Post-mortem findings in Spanish patients with COVID-19; a special focus on superinfections.

Introduction: Whole-body autopsies may be crucial to understand coronavirus disease 2019 (COVID-19) pathophysiology. We aimed to analyze pathological findings in a large series of full-body autopsies, with a special focus on superinfections. Methods: This was a prospective multicenter study that included 70 COVID-19 autopsies performed between April 2020 and February 2021. Epidemiological, clinical and pathological information was collected using a standardized case report form. Results: Median (IQR) age was 70 (range 63.75-74.25) years and 76% of cases were males. Most patients (90%,) had at least one comorbidity prior to COVID-19 diagnosis, with vascular risk factors being the most frequent. Infectious complications were developed by 65.71% of the patients during their follow-up. Mechanical ventilation was required in most patients (75.71%) and was mainly invasive. In multivariate analyses, length of hospital stay and invasive mechanical ventilation were significantly associated with infections (p = 0.036 and p = 0.013, respectively). Necropsy findings revealed diffuse alveolar damage in the lungs, left ventricular hypertrophy in the heart, liver steatosis and pre-infection arteriosclerosis in the heart and kidneys. Conclusion: Our study confirms the main necropsy histopathological findings attributed to COVID-19 in a large patient series, while underlining the importance of both comorbid conditions and superinfections in the pathology.

Increased Prevalence of Symptomatic Human Intestinal Spirochetosis in MSM with High-Risk Sexual Behavior in a Cohort of 165 Individuals.

Human intestinal spirochetosis (HIS) can cause gastrointestinal symptoms, although asymptomatic infections have been described. Individuals from low-income countries, people living with HIV, and men who have sex with men (MSM) show increased risk. A retrospective review of all patients diagnosed with HIS (n = 165) between January 2013 and October 2020 at a tertiary hospital in Madrid, Spain, was performed to assess risk factors for symptomatic HIS, symptoms, and response to treatment. Most patients were male (n = 156; 94.5%), 86.7% were MSM, and 23.5% practiced chemsex, of whom most were symptomatic (p = 0.039). Most patients (78.4%) reported unprotected oral-anal intercourse. A total of 124 (81.1%) were symptomatic; diarrhea was the most common complaint (68.3%). Multivariable regression showed increased odds of symptoms associated with age under 41 (odds ratio 5.44, 95% CI 1.87-15.88; p = 0.002). Colonoscopy was normal in 153 (92.7%). Furthermore, 66.7% presented previous or concomitant sexually transmitted diseases (STDs). Among the patients, 102 underwent testing for other gastrointestinal pathogens, with positive results in 20 (19.6%). All symptomatic patients without concomitant gastrointestinal infection presenting improvement on follow-up (42 of 53) had received either metronidazole or doxycycline (p = 0.049). HIS should be considered as a cause of chronic diarrhea in MSM with high-risk sexual behavior after other causes have been ruled out; treatment with metronidazole is recommended. Coinfection with other STDs is common.

Isolated central nervous system Whipple disease.

Background: Whipple disease (WD) is an infection caused by Tropheryma whipplei, which might present in three different forms: classical, localized, and isolated in the central nervous system (CNS). Methods: We report the result of a systematic review of the literature on WD unusually presenting with exclusively neurological symptoms, including two previously unpublished cases. A description of two cases with isolated CNS WD was performed, as well as a literature search in Cochrane, Scielo, and PubMed. Results: Two male adult patients presented with exclusively neurological symptomatology. Both magnetic resonance imaging (MRI) showed an intracranial mass suggestive of brain tumor. The histopathological examination was consistent with WD, with no systemic involvement. In the review of the literature, 35 cases of isolated CNS WD were retrieved. The median age at diagnosis was 43.5 (IQR 31.5-51.5). In 13 patients, the MRI showed a brain mass consistent with a brain tumor. The most common finding in the biopsy was the periodic-acid Schiff-stained foamy macrophages. Only five cases presented the pathognomonic sign of oculomasticatory myorhythmia. Thirteen cases had an adverse outcome that resulted in death during follow-up, whereas another 13 improved. The other nine patients remained stable or presented moderate improvement. Conclusion: Isolated CNS WD is a rare disease that should be considered among the differential diagnosis of CNS mass lesions. Brain biopsy is necessary to establish the diagnosis. It is stressed in the literature that an extended antibiotic course is required to prevent relapses and to control the disease.

Compassionate use of tocilizumab in severe SARS-CoV2 pneumonia.

