Autoantibodies Neutralizing GM-CSF in HIV-Negative Colombian Patients Infected with Cryptococcus gattii and C. neoformans.

BACKGROUND: Cryptococcosis is a life-threatening disease caused by Cryptococcus neoformans or C. gattii. Neutralizing autoantibodies (auto-Abs) against granulocyte-macrophage colony-stimulating factor (GM-CSF) in otherwise healthy adults with cryptococcal meningitis have been described since 2013. We searched for neutralizing auto-Abs in sera collected from Colombian patients with non-HIV-associated cryptococcosis in a retrospective national cohort from 1997 to 2016. METHODS: We reviewed clinical and laboratory records and assessed the presence of neutralizing auto-Abs against GM-CSF in 30 HIV negative adults with cryptococcosis (13 caused by C. gattii and 17 caused by C. neoformans). RESULTS: We detected neutralizing auto-Abs against GM-CSF in the sera of 10 out of 13 (77%) patients infected with C. gattii and one out of 17 (6%) patients infected with C. neoformans. CONCLUSIONS: We report eleven Colombian patients diagnosed with cryptococcosis who had auto-Abs that neutralize GM-CSF. Among these patients, ten were infected with C. gattii and only one with C. neoformans.

Anti-GM-CSF Neutralizing Autoantibodies in Colombian Patients with Disseminated Cryptococcosis.

BACKGROUND: Cryptococcosis is a potentially life-threatening fungal disease caused by encapsulated yeasts of the genus Cryptococcus, mostly C. neoformans or C. gattii. Cryptococcal meningitis is the most frequent clinical manifestation in humans. Neutralizing autoantibodies (auto-Abs) against granulocyte-macrophage colony-stimulating factor (GM-CSF) have recently been discovered in otherwise healthy adult patients with cryptococcal meningitis, mostly caused by C. gattii. We hypothesized that three Colombian patients with cryptococcal meningitis caused by C. neoformans in two of them would carry high plasma levels of neutralizing auto-Abs against GM-CSF. METHODS: We reviewed medical and laboratory records, performed immunological evaluations, and tested for anti-cytokine auto-Abs three previously healthy HIV-negative adults with disseminated cryptococcosis. RESULTS: Peripheral blood leukocyte subset levels and serum immunoglobulin concentrations were within the normal ranges. We detected high levels of neutralizing auto-Abs against GM-CSF in the plasma of all three patients. CONCLUSIONS: We report three Colombian patients with disseminated cryptococcosis associated with neutralizing auto-Abs against GM-CSF. Further studies should evaluate the genetic contribution to anti-GM-CSF autoantibody production and the role of the GM-CSF signaling pathway in the immune response to Cryptococcus spp.

A factorial experiment grounded in the multiphase optimization strategy to promote viral suppression among people who inject drugs on the Texas-Mexico border: a study protocol.

BACKGROUND: People who inject drugs living with HIV (PWIDLH) suffer the lowest rates of HIV viral suppression due to episodic injection drug use and poor mental health coupled with poor retention in HIV care. Approximately 44% of PWIDLH along the US-Mexico border are retained in care and only 24% are virally suppressed. This underserved region faces a potential explosion of transmission of HIV due to highly prevalent injection drug use. This protocol describes an optimization trial to promote sustained viral suppression among Spanish-speaking Latinx PWIDLH. METHODS: The multiphase optimization strategy (MOST) is an engineering-inspired framework for designing and building optimized interventions and guides this intervention. The primary aim is to conduct a 24 factorial experiment in which participants are randomized to one of 16 intervention conditions, with each condition comprising a different combination of four behavioral intervention components. The components are peer support for methadone uptake and persistence; behavioral activation therapy for depression; Life-Steps medication adherence counseling; and patient navigation for HIV care. Participants will complete a baseline survey, undergo intervention, and then return for 3-,6-,9-, and 12-month follow-up assessments. The primary outcome is sustained viral suppression, defined as viral loads of < 40 copies per mL at 6-,9-, and 12-month follow-up assessments. Results will yield effect sizes for each component and each additive and interactive combination of components. The research team and partners will make decisions about what constitutes the optimized multi-component intervention by judging the observed effect sizes, interactions, and statistical significance against real-world implementation constraints. The secondary aims are to test mediators and moderators of the component-to-outcome relationship at the 6-month follow-up assessment. DISCUSSION: We are testing well-studied and available intervention components to support PWIDLH to reduce drug use and improve their mental health and engagement in HIV care. The intervention design will allow for a better understanding of how these components work in combination and can be optimized for the setting. TRIAL REGISTRATION: This project was registered at clinicaltrials.gov (NCT05377463) on May 17th, 2022.

