A gastric sarcoma from 3000 years ago: paleopathological diagnosis at the field.

OBJECTIVE: Ancient remains tell a lot to those who can solve their mysteries. Mummified remains of individuals have the potential to tell their life stories. Pathological conditions in mummies are identified, commonly, thorough macroscopic inspection and radiological techniques. PATIENTS AND METHODS: In 2017, a hypogeum tomb was excavated close to the courtyard of Djehuty's tomb (TT11) at the archaeological site of the Spanish Djehuty Project in Luxor (Egypt). In Sector 10, a set of at least 10 mummies were recovered. All showed clear signs of plundering and were found scattered at the site. Wrappings and associated goods indicated that the individuals were from the first half of the 20th dynasty (922 to 888 BCE). RESULTS: All the individuals were male and from a high social status. Upon removing the individuals for study, two dried stomachs were found. There were clear macroscopic differences. A field histological analysis was performed which revealed that the stomach that showed no alterations, at first glance, presented a pathological pattern that was compatible with gastric sarcoma. CONCLUSIONS: Malignant diseases are seldom described in Paleopathology; to our knowledge, this is the oldest and most unique case of this type of pathology in mummies worldwide.

Could the IgA isotype provide additional information in systemic sclerosis patients? A retrospective study entailing IgA isotyping in a Mediterranean systemic sclerosis cohort.

OBJECTIVES: Anti-CENP-B (ACA), anti-topoisomerase I (ATA) and anti-RNA polymerase III (RP3) autoantibodies are included in the 2013 SSc-ACR/EULAR classification criteria. The detection of additional autoantibodies is of interest when those are negative. Additionally, we wonder if the IgA isotype might play a role in SSc. The aims of the study were to assess the prevalence of ACA, ATA, RP3, and Ro52 autoantibodies of IgG and IgA isotype and to describe their association with clinical manifestations in a cohort of patients with SSc. METHODS: Samples from 97 patients with SSc fulfilling the 2013 ACR/EULAR classification criteria, and 50 blood donors were included and tested for IgA and IgG isotypes of ACA, ATA, RP3, and Ro52 by FEIA. RESULTS: The prevalence of IgG+IgA isotypes for the same specificity was 62.5%, 82.6%, 80.0%, 36.8%, for ACA, ATA, RP3 and Ro52, respectively. Isolated IgG was present in 35.4%, 13.0%, 20.0% and 42.1% of patients for ACA, ATA, RP3 and Ro52, respectively. Only six patients were isolated IgA for a unique specificity. Clinically, ILD tended to be associated with ATA-IgG and ATA-IgG+IgA, telangiectasias with ACA-IgG+IgA and arthritis with ACA-IgA. Indeed, digital ulcers were more frequent in ATA-IgG patients. CONCLUSIONS: Most of the patients presented ACA, ATA, or RP3 autoantibodies of IgA isotype in addition to IgG. Regarding clinical relevance, Ro52-IgG+IgA and ACA-IgG had a tendency towards sineSSc phenotype, while ACA-IgG+IgA to lcSSc phenotype. Thus, if confirmed, the determination of ACA-IgA could provide a tool to stratify patients according to the cutaneous phenotype.

Detection of M2-Type Anti-Mitochondrial Autoantibodies against Specific Subunits in the Diagnosis of Primary Biliary Cholangitis in Patients with Discordant Results.

BACKGROUND: M2-type anti-mitochondrial autoantibodies are considered the hallmark of primary biliary cholangitis and are directed mainly against the E2 subunits of the 2-oxo acid dehydrogenase complex enzymes (PDC, BCOADC and OGDC). The aim of this study was to determine whether a Dot-blot that includes these E2 subunits separately could confirm the results of methods with non-separated subunits in patients with low positive or discordant results between techniques. METHODS: Sera of 24 patients with low positive or discordant results and of 10 patients with clear positive results by non-separated subunits methods were analyzed by Dot-blot with separated subunits. RESULTS: Autoantibodies against E2 subunits of PDC, BCOADC or OGDC were detected in all patients, except in one case from the low positive or discordant results group, by Dot-blot with separated subunits. CONCLUSIONS: It would be advisable to use methods that include the three E2 subunits, and a Dot-blot with separated subunits could confirm doubtful cases by non-separated assays.