INTRODUCTION: Tocilizumab (TCZ) is an interleukin-6 receptor antagonist, which has been used for the treatment of severe SARS-CoV-2 pneumonia (SSP), which aims to ameliorate the cytokine release syndrome (CRS) induced acute respiratory distress syndrome (ARDS). However, there are no consistent data about who might benefit most from it. METHODS: We administered TCZ on a compassionate-use basis to patients with SSP who were hospitalized (excluding intensive care and intubated cases) and who required oxygen support to have a saturation >93%. The primary endpoint was intubation or death after 24 h of its administration. Patients received at least one dose of 400 mg intravenous TCZ from March 8, 2020 to April 20, 2020. RESULTS: A total of 207 patients were studied and 186 analyzed. The mean age was 65 years and 68% were male patients. A coexisting condition was present in 68% of cases. Prognostic factors of death were older age, higher IL-6, d-dimer and high-sensitivity C-reactive protein (HSCRP), lower total lymphocytes, and severe disease that requires additional oxygen support. The primary endpoint (intubation or death) was significantly worst (37% vs 13%, p < 0·001) in those receiving the drug when the oxygen support was high (FiO2 >0.5%). CONCLUSIONS: TCZ is well tolerated in patients with SSP, but it has a limited effect on the evolution of cases with high oxygen support needs.

Compassionate Use of Tocilizumab in Severe SARS-CoV2 Pneumonia. When late administration is too late.

IntroductionTocilizumab is an interleukin 6 receptor antagonist which has been used for the treatment of severe SARS-CoV-2 pneumonia (SSP), aiming to ameliorate the cytokine release syndrome (CRS) -induced acute respiratory distress syndrome (ARDS). However, there is no data about the best moment for its administration along the course of the disease. MethodsWe provided tocilizumab on a compassionate-use basis to patients with SSP hospitalized (excluding intensive care and intubated cases) who required oxygen support to have a saturation >93%. Primary endpoint was intubation or death after 24 hours of its administration. Patients received at least one dose of 400 mg intravenous tocilizumab during March 8-2020, through April 20-2020. FindingsA total of 207 patients were studied and 186 analysed. The mean age was 65 years and 68% were male. A co-existing condition was present in 68 % of cases. At baseline, 114 (61%) required oxygen support with FiO2 >0.5 % and 72 (39%) [≤]0.5%. Early administration of tocilizumab, when the need of oxygen support was still below FiO2 [≤]0.5%, was significantly more effective than given it in advanced stages (FiO2 >0.5 %), achieving lower rates of intubation or death (13% vs 37% repectively, p<0{middle dot}001). InterpretationThe benefit of tocilizumab in severe SARS-Cov-2 pneumonia is only expected when it is administrated before the need of high oxygen support. FundingNone.

Meningoencefalitis criptocócica. Epidemiología y factores de riesgo de mortalidad en la era pre- y pos-TARGA / Cryptococcal meningoencephalitis. Epidemiology and mortality risk factors in pre- and post-HAART era

Introducción y objetivo: La meningoencefalitis criptocócica (MC), aunque infrecuente, sigue siendo una importante causa de morbimortalidad en pacientes con sida. Material y métodos: Revisión de los casos de MC en un hospital universitario (1990-2014). El diagnóstico se determinó mediante el aislamiento de Cryptococcus neoformans en el LCR. Se analizó la morbimortalidad temprana (< 12 semanas) y tardía (3-18 meses). Resultados: Se analizaron 32 pacientes de los 2.269 diagnósticos de sida (1,41%): 10 entre 1990-1996 y 22 entre 1997-2014. El antígeno criptocócico en el LCR fue positivo en todos los casos, con títulos > 1.024 en 19 pacientes (63%), presentando este grupo unos recuentos de CD4+ menores (40 ± 33 frente a 139 ± 78 cél/μl) y mayor afectación diseminada que el resto. Tras el primer episodio de MC la tasa de recaídas fue del 34%. La mortalidad global fue del 28% (9/32), muy superior en el período pre-TARGA. Conclusiones: La morbimortalidad de la MC viene determinada por padecer una inmunodeficiencia grave, la presencia de enfermedad diseminada, títulos elevados de antígeno en el LCR y el retraso en el inicio del TARGA (AU)