Replaced right hepatic artery arising from the distal renal artery, a new variation.

PURPOSE: Arterial irrigation of the liver is highly variable and widely studied due to its importance in the correct planification of the surgical or endovascular treatment of the hepatobilary area. Various classifications have been published of the common and uncommon anatomic variations of the hepatic arterial distribution. While the classic anatomic pattern of the proper hepatic artery-when it originates from the celiac trunk dividing into left and right branches-represents 50-83% of the described patterns, there are numerous uncommon distributions based on the presence of replaced or accessory hepatic arteries. In this article, we present a case of a replaced right hepatic artery originating from the right distal renal artery. METHODS: Contrast enhanced computed tomography (CECT) examination was performed on a 67 years-old male patient with compensated alcoholic cirrhosis as part of the disease monitoring. RESULTS: The replaced right hepatic artery of the patient arises from the right distal renal artery and-after its cranial course-enters the porta hepatis posterior to the main portal vein. After giving off the cystic artery, it irrigates the right hepatic lobe. The left hepatic artery does not show any variation. CONCLUSION: We present CT angiography images of an extremely rare anatomic variation of the hepatic arterial irrigation in a cirrhotic patient.

Spirosoma endbachense sp. nov., isolated from a natural salt meadow.

A Gram-stain-negative bacterium, designated I-24T, was isolated from soil of a natural salt meadow. Strain I-24T was aerobic, non-motile, rod-shaped, catalase-positive, oxidase-positive and grew optimally at pH 7 and 25 °C. Comparative 16S rRNA gene analysis indicated that strain I-24T has closest similarities to Spirosoma agri KCTC 52727T (95.9 %) and Spirosoma terrae KCTC 52035T (95.5 %). Strain I-24T contained summed feature 3 (C16 : 1 ω7c/C16 : 1 ω6c) and C16 : 1 ω5c as the major fatty acids, the predominant respiratory quinone was menaquinone MK-7, and the major polar lipids were phosphatidylethanolamine as well as an unidentified phosphoaminolipid. The draft genome of strain I-24T consists of 10 326 072 base pairs with 9153 predicted coding sequences and a G+C content of 47.7 mol%. Clear distinctions between strain I-24T and S. agri KCTC 52727T or S. terrae KCTC 52035T were shown in the pairwise average nucleotide identity results with values of 76.71 and 74.01 %, respectively. Moreover, the digital DNA-DNA relatedness values to these strains were 20.8 and 19.0 %. Based on its phenotypic, genotypic and chemotaxonomic characteristics, strain I-24T represents a novel species of the genus Spirosoma, for which the name Spirosoma endbachense sp. nov. is proposed. The type strain is I-24T (DSM 111055T=KCTC 72613T).

Autoantibodies neutralizing GM-CSF in HIV-negative Colombian patients infected with Cryptococcus gattii and C. neoformans.

Background: Cryptococcosis is a life-threatening disease caused by Cryptococcus neoformans or C. gattii. Autoantibodies (auto-Abs) neutralizing granulocyte-macrophage colony-stimulating factor (GM-CSF) in otherwise healthy adults with cryptococcal meningitis have been described since 2013. We searched for neutralizing auto-Abs in sera from Colombian patients with non-HIV related cryptococcosis in a retrospective national cohort collected from 1997 to 2016. Methods: We reviewed clinical and laboratory records and assessed the presence of neutralizing auto-Abs in 30 HIV (-) adults presenting cryptococcosis (13 by C. gattii, and 17 by C. neoformans). Results: We detected auto-Abs neutralizing GM-CSF in the plasma of 9 out of 13 (69%) patients infected with C. gattii and 1 out of 17 (6%) patients with C. neoformans. Conclusions: We report ten Colombian patients with cryptococcosis due to auto-Abs neutralizing GM-CSF. Nine of the ten patients were infected with C. gattii, and only one with C. neoformans.

MRI Using Gadoxetic Acid in the Work-Up of Liver Nodules Not Conclusively Benign in Budd-Chiari Syndrome: A Prospective Long-Term Follow-Up.

