Impact of hypercalcemia and parathyroid hormone level on the sensitivity of preoperative sestamibi scanning for primary hyperparathyroidism

Technetium 99m sestamibi scanning (MIBI) can direct unilateral parathyroidectomy. However, the clinical application remains variable with sensitivities ranging from 55 to 100 per cent. We examined whether patient factors including serum calcium (Ca) and parathyroid hormone (PTH) levels impact the sensitivity of MIBI. We completed a retrospective review of 102 patients with primary hyperparathyroidism and mild hypercalcemia who underwent preoperative MIBI. All patients underwent bilateral neck explorations with abnormalities confirmed by histopathology. MIBI sensitivity was correlated with preoperative Ca and PTH levels using univariate and logistic regression analysis. The mean preoperative Ca was 11.0 mg/dL and the mean PTH was 158 pg/mL. More than 95 per cent of patients with Ca greater than 11.3 mg/dL had a positive scan as compared with 60 per cent of those with lesser values (P = 0.0024). Similarly a serum PTH level greater than 160 pg/mL correlated with positive scans in 93 per cent as opposed to 57 per cent in those with lower levels (P = 0.006). Using a scan-directed approach 65 of 74 patients would have undergone unilateral exploration; this would yield a 7.7 per cent operative failure rate because of contralateral multigland disease. Lower Ca and PTH levels seem to correlate with reduced sensitivity of MIBI. Increasing acceptance of surgery for hyperparathyroidism with minimal hypercalcemia may make MIBI less attractive without ancillary diagnostic measures such as rapid parathormone assays.     

Postoperative surveillance of differentiated thyroid carcinoma: a selective approach

This review was conducted to evaluate the selective use of 131I whole-body scanning (WBS) and radioablation (RA) after thyroidectomy for patients with differentiated thyroid carcinoma (DTC). A review of patients undergoing thyroidectomy for DTC between July 1, 1980 and December 31, 1999 was performed. Postoperative surveillance involved a selective RA protocol based on a modification of the AMES criteria (age, metastases, extent of cancer, size, and multifocality of tumor). Lower-risk patients were followed by yearly thyroglobulin (Tg) levels and physical examinations (PE) whereas higher-risk patients additionally underwent WBS and RA when appropriate. Three hundred forty-three patients were identified; of these 27 per cent had positive lymph nodes or metastatic disease at their initial operation. Two hundred thirteen (64%) patients underwent postoperative WBS with 174 (82%) requiring RA. One hundred thirty (36%) low-risk patients were followed with yearly Tg and PE that when abnormal led to WBS and RA. No additional patient morbidity or mortality resulted from this protocol. Factors identified during multivariate analyses as being predictive of occult metastasis and recurrence (P < 0.05) included tumor size and lymph node status. These data support a selective approach to the postoperative surveillance of DTC using Tg and PE to monitor low-risk patients and WBS for those with a higher risk of recurrence.     

Adrenal insufficiency in patients with ruptured abdominal aortic aneurysms

PURPOSE: Failure of the adrenocortical system after open repair of ruptured abdominal aortic aneurysm (RAAA) has never been reported, to our knowledge. This study was undertaken to examine the incidence and response to treatment of adrenal insufficiency in the RAAA population. METHODS: A 6-year retrospective analysis was carried out on data for all patients admitted after RAAA repair. A cosyntropin stimulation test (CST) was performed in patients with unexplained postoperative hypotension. Patients with adrenal insufficiency were given stress dose hydrocortisone, followed by slow hydrocortisone taper. RESULTS: Twenty of 26 patients admitted after RAAA repair survived longer than 1 week. Nine of these 20 patients underwent CST because of unexplained hypotension, and six patients were found to have adrenal insufficiency. Compared with the three patients with normal CST and the 11 patients with normotension who did not require testing, patients with adrenal insufficiency had greater preoperative hypotension (83% vs 29%; P =.05), greater operative blood loss (7.0 +/- 1.6 L vs 3.0 +/- 0.9 L; P =.003), longer lower extremity ischemia time (5.0 +/- 2.3 hours vs 1.3 +/- 0.5 hours; P =.025), and lower intraoperative urine output (0.8 +/- 0.4 mL/kg/hr vs 2.1 +/- 0.6 mL/kg/hr; P =.023). No difference in length of stay (40 +/- 18 days vs 35 +/- 26 days), major complications (27% vs 32%), or overall mortality (17% vs 15%) was demonstrated with steroid therapy. Initiation of steroid therapy enabled weaning of vasopressor support within 48 hours in patients with adrenal insufficiency. CONCLUSIONS: Adrenal insufficiency was identified in 67% of patients with RAAA with unexplained postoperative hypotension given a CST. Predictors of adrenal insufficiency after RAAA repair include preoperative hypotension and a complicated operative course. Steroid therapy can limit vasopressor dependence, and is not associated with increased morbidity or mortality.     