Introduction and objective: Cryptococcal meningoencephalitis (CM) is an uncommon entity, but remains a major cause of morbidity and mortality in patients with AIDS. Material and methods: Review of CM cases in a university hospital. The diagnosis was determined by isolation of Cryptococcus neoformans in cerebrospinal fluid. Morbidity and mortality was assessed at 12 weeks (early mortality) and between 3 and 18 months after diagnosis (late mortality). Results: We analyzed 32 patients from 2,269 AIDS cases (1.41%). 10 patients between 1990-1996 and 22 between 1997-2014. Cryptococcal antigen in CSF was positive in all cases, with titers > 1,024 in 19 patients (63%); this group had lower CD4+ counts (40 ± 33 vs. 139 ± 78 cel/μL) and greater disseminated involvement. After a first CM episode the relapse rate was 34%. Global mortality rate was 28% (9/32), much higher in the pre-HAART era. Conclusions: CM morbidity and mortality is related to severe immunodeficiency, disseminated disease, high titers of antigen in CSF and delayed initiation of HAART (AU)

[Cryptococcal meningoencephalitis. Epidemiology and mortality risk factors in pre- and post-HAART era]. / Meningoencefalitis criptocócica. Epidemiología y factores de riesgo de mortalidad en la era pre- y pos-TARGA.

INTRODUCTION AND OBJECTIVE: Cryptococcal meningoencephalitis (CM) is an uncommon entity, but remains a major cause of morbidity and mortality in patients with AIDS. MATERIAL AND METHODS: Review of CM cases in a university hospital. The diagnosis was determined by isolation of Cryptococcus neoformans in cerebrospinal fluid. Morbidity and mortality was assessed at 12 weeks (early mortality) and between 3 and 18 months after diagnosis (late mortality). RESULTS: We analyzed 32 patients from 2,269 AIDS cases (1.41%). 10 patients between 1990-1996 and 22 between 1997-2014. Cryptococcal antigen in CSF was positive in all cases, with titers>1,024 in 19 patients (63%); this group had lower CD4+ counts (40 ± 33 vs. 139 ± 78 cel/µL) and greater disseminated involvement. After a first CM episode the relapse rate was 34%. Global mortality rate was 28% (9/32), much higher in the pre-HAART era. CONCLUSIONS: CM morbidity and mortality is related to severe immunodeficiency, disseminated disease, high titers of antigen in CSF and delayed initiation of HAART.

Trypanosoma cruzi strains cause different myocarditis patterns in infected mice.

AIMS: Chagas disease pathology is dependent on the infecting Trypanosoma cruzi strain. However, the relationship between the extent and type of myocarditis caused by different T. cruzi strains in the acute and chronic phases of infection has not been studied in detail. To address this, we infected mice with three genetically distant T. cruzi strains as well as infected in vitro different cell types. METHODS AND RESULTS: Parasitemia was detected in mice infected with the Y and VFRA strains, but not with the Sc43 strain; however, only the Y strain was lethal. When infected with VFRA, mice showed higher inflammation and parasitism in the heart than with Sc43 strain. Y and VFRA caused homogeneous pancarditis with inflammatory infiltrates along the epicardium, whereas Sc43 caused inflammation preferentially in the auricles in association with intracellular parasite localization. We observed intramyocardic perivasculitis in mice infected with the VFRA and Y strains, but not with Sc43, during the acute phase, which suggests that endothelial cells may be involved in heart colonization by these more virulent strains. In in vitro infection assays, the Y strain had the highest parasite-cell ratio in epithelial, macrophage and endothelial cell lines, but Y and VFRA strains were higher than Sc43 in cardiomyocytes. CONCLUSIONS: This study supports parasite variability as a cause for the diverse cardiac outcomes observed in Chagas disease, and suggests that endothelial cells could be involved in heart infection during the acute phase.

Gastritis erosiva por citomegalovirus en un lactante sano: puesta al día a propósito de un caso / Cytomegalovirus erosive ga stritis in a healthy infant: update about a case

El citomegalovirus es un virus ADN de la familia Herpesviridae que puede afectar al tubo digestivo. Dentro de éste, las dianas de afectación suelen ser el colon, el esófago y el estómago. Se ha descrito ampliamente su asociación con el síndrome de Ménétrier (hiperplasia foveolar con pérdida de proteínas), si bien también puede producir cuadros de gastritis erosiva. En el presente artículo se describe un caso de gastritis erosiva en una lactante sana de 4 meses de edad, que se inició en forma de hemorragia digestiva alta. A partir de este caso, se lleva a cabo una puesta al día de este subgrupo de infecciones por citomegalovirus(AU)

Cytomegalovirus is a DNA Herpesviridae family which can affect the digestive tract. From the standpoint of the stomach, has been widely described his association with Ménétrier syndrome(foveolar hyperplasia with protein-losing) but can also produce erosive gastritis. This article describes a case of erosive gastritis in a healthy 4 months infant which debuted as upper gastrointestinal bleeding. In addition we perform an update of this subgroup of cytomegalovirus infections(AU)

Merkel cell carcinoma: what do we know about it and what should we do?