Introduction: The incidence of hepatocellular carcinoma (HCC) in Budd-Chiari syndrome (BCS) is unknown and there is no validated diagnostic work-up to define the liver nodules with arterial phase hyperenhancement (APHE), suggesting malignancy. This prospective study evaluates HCC incidence in a Western cohort of patients with BCS and assesses the performance of MRI with hepatobiliary contrast (HB-MRI) for nodule characterization. Methods: Patients with BCS followed in our hospital were prospectively evaluated by MRI with extracellular contrast (EC-MRI). Nodules with APHE categorized as non-conclusively benign by 2 radiologists were studied by HB-MRI and reviewed by 2 radiologists blinded to the EC-MRI results. A new EC-MRI 1 year later and clinical, analytical, and sonographic follow-up every 6 months for a median of 10 years was performed. Results: A total of 55 non-conclusively benign nodules with APHE were detected at EC-MRI in 41 patients. While 32 of them were suggestive of HCC by EC-MRI, all the 55 nodules showed increased uptake of hepatobiliary contrast. An unequivocal central scar was seen in 12/55 nodules at HB-MRI regardless of it was not detected on the EC-MRI. None of the nodules was hypointense in the hepatobiliary phase (HBP). HCC was not detected during a median of 10 years of follow-up. Conclusions: Detection of nodules with APHE is frequent in patients with BCS, but HCC is rare in Western patients with BCS. While EC-MRI may detect nodules suggesting malignancy, the identification of contrast uptake in the HBP at HB-MRI may help categorize them as benign.

Liver Hydatid Cyst Rupture with Respiratory Distress During COVID-19 Pandemic.

We present a case of a young male patient who was brought to the emergency room with abdominal pain, fever, dyspnea and hypoxemia, and was initially oriented as an acute COVID-19 pneumonia. A thoracoabdominal computed tomography (CT) was performed to rule out pneumonia and the abdominal extension of the study revealed a hepatic hydatid cyst with rupture into the abdominal cavity with respiratory distress secondary to an anaphylactic reaction that, if left untreated, may lead to a fatal outcome. An urgent laparotomy was performed with cyst resection. The follow-up and complications are briefly described.

Second Adjuvant Radioiodine Therapy after Reoperation for Locoregionally Persistent or Recurrent Papillary Thyroid Carcinoma.

Introduction Differentiated thyroid carcinoma (DTC) has increased incidence. Intermediate- and high-risk patients have lymph node relapse rate ranging from 10 to 50%, and receive multiple reinterventions, increasing the morbidity of the disease. Currently, there are no established guidelines for the use of second radioactive iodine (RAI) therapy after the reintervention for local recurrence. Materials and Methods This is a retrospective review of the medical records of 1,299 patients treated from January 2016 to July 2019 with DTC. We included 48 patients who received total thyroidectomy, RAI remnant ablation, surgery to remove the locally recurrent/persistent papillary thyroid carcinoma (PTC), and received a second RAI therapy. Results There were no significant differences between thyroglobulin (Tg) levels before reoperation (Tg0), Tg levels postoperatively (Tg1), and Tg levels after 6 months of second adjuvant RAI therapy (Tg2). However, we evidenced a 69.79% drop in first Tg levels (Tg0: 24.7 vs. Tg1: 7.56, p =0.851) and 44.4% decrease in second Tg levels (Tg1: 7.56 vs. Tg2: 4.20, p =0.544). Also, 77.1% of the patients did not have another documented recurrence. The median relapse-free time was 10.9 months (range: 1.3-58.2 months). Conclusion The results of the study cannot assess that a second RAI treatment after reoperation for locoregionally persistent or recurrent disease have a significant impact on treatment outcomes in intermediate- or high-risk patients with PTC. However, the 77.1% of patients have not presented a second documented recurrence and the median values of Tg and TgAb levels showed a substantial decrease after surgery and second RAI treatment.

68Ga-DOTANOC PET/CT With Lung Involvement in the Era of COVID-19 Pandemic.

ABSTRACT: Patient was a 55-year-old man with history of pancreas neuroendocrine tumor grade 2, Ki-67 index 10%. He was treated with surgical resection. 68Ga-DOTANOC PET/CT was performed as part of follow-up of known disease. The images showed opacities in both lungs' parenchyma with moderate uptake of radiotracer and mediastinal lymph nodes with high uptake suggestive of infection. Two weeks before a high-resolution CT was performed, these findings in the lungs were not present. The patient was asymptomatic and was referred to the emergency department for reverse transcriptase-polymerase chain reaction COVID-19 test, and the result was positive.

