Geometric morphometric analysis of the brainstem and cerebellum in Chiari I malformation.

Background: Chiari I malformation (CMI) is characterized by inferior descent of the cerebellar tonsils through the foramen magnum and is associated with headache and neck pain. Many morphometric research efforts have aimed to describe CMI anatomy in the midsagittal plane using classical measurement techniques such as linear dimensions and angles. These methods are less frequently applied to parasagittal features and may fall short in quantifying more intricate anatomy with fewer distinct homologous landmarks. Methods: Landmark-based geometric morphometric techniques were used to asses CMI morphology in five anatomical planes of interest. Results: Significant shape differences between CMI and age/sex-matched controls were found in the midsagittal (Pseudo-F = 5.4841, p = 0.001) and axial planes through the rostral medulla (Pseudo-F = 7.6319, p = 0.001). In addition to tonsillar descent, CMI principal component 1 (PC1) scores in the midsagittal protocol were associated with marked anterior concavity of the brainstem and generalized verticality of the cerebellum with anterior rotation of its anterior lobe. In the axial medulla/cerebellum protocol, CMI PC1 scores were associated with greater anterior-posterior (A-P) dimension with loss of medial-lateral (M-L) dimension. Discussion: These results suggest that CMI is associated with greater curvature of the brainstem and spinal cord, which may perturb normal neural activities and disrupt cerebrospinal fluid movements. Previous reports on the A-P diameter of the posterior fossa in CMI have conflicted; our findings of greater A-P cerebellar dimensionality with concomitant loss of width alludes to the possibility that more caudal aspects of the posterior cranial fossa are more bowl-like (homogenous in axial dimensions) and less trough-like or elongated in the M-L direction.

Outcomes of Patients Living with HIV Hospitalized due to COVID-19: A 3-Year Nationwide Study (2020-2022).

Scientific reports on the association between human immunodeficiency virus (HIV) in patients with COVID-19 and mortality have not been in agreement. In this nationwide study, we described and analyzed the demographic and clinical characteristics of people living with HIV (PLWH) and established that HIV infection is a risk factor for mortality in patients hospitalized due to COVID-19. We collected data from the National Hospital Data Information System at Hospitalization between 2020 and 2022. We included patients admitted to the hospital with a diagnosis of COVID-19. We established a cohort of patients with PLWH and compared them to patients without HIV (non-PLWH). For multivariate analyses, we performed binary logistic regression, using mortality as the dependent variable. To improve the interpretability of the results we also applied penalized regression and random forest, two well-known machine-learning algorithms. A broad range of comorbidities, as well as sex and age data, were included in the final model as adjusted estimators. Our data of 1,188,160 patients included 6,973 PLWH. The estimated hospitalization rate in this set was between 1.43% and 1.70%, while the rate among the general population was 0.83%. Among patients with COVID-19, HIV infection was a risk factor for mortality with an odds ratio (OR) of 1.25 (95% CI, 1.14-1.37, p < 0.001). PLWH are more likely to be hospitalized due to COVID-19 than are non-PLWH. PLWH are 25% more likely to die due to COVID-19 than non-PLWH. Our results highlight that PLWH should be considered a population at risk for both hospitalization and mortality.

Connecting impaired fibrinolysis and dyslipidemia.

A State of the Art lecture entitled "Connecting Fibrinolysis and Dyslipidemia" was presented at the International Society on Thrombosis and Haemostasis Congress 2023. Hemostasis balances the consequences of blood clotting and bleeding. This balance relies on the proper formation of blood clots, as well as the breakdown of blood clots. The primary mechanism that breaks down blood clots is fibrinolysis, where the fibrin net becomes lysed and the blood clot dissolves. Dyslipidemia is a condition where blood lipid and lipoprotein levels are abnormal. Here, we review studies that observed connections between impaired fibrinolysis and dyslipidemia. We also summarize the different correlations between thrombosis and dyslipidemia in different racial and ethnic groups. Finally, we summarize relevant and new findings on this topic presented during the 2023 International Society on Thrombosis and Haemostasis Congress. More studies are needed to investigate the mechanistic connections between impaired fibrinolysis and dyslipidemia and whether these mechanisms differ in racially and ethnically diverse populations.