Anti-dsDNA B-Cell ELISpot as a Monitoring and Flare Prediction Tool in SLE Patients.

Anti-dsDNA autoantibodies quantification and complement levels are widely used to monitor disease activity in systemic lupus erythematosus (SLE). However, better biomarkers are still needed. We hypothesised whether the dsDNA antibody-secreting B-cells could be a complementary biomarker in disease activity and prognosis of SLE patients. Fifty-two SLE patients were enrolled and followed for up to 12 months. Additionally, 39 controls were included. An activity cut-off (comparing active and non-active patients according to clinical SLEDAI-2K) was established for SLE-ELISpot, chemiluminescence and Crithidia luciliae indirect immunofluorescence tests (≥11.24, ≥374.1 and ≥1, respectively). Assays performances together with complement status were compared regarding major organ involvement at the inclusion and flare-up risk prediction after follow-up. SLE-ELISpot showed the best performance in identifying active patients. High SLE-ELISpot results were associated with haematological involvement and, after follow-up, with an increased hazard ratio for disease flare-up (3.4) and especially renal flare (6.5). Additionally, the combination of hypocomplementemia and high SLE-ELISpot results increased those risks up to 5.2 and 32.9, respectively. SLE-ELISpot offers complementary information to anti-dsDNA autoantibodies to evaluate the risk of a flare-up in the following year. In some cases, adding SLE-ELISpot to the current follow-up protocol for SLE patients can improve clinicians' personalised care decisions.

Predictive value of the adjusted Global Anti-Phospholipid Syndrome Score on clinical recurrence in APS patients: a longitudinal study.

OBJECTIVE: To assess the effect of the average adjusted global APS score (aGAPSS) over time on recurrence of clinical manifestations in APS patients through a retrospective longitudinal study. MATERIAL AND METHODS: The study included 200 patients with APS. The aGAPSS was calculated for each patient at baseline and on a yearly basis for either up to 6 years (minimum 3 years) or just before the clinical event in patients who experienced clinical recurrence. The mean score per patient was computed. In patients under vitamin K antagonists (VKA) the percentage of time spent within the therapeutic range (TTR) was calculated. Cox regression analysis was performed to determine the cut-off value of the aGAPSS with the strongest association with clinical recurrence. RESULTS: Higher average aGAPSS values were found in patients who experienced clinical recurrence in comparison to patients who did not [8.81 (95% CI 7.53, 10.08) vs 6.38 (95% CI 5.64, 7.12), P = 0.001], patients with thrombotic recurrence compared with patients with obstetric recurrence [9.48 (95% CI 8.14, 10.82) vs 4.25 (95% CI 0.85, 7.65), P = 0.006] and patients with arterial thrombosis compared with patients with venous thrombosis [10.66 (S.D. 5.48) vs 6.63 (S.D. 4.42), P = 0.01]. aGAPSS values >13 points were associated with the highest risk of recurrence in multivariate analysis [HR = 3.25 (95% CI 1.93, 5.45), P < 0.0001]. TTR was not statistically different between patients who had thrombosis recurrence and patients who had not. CONCLUSIONS: Our data support the role of periodic (annual) monitoring of the aGAPSS score in predicting clinical recurrence in patients with APS.

Persistence of antiphospholipid antibodies over time and its association with recurrence of clinical manifestations: A longitudinal study from a single centre.

PURPOSE: To analyze the antiphospholipid antibody (aPL) persistence over time in patients with antiphospholipid syndrome (APS) and its association with clinical recurrence and to identify predictors of aPL persistence over time. PATIENTS AND METHODS: 200 patients with a diagnosis of APS and at least three follow-up aPL determinations were included. Persistent aPL profile was defined as the presence of lupus anticoagulant (LAC) and/or IgG/IgM anticardiolipin (aCL) and/or IgG/IgM anti-ß2 glycoprotein-I (aß2GPI) (> 99th percentile) antibodies in at least 66% of follow-up measurements. Multilevel mixed-effect generalized linear models with logit link were used. RESULTS: 112 (56%) patients maintained persistent aPL profiles over time, while 88 (44%) were transient. Median follow-up time was 172.5 months. Follow-up time did not affect the odds of aPL persistence in multivariate analysis (p = 1.00). Baseline triple aPL positivity [OR 78 (95%CI 16.9-359.7, p < 0.001)] and double aPL positivity [OR = 7.6 (95%CI 3.7-15.7, p < 0.001)] correlated with persistent aPLs over time, while isolated LAC [OR = 0.26 (95% CI 0.08-0.49, p = 0.002)] or isolated IgG/IgM aCL [OR = 0.20 (95% CI 0.11-0.59, p = 0.004)] positivity, were predictors of transient aPL profile. Patients with persistent aPLs had higher rate of clinical recurrence in comparison to patients with transient aPLs [OR = 2.48 (95%CI 1.34-4.58, p = 0.003)]. CONCLUSIONS: More than half of patients with baseline medium-high titer aPL positivity had persistent positive aPLs over time. Patients with persistent aPLs were more prone to present recurrence of clinical manifestations. Multiple aPL positivity increased the odds of a persistent aPL profile over time, while isolated LAC and aCL positivity decreased it.