The role of contrast enhanced ultrasound in the differential diagnosis of segmental testicular infarction.

A 43-year-old male presented to the emergency department with acute left testicular pain. Physical exam showed a tender left testicle and epididymis with mild swelling. Doppler and contrast enhanced ultrasound revealed a heterogeneous, avascular lesion with hyper vascularized surrounding. Follow-up contrast enhanced ultrasound performed a few days later showed persistence of the sparsely vascularized lesion with more hypoechoic echo structure. Despite the tumor markers being negative, a necrotic tumor could not be ruled out and a left orchiectomy was performed. Pathology report described an extensive segmental testicular infarction with no evidence of malignant tissue. We present the ultrasound and pathology findings, differential diagnostic pearls and clinical perspective of segmental testicular infarction.

What is the role of ultrasonography in the early diagnosis of scaphoid fractures?

Scaphoid fractures are the most prevalent type of carpal bone fractures. High-spatial-resolution sonography detects direct signs of scaphoid fractures such as scaphoid cortical disruption; nevertheless, indirect signs such as radiocarpal effusion and scapho-trapezium-trapezoid effusion can also be visible. The diagnosis is performed when both direct and indirect signs of scaphoid fracture are presented. The presence of indirect signs alone is not enough to complete the diagnosis, for which more advanced imaging modalities are usually required. Here, we review the anatomy of the scaphoid, the clinical manifestations of scaphoid fractures, as well as ultrasonographic findings and differential diagnosis.

X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19.

Autosomal inborn errors of type I IFN immunity and autoantibodies against these cytokines underlie at least 10% of critical COVID-19 pneumonia cases. We report very rare, biochemically deleterious X-linked TLR7 variants in 16 unrelated male individuals aged 7 to 71 years (mean: 36.7 years) from a cohort of 1,202 male patients aged 0.5 to 99 years (mean: 52.9 years) with unexplained critical COVID-19 pneumonia. None of the 331 asymptomatically or mildly infected male individuals aged 1.3 to 102 years (mean: 38.7 years) tested carry such TLR7 variants (p = 3.5 × 10-5). The phenotypes of five hemizygous relatives of index cases infected with SARS-CoV-2 include asymptomatic or mild infection (n=2, 5 and 38 years), or moderate (n=1, 5 years), severe (n=1, 27 years), or critical (n=1, 29 years) pneumonia. Two boys (aged 7 and 12 years) from a cohort of 262 male patients with severe COVID-19 pneumonia (mean: 51.0 years) are hemizygous for a deleterious TLR7 variant. The cumulative allele frequency for deleterious TLR7 variants in the male general population is < 6.5x10-4 We also show that blood B cell lines and myeloid cell subsets from the patients do not respond to TLR7 stimulation, a phenotype rescued by wild-type TLR7 The patients' blood plasmacytoid dendritic cells (pDCs) produce low levels of type I IFNs in response to SARS-CoV-2. Overall, X-linked recessive TLR7 deficiency is a highly penetrant genetic etiology of critical COVID-19 pneumonia, in about 1.8% of male patients below the age of 60 years. Human TLR7 and pDCs are essential for protective type I IFN immunity against SARS-CoV-2 in the respiratory tract.

Use of intensive care, mechanical ventilation, both, or neither by patients with acute lung injury.

OBJECTIVE: Reports of acute lung injury and acute respiratory distress syndrome have generally been restricted to mechanically ventilated intensive care unit patients, creating an incomplete picture of the epidemiologies of the syndromes. We sought to determine the incidence and outcomes of acute lung injury and acute respiratory distress syndromes throughout an entire hospital population. DESIGN: Retrospective cohort study. SETTING: A Department of Veterans Affairs medical center. PATIENTS: All patients satisfying criteria for acute lung injury or acute respiratory distress syndrome during a 2-yr period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 11,465 acute medical and surgical admissions during the study period; 156 patients had acute lung injury or acute respiratory distress syndrome. Only 74 (47%) were invasively ventilated in an intensive care unit for acute lung injury. Another 15 (10%) patients were ventilated for other reasons, 41 (26%) were admitted to an intensive care unit at approximately the time of acute lung injury onset but were not invasively ventilated, and 26 (17%) were managed with neither invasive ventilation nor admission to an intensive care unit. Four-week mortality differed by group (p = .023), ranging from 22% among those managed in an intensive care unit without invasive ventilation to 50% among those ventilated for acute lung injury or acute respiratory distress syndrome. By 2 yrs, differences in survival between groups were no longer significant. Notably, only 53 (34%) patients would have been eligible for widely cited acute lung injury intervention trials. Ten patients had a second episode of acute lung injury during the study period, equating to a 16%-per-year risk of recurrence. CONCLUSIONS: Acute lung injury and acute respiratory distress syndrome studies restricted to patients mechanically ventilated in intensive care units substantially underestimate the incidence of the syndromes. Nonventilated patients and those cared for outside of intensive care units may still be at substantial risk for death. Further characterization of previously overlooked acute lung injury and acute respiratory distress syndrome patients may suggest new therapeutic opportunities.