Clot or Not? Reviewing the Reciprocal Regulation Between Lipids and Blood Clotting.

Both hyperlipidemia and thrombosis contribute to the risks of atherosclerotic cardiovascular diseases, which are the leading cause of death and reduced quality of life in survivors worldwide. The accumulation of lipid-rich plaques on arterial walls eventually leads to the rupture or erosion of vulnerable lesions, triggering excessive blood clotting and leading to adverse thrombotic events. Lipoproteins are highly dynamic particles that circulate in blood, carry insoluble lipids, and are associated with proteins, many of which are involved in blood clotting. A growing body of evidence suggests a reciprocal regulatory relationship between blood clotting and lipid metabolism. In this review article, we summarize the observations that lipoproteins and lipids impact the hemostatic system, and the clotting-related proteins influence lipid metabolism. We also highlight the gaps that need to be filled in this area of research.

Plasma tissue-type plasminogen activator is associated with lipoprotein(a) and clinical outcomes in hospitalized patients with COVID-19.

Background: Patients with COVID-19 have a higher risk of thrombosis and thromboembolism, but the underlying mechanism(s) remain to be fully elucidated. In patients with COVID-19, high lipoprotein(a) (Lp(a)) is positively associated with the risk of ischemic heart disease. Lp(a), composed of an apoB-containing particle and apolipoprotein(a) (apo(a)), inhibits the key fibrinolytic enzyme, tissue-type plasminogen activator (tPA). However, whether the higher Lp(a) associates with lower tPA activity, the longitudinal changes of these parameters in hospitalized patients with COVID-19, and their correlation with clinical outcomes are unknown. Objectives: To assess if Lp(a) associates with lower tPA activity in COVID-19 patients, and how in COVID-19 populations Lp(a) and tPA change post infection. Methods: Endogenous tPA enzymatic activity, tPA or Lp(a) concentration were measured in plasma from hospitalized patients with and without COVID-19. The association between plasma tPA and adverse clinical outcomes was assessed. Results: In hospitalized patients with COVID-19, we found lower tPA enzymatic activity and higher plasma Lp(a) than that in non-COVID-19 controls. During hospitalization, Lp(a) increased and tPA activity decreased, which associates with mortality. Among those who survived, Lp(a) decreased and tPA enzymatic activity increased during recovery. In patients with COVID-19, tPA activity is inversely correlated with tPA concentrations, thus, in another larger COVID-19 cohort, we utilized plasma tPA concentration as a surrogate to inversely reflect tPA activity. The tPA concentration was positively associated with death, disease severity, plasma inflammatory, and prothrombotic markers, and with length of hospitalization among those who were discharged. Conclusion: High Lp(a) concentration provides a possible explanation for low endogenous tPA enzymatic activity, and poor clinical outcomes in patients with COVID-19.

Intracellular tPA-PAI-1 interaction determines VLDL assembly in hepatocytes.

Apolipoprotein B (apoB)-lipoproteins initiate and promote atherosclerotic cardiovascular disease. Plasma tissue plasminogen activator (tPA) activity is negatively associated with atherogenic apoB-lipoprotein cholesterol levels in humans, but the mechanisms are unknown. We found that tPA, partially through the lysine-binding site on its Kringle 2 domain, binds to the N terminus of apoB, blocking the interaction between apoB and microsomal triglyceride transfer protein (MTP) in hepatocytes, thereby reducing very-low-density lipoprotein (VLDL) assembly and plasma apoB-lipoprotein cholesterol levels. Plasminogen activator inhibitor 1 (PAI-1) sequesters tPA away from apoB and increases VLDL assembly. Humans with PAI-1 deficiency have smaller VLDL particles and lower plasma levels of apoB-lipoprotein cholesterol. These results suggest a mechanism that fine-tunes VLDL assembly by intracellular interactions among tPA, PAI-1, and apoB in hepatocytes.

The correlations among racial/ethnic groups, hypertriglyceridemia, thrombosis, and mortality in hospitalized patients with COVID-19.

