high viral titers in combination with attendance at massive social gatherings or extensive contact among persons were associated with a higher likelihood of transmission. (Funded by the Ministerio de Salud y Desarrollo Social de la Nación Argentina and others.).

Evaluation of the application of sequence data to the identification of outbreaks of disease using anomaly detection methods.

Anomaly detection methods have a great potential to assist the detection of diseases in animal production systems. We used sequence data of Porcine Reproductive and Respiratory Syndrome (PRRS) to define the emergence of new strains at the farm level. We evaluated the performance of 24 anomaly detection methods based on machine learning, regression, time series techniques and control charts to identify outbreaks in time series of new strains and compared the best methods using different time series: PCR positives, PCR requests and laboratory requests. We introduced synthetic outbreaks of different size and calculated the probability of detection of outbreaks (POD), sensitivity (Se), probability of detection of outbreaks in the first week of appearance (POD1w) and background alarm rate (BAR). The use of time series of new strains from sequence data outperformed the other types of data but POD, Se, POD1w were only high when outbreaks were large. The methods based on Long Short-Term Memory (LSTM) and Bayesian approaches presented the best performance. Using anomaly detection methods with sequence data may help to identify the emergency of cases in multiple farms, but more work is required to improve the detection with time series of high variability. Our results suggest a promising application of sequence data for early detection of diseases at a production system level. This may provide a simple way to extract additional value from routine laboratory analysis. Next steps should include validation of this approach in different settings and with different diseases.

Data Augmentation Effects on Highly Imbalanced EEG Datasets for Automatic Detection of Photoparoxysmal Responses.

Photosensitivity is a neurological disorder in which a person's brain produces epileptic discharges, known as Photoparoxysmal Responses (PPRs), when it receives certain visual stimuli. The current standardized diagnosis process used in hospitals consists of submitting the subject to the Intermittent Photic Stimulation process and attempting to trigger these phenomena. The brain activity is measured by an Electroencephalogram (EEG), and the clinical specialists manually look for the PPRs that were provoked during the session. Due to the nature of this disorder, long EEG recordings may contain very few PPR segments, meaning that a highly imbalanced dataset is available. To tackle this problem, this research focused on applying Data Augmentation (DA) to create synthetic PPR segments from the real ones, improving the balance of the dataset and, thus, the global performance of the Machine Learning techniques applied for automatic PPR detection. K-Nearest Neighbors and a One-Hidden-Dense-Layer Neural Network were employed to evaluate the performance of this DA stage. The results showed that DA is able to improve the models, making them more robust and more able to generalize. A comparison with the results obtained from a previous experiment also showed a performance improvement of around 20% for the Accuracy and Specificity measurements without Sensitivity suffering any losses. This project is currently being carried out with subjects at Burgos University Hospital, Spain.