Persistent Antiphospholipid Antibodies Are Not Associated With Worse Clinical Outcomes in a Prospective Cohort of Hospitalised Patients With SARS-CoV-2 Infection.

Objective: Patients with COVID-19 presented with an elevated prevalence of antiphospholipid antibodies (aPL) but the relationship with thrombosis is controversial. We analysed the persistence of aPL and their association with the clinical outcomes during hospitalisation in a cohort of COVID-19 patients. Patients and Methods: We conducted a prospective study including consecutive hospitalised patients with COVID-19 from Hospital Clínic of Barcelona between March 28th and April 22nd, 2020. Clinical outcomes during hospitalisation were thrombosis, intensive care unit (ICU) admission, and severe ventilatory failure. We determined both criteria and non-criteria aPL. Of note, in those patients with a positive result in the first determination, a second sample separated by at least 12 weeks was drawn to test the persistence of aPL. Results: One hundred and fifty-eight patients (59.5% men) with a mean age of 61.4 ± 14.9 years old were included. Thrombosis was present in 28 (17.7%) patients, severe respiratory failure in 47 (30.5%), and 30 (18.9%) patients were admitted to ICU. Sixteen (28.6%) patients were positive for the criteria aPL at both determinations and only two (3.6%) of them suffered from thrombosis during hospitalisations (both had aCL IgG). However, they presented with low titers of aCL. Of note, aPL were not related to thrombosis, ICU admission or severe respiratory failure. Conclusion: Although aPL were prevalent in our cohort of hospitalised COVID-19 patients and they were persistent in half of tested patients, most determinations were at low titers and they were not related to worse clinical outcomes.

Working Algorithms and Detection Methods of Autoantibodies in Autoimmune Liver Disease: A Nationwide Study.

Autoantibody detection is the cornerstone of autoimmune liver diseases (AILD) diagnosis. Standardisation of working algorithms among autoimmunity laboratories, as well as being aware of the sensitivity and specificity of various commercial techniques in daily practice, are still necessary. The aim of this nationwide study is to report the results of the 2020 Autoimmunity Workshop organised by the Autoimmunity Group of the Spanish Society of Immunology and to provide useful information to clinicians and laboratory specialists to improve the management of autoantibody detection in AILD diagnoses. Serum samples from 17 patients with liver diseases were provided by the organisers of the 2020 Autoimmunity Workshop and were subsequently analysed by the 40 participating laboratories. Each laboratory used different techniques for the detection of autoantibodies in each patients' serum sample, according to their working algorithm. Thus, almost 680 total complete patient reports were obtained, and the number of results from different autoantibody detection techniques was >3000. Up to eight different working algorithms were employed, including indirect immunofluorescence assays (IFA) and antigen-specific techniques (AgST). The IFA of HEp-2 cells was more sensitive than IFA of rat triple tissue for the study of anti-nuclear autoantibodies (ANA) associated with AILD. The IFA of a human neutrophil study for the analysis of anti-neutrophil cytoplasmic autoantibodies was not carried out systemically in all patients, or by all laboratories. AgSTs were the most sensitive methods for the detection of anti-smooth muscle/F-actin, soluble liver antigen, liver cytosol-1, M2-mitochondrial autoantibodies, and ANA associated with primary biliary cholangitis. The main differences in AMA detection were due to patients with autoantibodies against the non-dominant epitope of pyruvate dehydrogenase complex. Given that they are complementary, IFA and AgST should be performed in parallel. If there is high suspicion of AILD, AgST should always be performed.