Reports of racial and ethnic disparities regarding both rates of infection of the SARS-CoV-2 virus and morbidity of the coronavirus disease-19 (COVID-19) contain profound differences depending on the population. Our previous study has shown that patients with COVID-19 who developed hypertriglyceridemia during hospitalization have a 2.3 times higher mortality rate. However, whether the correlation between hypertriglyceridemia and mortality has disparity among different racial and ethnic groups is unknown. In this study, we investigated the impact of race/ethnicity on the correlation between hypertriglyceridemia and mortality in hospitalized patients with COVID-19. De-identified information from 904 hospitalized patients diagnosed with COVID-19 between March 2020 and June 2021 were extracted from the Medical College of Wisconsin Clinical Data Warehouse. A multivariable regression analysis suggested that the Asians and non-White Hispanics had 4 or 3.9 times higher mortality rate, respectively, after adjusting for age, morbid obesity (BMI ≥40), and gender. The hypertriglyceridemia (≥150 mg/dL) was associated with higher mortality, after adjusting for age, gender, and morbid obesity. The baseline hypertriglyceridemia occurrence had relevantly more consistent percentages among all racial/ethnic groups. However, non-White Hispanic and Asian patients had the highest frequencies of peak hypertriglyceridemia occurrence during hospitalization. The peak hypertriglyceridemia developed during hospitalization correlates with the incidence of thrombosis after adjusting for morbid obesity, age, and sex. In summary, in this retrospective study of 904 hospitalized COVID-19 patients, Asians and non-White Hispanics had a greater likelihood of developing hypertriglyceridemia during hospitalization and mortality than White patients.

Delayed Diagnosis of an Atypical Pneumonia Resembling a Solitary Pulmonary Nodule.

Atypical pneumonia shows clinical features that are different from those of typical pneumonia, and it can mimic other entities. We report the case of a 42-year-old male with a solitary pulmonary nodule found in an X-ray for a preoperative evaluation. Our patient was asymptomatic, and a pulmonary neoplasm was the first diagnostic suspicion. The round-shaped nodule seen in the X-ray turned out to be a linear ground glass opacity in a thoracic CT scan. Viral pneumonia due to SARS-CoV-2 was diagnosed. We emphasize here the educational value of this case report. We do not report a new radiological finding because lung nodules resembling neoplasms have already been reported in the medical literature. However, some clinical features of COVID-19 are relatively new and can mimic other entities, and the results of some investigations and clinicians' interpretations of them can be misleading. Atypical radiological findings make it necessary to widen the spectrum of alternative diagnoses.

Bacteraemia and liver abscess due to Fusobacterium necrophorum.

Fusobacterium necrophorum is the oropharyngeal pathogen usually associated with Lemierre's syndrome, a pharyngeal infection which evolves to sepsis, septic emboli and thrombophlebitis of the adjacent neck vessels. It is an uncommon causative bacteria of a liver abscess, and an extensive workup should, therefore, be performed in order to rule out potential sources of the infection. This case report describes the workup that led to the diagnosis of a colorectal carcinoma, which was deemed to be the source of the Fusobacterium bacteraemia.

Non-surgical treatment of a relapsed cystic hygroma in an adult.

Lymphatic malformations, also known as lymphangiomas or cystic hygromas, are benign masses that typically affect newborns and infants and involve the head and neck regions. They are, however, rare in adults and even rarer in the axillary region. Although surgery is considered to be the treatment of choice, we present a rare case of a recurrent cystic hygroma 32 years after the first surgical operation. Due to the cosmetic concerns and the risks of a surgical approach, non-surgical therapy with percutaneous sclerosants was performed, with a good outcome after a 2-year follow-up period.

[Hypokalemia, a key clinical data for diagnosing primary hyperaldosteronism]. / Hipopotasemia, dato clínico clave en el diagnóstico de un hiperaldosteronismo primario.