Merkel cell carcinoma (MCC) is a rare primary cutaneous carcinoma of the skin that is highly aggressive, and has a high risk of locoregional and distant spread, a mortality rate considerably higher than that of cutaneous melanoma and poor survival. Its incidence has increased during the past twenty years. The studies published since 2008 have introduced changes in the understanding of its epidemiology and pathogenesis, and consequently the therapeutic approach. Despite this, there is still controversy surrounding its optimal management, which requires clarification. This is the purpose of this review (AU)

Merkel cell carcinoma: what do we know about it and what should we do?

Merkel cell carcinoma (MCC) is a rare primary cutaneous carcinoma of the skin that is highly aggressive, and has a high risk of locoregional and distant spread, a mortality rate considerably higher than that of cutaneous melanoma and poor survival. Its incidence has increased during the past twenty years. The studies published since 2008 have introduced changes in the understanding of its epidemiology and pathogenesis, and consequently the therapeutic approach. Despite this, there is still controversy surrounding its optimal management, which requires clarification. This is the purpose of this review.

Paragonimiasis pulmonar / Pulmonary Paragonimiasis

La paragonimiasis es una zoonosis de transmisión alimentaria causada por un trematodo del género Paragonimus1,2. Se trata de infestación excepcional en España, pero la afluencia de personas originarias de áreas endémicas debe hacernos tener presente esta entidad en el diagnóstico diferencial de nuestros pacientes2,5.Presentamos el caso de un paciente natural de Ecuador y residente en España desde hace 7 años con tuberculosis pulmonar activa a su llegada a España y posterior diagnóstico de paragonimiasis pulmonar a raíz de hemoptisis persistente. El diagnóstico se estableció por muestra quirúrgica pulmonar, objetivando granulomas, englobando los huevos del parásito, así como la visualización macroscópica del trematodo dentro de una cavidad. El tratamiento antituberculoso inicialmente y con prazicuantel en la actualidad controló ambas entidades(AU)

Paragonimiasis is a food-borne zoonosis caused by a trematode of the genus Paragonimus1,2. Infestation is rare in Spain, but the influx of people from endemic areas should make us keep this condition in the differential diagnosis of our patients2,5.We report the case a patient from Ecuador and resident in Spain for 7years with active pulmonary tuberculosis on arrival in Spain and later diagnosed with of pulmonary paragonimiasis due to persistent haemoptysis. The diagnosis was established by surgical lung specimen showing granulomas containing parasite eggs and the macroscopic view of the fluke within a lung cavity. Initial tuberculosis treatment and current treatment with praziquantel controlled both conditions(AU)

[Pulmonary paragonimiasis]. / Paragonimiasis pulmonar.

Paragonimiasis is a food-borne zoonosis caused by a trematode of the genus Paragonimus(1,2). Infestation is rare in Spain, but the influx of people from endemic areas should make us keep this condition in the differential diagnosis of our patients(2,5). We report the case a patient from Ecuador and resident in Spain for 7 years with active pulmonary tuberculosis on arrival in Spain and later diagnosed with of pulmonary paragonimiasis due to persistent haemoptysis. The diagnosis was established by surgical lung specimen showing granulomas containing parasite eggs and the macroscopic view of the fluke within a lung cavity. Initial tuberculosis treatment and current treatment with praziquantel controlled both conditions.

Pericarditis tuberculosa: una entidad infrecuente de una enfermedad frecuente / Tuberculous pericarditis: an unusual presentation of a common disease

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[Bellini's duct carcinoma]. / Carcinoma de los conductos de Bellini.

Two new cases of uncommon Bellini's duct carcinoma are described. The existing literature is reviewed, discussing the clinical manifestations, diagnosis, treatment and embryological aspects, which differentiate from clear cell carcinoma.

Carcinoma de los conductos de Bellini / Bellini's duct carcinoma

Se describen dos nuevos casos del carcinoma de conductos de Bellini, neoplasia renal muy poco frecuente, y se revisa la literatura existente. Comentamos los aspectos clínicos, diagnósticos, terapéuticos y embriológicos que lo diferencian del carcinoma de células claras (AU)