Congenital kyphosis due to a body agenesis from Ancient Egypt.

In Paleopathology, total lack of a vertebral body is a rare finding, mostly due to infectious diseases or tumors. We report the case of an adult male from the necropolis next to "Temple of the Millions of Years" of Thutmose III dated to the Late Old Kingdom and First Intermediate Period (2345-2055 BCE). He showed a fracture of T12, more than 50%, associated with the complete disappearance of the body of L1 and bilateral transverse process. Infection and tumor involvement were ruled out due to the morphology of the spinal segment. The most likely diagnosis was complete body agenesis. Congenital kyphosis related to vertebral agenesis has been described as a possibility in paleopathology, but it had not been reported until now.

Anti-Phosphatidylserine/Prothrombin Antibodies at Two Points: Correlation With Lupus Anticoagulant and Thrombotic Risk.

Antibodies to phospholipids (aPL) and associated proteins are a hallmark in the diagnosis of anti-phospholipid syndrome (APS). Those included in the classification criteria are the lupus anticoagulant (LA) and the IgG and IgM isotypes of anticardiolipin (aCL) and anti-beta-2 glycoprotein I (ß2GPI) antibodies. Non-classification criteria markers such as autoantibodies that recognize the phosphatidylserine/prothrombin (aPS/PT) complex have been proposed as biomarkers for APS. Studies of aPS/PT antibodies have shown a strong correlation to clinical manifestations and LA. We aimed to study the value and the persistence of aPS/PT IgG and IgM antibodies in a cohort of consecutive patients with clinical suspicion of APS and their utility as thrombotic risk markers. Our study, with 103 patients, demonstrates that persistently positive results for aPS/PT IgG antibodies were significantly associated with APS classification, thrombosis, triple aPL positivity, LA positive result, and the Global APS Score (GAPSS) > than 9 points (p < 0.01, for each condition). On the other hand, no association was seen with pregnancy morbidity (p = 0.56) and SLE (p = 0.07). Persistence of aPS/PT antibodies, defined according to the current laboratory classification criteria, likely improves the diagnosis and clinical assessment of patients with APS.

A new methodology to estimate flat foot in skeletal remains - the example of Mediterranean collections.

Flat feet (pes planus) are considered a postural defect caused by the collapse of the longitudinal arch, producing complete or near-complete contact of the sole of the foot with the ground. Pes planus has been well-studied in clinical literature and paleoanthropology but has not been approached extensively in bioarchaeology. The main difficulty is related to the diagnosis of this pathology based exclusively on bone remains. In this work, we propose a metric and morphological method to discriminate flat foot in dry bones. Thus, we studied 390 pairs of adult feet in a fair state of preservation from archaeological contexts from Spain, Italy, and Oman. Morphological variability, angles, and dimensions of both the normal bones and the bones displaying flat foot characteristics were analyzed. We found a correlation between the presence of flat foot and some morphological and metric features, mainly in the subtalar and Chopart joints. These results are expressed through a combination of morphological and metric variables, which are useful to discriminate between these two groups. No markedly significant differences of flat foot frequencies between the Spanish and Italian series were found across centuries. However, we noticed a notable increase of the prevalence of flat foot in the contemporary collection, possibly due to the consequences of a rise in life expectancy and modern styles of footwear.

The impact of SARS-CoV-2 coronavirus infection in patients with systemic lupus erythematosus from a single center in Catalonia.

OBJECTIVE: To evaluate the incidence and characteristics of SARS-CoV-2 infection among patients with systemic lupus erythematosus (SLE) and to compare it to that described in the general population. METHODS: For 5 weeks, we carried out a cross-sectional study consisting of telephone interviews of SLE patients. We collected epidemiological data, symptoms suggesting COVID-19, results of nasopharyngeal swabs, and ongoing treatments. In those patients who required hospital admission, clinical, radiological, and laboratory features, and outcome were investigated. RESULTS: Four hundred patients with SLE completed the survey. Overall, 4 (1.00%, 95%CI 0.02-1.98) patients were classified as confirmed cases of COVID-19 and 26 (6.51%, 95%CI 4.08-8.94) as possible clinical cases. The incidence of confirmed cases in our series was similar to that of the Catalan population (1.00% versus 0.63%; p = 0.456), whereas the incidence of possible cases was higher in our series (6.51% versus 1.29%; p < 0.005). The only difference between SLE patients with confirmed and possible COVID-19 and those without was the percentage of patients who have had contact with a confirmed or possible case of COVID-19 (26.7% versus 9.2%; p = 0.003) CONCLUSIONS: The incidence of COVID-19 in SLE patients with inactive disease is low and, in our series, all cases with confirmed infection recovered. Key Points • In a cohort of SLE patients with stable and clinical inactive disease, the incidence of COVID-19 is low. • All SLE patients with confirmed SARS-CoV-2 infection recovered.