We report a case of a 37 year-old man with a long history of hypertension under treatment, who was admitted at our institution with intense fatigue and weakness of lower limbs. The laboratory results at Emergency Department showed severe hypokalemia. A study of secondary hypertension was carried out. With the initial suspicion of primary hyperaldosteronism, complete blood test was done including plasma renine activity, which was completely suppressed, and plasma aldosterone concentration, which resulted normal. Likewise, an abdomen CT was performed and revealed a left adrenal mass consistent of suprarrenal adenoma. Therefore, a salt loading suppression test was done with subsequent measure of plasmatic renine activity, which was still suppressed, plasma aldosterone concentration, that persisted normal, and a 24-h urinary aldosterone excretion rate, which was clearly high, supporting the suspected diagnosis. After the adrenalectomy, the patient remained asymptomatic with normal blood pressure without treatment and with normal serum potassium levels.

REPRODUCTIVE NEOPLASMS IN WILD AND LONG-TERM CAPTIVE FEMALE FLORIDA MANATEES (TRICHECHUS MANATUS LATIROSTRIS).

Few reports of neoplastic diseases in manatees exist in the veterinary literature. This case series presents reproductive neoplasia noted in eight wild and long-term captive female Florida manatees (Trichechus manatus latirostris) obtained through carcass recovery and animal rehabilitation programs between April 2009 and May 2014. All cases were evaluated histologically, and diagnoses of uterine carcinoma (n = 1), granulosa cell tumor (n = 2), ovarian adnexal tumor (n = 1), and leiomyoma (n = 5) were made. The underlying cause of tumor development and effects on reproductive success is currently unknown, but possible asymmetric reproductive aging and/or a correlation between obesity and reproductive disorder in long-term nonreproductive female manatees are of interest and warrant further investigation.

Risk factors associated with cataracts and lens luxations in captive pinnipeds in the United States and the Bahamas.

OBJECTIVE: To determine risk factors for lens luxation and cataracts in captive pinnipeds in the United States and the Bahamas. DESIGN: Cross-sectional study. ANIMALS: 111 pinnipeds (99 California sea lions [Zalophus californianus], 10 harbor seals [Phoca vitulina], and 2 walruses [Odobenus rosmarus]) from 9 facilities. PROCEDURES: Eyes of each pinniped were examined by a veterinary ophthalmologist for the presence of cataracts or lens luxations and photographed. Information detailing husbandry practices, history, and facilities was collected with a questionnaire, and descriptive statistical analyses were performed for continuous and categorical variables. Odds ratios and associated 95% confidence intervals were estimated from the final model. RESULTS: Risk factors for lens luxation, cataracts, or both included age >or= 15 years, history of fighting, history of ocular disease, and insufficient access to shade. CONCLUSIONS AND CLINICAL RELEVANCE: Diseases of the lens commonly affect captive pinnipeds. Access to UV-protective shade, early identification and medical management of ocular diseases, and prevention of fighting can limit the frequency or severity of lens-related disease in this population. An extended life span may result from captivity, but this also allows development of pathological changes associated with aging, including cataracts.

Monoclonal antibodies to the recombinant protein TmpA of the Treponema pallidum.

Spleen cells from BALB/c mice immunized with recombinant TmpA were fused with mouse myeloma cells (P3/X63-Ag8), and five hybridomas secreting monoclonal antibodies were obtained. These hybridomas specifically recognize TmpA and do not cross-react with other molecules such as recombinant HBsAg of HBV and synthetic HCV core peptides. The monoclonal antibodies were IgG1 subclass and ascitic fluid from these hybridomas was purified by affinity chromatography on Protein A-Sepharose CL-4B column to isolate the IgG1 active fraction. The affinity constant of these monoclonal antibodies ranged from 6.4 x 10(8) and 1.73 x 10(10) M(-1).

Papillary thyroid cancer in Mexico: review of 409 cases.

This is a retrospective review of 409 cases of papillary thyroid cancer treated at the Hospital of Oncologia, National Medical Center, IMSS in Mexico City. The clinical features, histopathologic findings, analysis of recurrences and survivals according to age, sex, tumor size, and modality of treatment are described. The results showed that tumoral diameter > 5 cm, distant metastasis at diagnosis, age > 40 years, and tumoral infiltration beyond the thyroid capsule significantly affect the patient's survival.