68Ga-PSMA PET/CT With Incidental Finding of COVID-19 in an Asymptomatic Patient.

A 70-year-old man with prostate adenocarcinoma was diagnosed by transrectal biopsy, with Gleason of 4 + 5 and initial PSA of 225 ng/mL since March 2020. Ga-PSMA PET/CT was performed as part of initial staging. The images showed an enlarged prostate with focal PSMA uptake in both lobes. Retroperitoneal and pelvic lymph nodes with moderate uptake of PSMA were shown. Another finding was a moderate PSMA uptake in the both lung parenchymas associated with opacities in CT. The patient denied any symptoms of coronavirus disease and was referred to the emergency department for RT-PCR COVID-19, and the result was positive.

Incidental findings of COVID-19 in F18-FDG PET/CT from asymptomatic patients with cancer in two healthcare institutions in Bogotá, Colombia / [Hallazgos incidentales de COVID-19 en tomografías PET/CT 18F-FDG de pacientes asintomáticos con cáncer en dos instituciones de salud de Bogotá, Colombia].

COVID-19 is the viral infection caused by SARS-CoV-2 declared by the World Health Organization (WHO) as a pandemic. Patients with cancer have a higher risk to acquire the infection and worse prognosis as they have to attend more medical visits in healthcare institutions, receive medical and surgical treatments, and be subjected to diagnostic studies such as PET/CT in nuclear medicine services where the infection may be an incidental finding. We present here F18-FDG PET/CT (Positron Emission Tomography and Computed Tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose), images with findings of COVID-19 from patients with different oncological conditions but no respiratory symptoms.

La COVID-19 es la infección viral causada por el SARS-CoV-2 y declarada por la Organización Mundial de la Salud (OMS) como pandemia. Los pacientes con cáncer tienen un mayor riesgo de adquirir la infección y un peor pronóstico, ya que deben asistir a visitas médicas en diferentes centros hospitalarios, reciben tratamientos médicos y quirúrgicos y deben someterse a estudios diagnósticos como la PET/CT en servicios de medicina nuclear, lo que es ocasión para el hallazgo incidental de la infección. Se presentan las imágenes de tomografías computarizadas por emisión de positrones con 18-fluorodesoxiglucosa (F18) (Positron Emission Tomography and Computed Tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose, PET/CT F18-FDG) en las que se evidenció la COVID-19 en pacientes con diversas enfermedades oncológicas, pero sin sintomatología respiratoria.

Rectal Neuroendocrine Tumor With Inferior Vena Cava Tumor Thrombosis Diagnosed With 68Ga-DOTANOC PET/CT.

A 69-year-old man with a history of back pain, urinary obstruction, and deep vein thrombosis of both lower extremities 4 years earlier was diagnosed with rectal neuroendocrine tumor, grade 2, Ki-67 index 3%. Ga-DOTANOC PET/CT images showed a left pelvic mass extended to the lumen of the inferior vena cava with a high affinity for somatostatin receptor. A tubular focus of radiotracer accumulation after the course of inferior vena cava with filling defect was suggestive of tumor thrombus.

Draft Genome Sequences of Spirosoma agri KCTC 52727 and Spirosoma terrae KCTC 52035.

Spirosoma agri S7-3-3 (KCTC 52727) and Spirosoma terrae 15J9-4 (KCTC 52035) are type strains isolated from an apple orchard and beach soil in South Korea, respectively; their draft genome sequences were assembled and annotated. The draft genome sequences of S7-3-3T (7,239,915 bp; G+C content, 50.6%) and 15J9-4T (7,551,610 bp; G+C content, 47.3%) are reported.