Hepatopatías autoinmunitarias / No disponible

No disponible

Non-Bacterial Thrombotic Endocarditis: A Presentation of COVID-19.

The SARS-CoV-2 virus is a newly emergent pathogen first identified in Wuhan, China, and responsible for the COVID-19 global pandemic. In this case report we describe a manifestation of non-bacterial thrombotic endocarditis with continuous peripheral embolization in a COVID-19-positive patient. The patient responded well to high-dose LMWH treatment with cessation of the embolic process. LEARNING POINTS: Raising awareness of possible complications of COVID-19.To highlight the importance of the careful consideration of and dosage of anticoagulation in non-bacterial thrombotic endocarditis.

Morphological and biomechanical implications of cuboid facet of the navicular bone in the gait / Implicaciones morfológicas y biomecánicas de la faceta cuboídea del navicular en la marcha

The cuboid facet of the navicular bone is an irregular flat surface, present in non-human primates and some human ancestors. In modern humans, it is not always present and it is described as an "occasional finding". To date, there is not enough data about its incidence in ancient and contemporary populations, nor a biomechanical explanation about its presence or absence. The aim of the study was to evaluate the presence of the cuboid facet in ancient and recent populations, its relationship with the dimensions of the midtarsal bones and its role in the biomechanics of the gait. 354 pairs of naviculars and other tarsal bones from historical and contemporary populations from Catalonia, Spain, have been studied. We used nine measurements applied to the talus, navicular, and cuboid to check its relationship with facet presence. To analyze biomechanical parameters of the facet, X-ray cinematography was used in living patients. The results showed that about 50 % of individuals developed this surface without differences about sex or series. We also observed larger sagittal lengths of the talar facet (LSAGTAL) in navicular bones with cuboid facet. No significant differences were found in the bones contact during any of the phases of the gait. After revising its presence in hominins and non-human primates, and its implication in the bipedalism and modern gait, we suggest that cuboid facet might be related with the size of talar facet and the position of the talonavicular joint. However, other factors such as geographical conditions, genetics and stressful activities probably affect its presence too.

La faceta cuboídea del hueso navicular es una carilla plana e irregular, presente en primates no humanos y en algunos de nuestros ancestros. En humanos modernos, no siempre está presente y es descrita como "un hallazgo ocasional" por la bibliografía. Hasta la fecha, no hay suficientes datos acerca de su incidencia en poblaciones antiguas y contemporáneas, ni una explicación biomecánica sobre su presencia o ausencia. El objetivo de nuestro estudio fue evaluar la frecuencia de la faceta cuboídea en poblaciones recientes y antiguas, su relación con las dimensiones de los huesos tarsales y su rol en la biomecánica de la marcha. Fueron estudiados 354 pares de naviculares y otros huesos del tarso provenientes de colecciones osteológicas de Cataluña, España. Aplicamos nueve medidas aplicadas al talus, navicular y cuboides para corroborar su relación con la presencia de la faceta. Para analizar sus parámetros biomecánicos, se empleó X-ray cinematography en pacientes hospitalarios. Los resultados mostraron que alrededor de un 50 % de los individuos desarrollaron esta carilla, sin diferencias entre sexos o series. Además, observamos que la longitud sagital de la faceta talar (LSAGTAL) es mayor en aquellas muestras con faceta cuboídea. No hay diferencias significativas en el contacto de los huesos en ninguna de las fases de la marcha. Después de revisar su presencia en primates no humanos, su implicancia en el bipedismo y en la marcha moderna, sugerimos que la faceta cuboídea podría estar relacionada con el tamaño de la faceta talar y la posición de la articulación talo-navicular. Sin embargo, otros factores como las condiciones geográficas, genética y stress ocupacional también podrían afectar su presencia.