Apolipoprotein E genotype is associated with temporal and hippocampal atrophy rates in healthy elderly adults: a tensor-based morphometry study

Apolipoprotein E (ApoE) ε4 genotype is a strong risk factor for developing Alzheimer's disease (AD). Conversely, the presence of the ε2 allele has been shown to mitigate cognitive decline. Tensor-based morphometry (TBM), a novel computational approach for visualizing longitudinal progression of brain atrophy, was used to determine whether cognitively intact elderly participants with the ε4 allele demonstrate greater volume reduction than those with the ε2 allele. Healthy "younger elderly" volunteers, aged 55-75, were recruited from the community and hospital staff. They were evaluated with a baseline and follow-up MRI scan (mean scan interval = 4.72 years, s.d. = 0.55) and completed ApoE genotyping. Twenty-seven participants were included in the study of which 16 had the ε4 allele (all heterozygous ε3ε4 genotype) and 11 had the ε2ε3 genotype. The two groups did not differ significantly on any demographic characteristics and all subjects were cognitively "normal" at both baseline and follow-up time points. TBM was used to create 3D maps of local brain tissue atrophy rates for individual participants; these spatially detailed 3D maps were compared between the two ApoE groups. Regional analyses were performed and the ε4 group demonstrated significantly greater annual atrophy rates in the temporal lobes (p = 0.048) and hippocampus (p = 0.016); greater volume loss was observed in the right hippocampus than the left. TBM appears to be useful in tracking longitudinal progression of brain atrophy in cognitively asymptomatic adults. Possession of the ε4 allele is associated with greater temporal and hippocampal volume reduction well before the onset of cognitive deficits.     

Evaluation of vascular injury in penetrating extremity trauma: angiographers stay home

The debate over the use of diagnostic angiography (DA) to exclude arterial injury in penetrating extremity trauma (PET) continues. This review evaluates our current protocol for PET and identifies indications for DA. Patients presenting to our urban Level I trauma center between January 1997 and September 2000 with PET were included. Demographic data, emergency department (ED) course, and patient follow-up were reviewed. ED evaluation directed by physical examination (PE) included Doppler pressure indices (DPI) and DA if indicated. A total of 538 patients had PET injuries. Twenty (4%) patients with hard signs of vascular injury were taken to the operating room. Ninety-one (17%) patients without vascular compromise underwent operative procedures or were admitted for other injuries. One hundred twenty-three (23%) patients with nonproximity wounds were discharged. Four DAs were performed for abnormal DPI with no change in management. Three hundred patients with a negative PE and normal DPI were discharged from the ED. Follow-up was available on 51 per cent of these patients (range 1-49 months) with no missed injuries identified. We conclude that PE with DPI is an appropriate way to identify significant vascular injuries from PET. Patients with normal PE and DPI can be safely discharged. DA is only indicated for asymptomatic patients with abnormal DPI.     