Syrinx in Spinal Cord in Mummified Individual from West Thebes (Egypt).

We analyzed a total of 36 partial or complete mummies containing neural structures from Sharuna and Qarara (Middle Egypt) and Dra Abu-el Naga, West Thebes (Upper Egypt). Individual TT16 13.3-B06-Ind07 corresponded to a partial mummy from T2 to T11. At distal levels, it showed a structure compatible with the lower spinal cord (SC). Under magnification, the structure presented an absence of meningeal remains and a butterfly-like substructure resembling the anterior and posterior horns of the gray matter of the SC. Meanwhile, the central canal of the spinal cord (syrinx) was considerably enlarged. Field radiograph confirmed a structure compatible with the SC with a syrinx that shows a maximum diameter of 3.2 mm measured by digital caliper. Bearing in mind the normal shrinking mechanism at work in mummification, a pathologic condition such as syringomyelia during the individual's life is a distinct possibility. After a thorough review of the literature, this would be the earliest report of syringomyelia.

Earliest Probable Case of Mueller-Weiss Disease From Ancient Egypt.

Mueller-Weiss disease is an alteration of the tarsal navicular that is primarily due to anomalous ossification of the bone and lateral deviation of the talar head associated with screw-like movement through the axis of the subtalar joint. This syndrome tends to be associated with various degrees of flatfoot and hindfoot valgus combined with subtalar joint varus. Ancient cases of Mueller-Weiss disease have not been described in specialized literature. We present the case of an adult male from the Hellenistic period (Ptolemaic dynasty; fourth to first century BC), the skeleton for which was found inside a sarcophagus in the archaeological site of Sharuna (middle Egypt) with Mueller-Weiss disease. The specimen is, in all likelihood, the earliest case of this type of foot pathology in the archaeological record.

A case of enchondroma from Carolingian necropolis of St. Pere De Terrassa (Spain): An insight into the archaeological record.

Enchondromas occur with an estimated modern incidence rate of 27.7% of benign bone tumors (Hauben and Hogendoorn, 2010), but few are represented in the paleopathological record. The medieval site of St. Pere in Spain has produced a convincing case. The diagnosis was confirmed by X-Ray, CT-scan and µ-CT scan. Therefore UF 755 from St. Pere - a male of more than 60 years old - can be confirmed as a femoral case of enchondroma, supported by evidence, in the paleopathological record.

Oldest epiphyseal osteochondroma in a subadult from Ancient Egypt.

Benign bone tumours are pathologies frequently encountered in archaeological human remains, with the most common being osteoma and osteochondroma. We present the case of a juvenile individual recovered from the Necropolis of Sharuna, Middle Egypt and dated to the end of Old Kingdom and First Intermediate Period of Ancient Egypt (circa 2150 BC), showing an osteochondroma arising from the proximal epiphysis of the right tibia which, in all likelihood, affected the patellar tendon in life. Osteochondromas are usually discovered during childhood and adolescence. These lesions are commonly located at the metaphysis and diaphysis of long bones and directed away from the joint, with the epiphysis being a rare location. To our knowledge, there have been no similar cases published to date from ancient times and we conclude that this is the oldest case of epiphyseal osteochondroma reported.

Oldest Mummified Case of Hallux Valgus from Ancient Egypt.

Hallux valgus is the most common orthopedic problem of the adult foot. The etiology can be congenital, associated with the occurrence of metatarsus primus varus, or acquired, which is closely related to wearing ill-fitting shoes. Hallux valgus occurs almost exclusively in shod societies and, therefore, is a very uncommon finding in archaeological remains. We present a partial first ray of the left foot belonging to a dismembered Egyptian mummy recovered in the necropolis of Sharuna (Middle Egypt) and dated to the end of the Old Kingdom (circa 2100 BC). The mummification process led to a metatarsophalangeal joint in connection by means of soft tissues. The alignment of this joint could be diagnosed as a hallux valgus. Further examination showed a metatarsophalangeal angle of 28°. After a comprehensive literature search and noting that all of the previous cases were described by indirect factors, such as mounting the joint in dry bones, we can state with certainty that the piece we present herein is the oldest case of mummified hallux valgus.