Tropism of SARS-CoV-2 for human cortical astrocytes

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) readily infects a variety of cell types impacting the function of vital organ systems, with particularly severe impact on respiratory function. Neurological symptoms, which range in severity, accompany as many as one-third of COVID-19 cases, indicating a potential vulnerability of neural cell types. To assess whether human cortical cells can be directly infected by SARS-CoV-2, we utilized stem-cell-derived cortical organoids as well as primary human cortical tissue, both from developmental and adult stages. We find significant and predominant infection in cortical astrocytes in both primary tissue and organoid cultures, with minimal infection of other cortical populations. Infected and bystander astrocytes have a corresponding increase in inflammatory gene expression, reactivity characteristics, increased cytokine and growth factor signaling, and cellular stress. Although human cortical cells, particularly astrocytes, have no observable ACE2 expression, we find high levels of coronavirus coreceptors in infected astrocytes, including CD147 and DPP4. Decreasing coreceptor abundance and activity reduces overall infection rate, and increasing expression is sufficient to promote infection. Thus, we find tropism of SARS-CoV-2 for human astrocytes resulting in inflammatory gliosis-type injury that is dependent on coronavirus coreceptors.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the life-threatening illness COVID-19 and is responsible for a global pandemic resulting in more than 5.8 million deaths worldwide. Although SARS-CoV-2 infection can cause catastrophic, life-threatening damage to respiratory function, the capacity to infect other cell types and disrupt function of additional organ systems is a subject of intense study. Strikingly, many patients suffering with or having recovered from COVID-19 present with a range of neurological symptoms including seizures; encephalopathy; stroke; headaches; dizziness; short-term memory loss; loss of smell and taste; confusion; a general inability to focus; and new or recurring neuropsychiatric symptoms, like anxiety and depression (1–5). As many as one-third of individuals, 6 mo after recovering from COVID-19 infection, are diagnosed with neurological or neuropsychiatric conditions (6). Additionally, individuals with mental health diagnoses are more susceptible to coronavirus infection and have impaired long-term health outcomes (7).It is unclear whether the range of neurological symptoms are a result of direct infection of the neural tissue or a secondary consequence of widespread inflammation downstream of viral infection in other tissues. Several studies have demonstrated how inflammation contributes to systemic problems in a variety of organ systems, including the central nervous system (CNS) (8, 9). However, SARS-CoV-2 can infect neurons in the nasal epithelium, a potential mode of entry to the CNS from the periphery, and the presence of viral RNA has been detected in neural tissues in patients (10). Recent studies report mixed findings regarding the presence of coronavirus viral RNA and antibodies in the cerebral spinal fluid (CSF) of COVID-19 patients (3, 8, 11, 12). However, choroid plexus organoids containing the cell type that produces CSF can be readily infected by SARS-CoV-2 in vitro (13, 14), suggesting possible viral access to CSF. Additionally, the virus can infect and disrupt brain vasculature. Studies of postmortem brain tissue from severely infected COVID-19 patients have reported widespread inflammation in the brainstem, choroid plexus, and brain parenchyma characterized by infiltration of immune cells including microglia and T cells, as well as infection of cranial nerves, microvascular injury, fibrinogen leakage, and extensive astrogliosis (8, 15, 16). Together, these studies suggest the capacity for viral transmission into the CNS through leaky vasculature, the nasal epithelium, and/or CSF.The vulnerability of particular cell types in the brain and the impact on neurological health and function require in-depth study, and human stem-cell-derived neural models have been utilized to evaluate viral tropism (17, 18). Studies of cerebral organoids, which are reflective of developmental stages, suggest that in vitro neurons may be vulnerable to SARS-CoV-2 infection. However, reports regarding susceptibility of neurons from different brain regions have been mixed across organoid studies (13, 14, 19). Recently, studies have begun to explore the vulnerability of nonneuronal populations, including vascular pericytes and glial cells, using stem-cell-derived organoid and assembloid models (20, 21). Additionally, studies exploring the loss of smell identified viral tropism of nonneural support cells and vascular cells in the olfactory epithelium (22). Here, we utilized primary cortical tissue from both the developing and the adult brain, paired with cortical organoid models across neurogenic and gliogenic stages, to evaluate which human neural cell types can be directly infected by SARS-CoV-2 and at what stages of maturation. In primary cortical tissue cultures and cortical organoids exposed to SARS-CoV-2, we observed significant infection and viral replication in immature and mature astrocytes but minimal infection in other neural cell types. As a response to infection, we observed widespread inflammation, cytokine secretion, and reactivity in astrocytes. However, cortical astrocytes do not express observable levels of ACE2, the canonical SARS-CoV-2 receptor, suggesting that the virus may use another means of entry. We observed that SARS-CoV-2 cofactors CD147 and DPP4 are highly expressed in infected astrocytes. Reducing the abundance of CD147 or the activity of DPP4 reduced infection, whereas increasing expression of these receptors promoted infection, suggesting a role in viral entry or propagation. Our study provides evidence of SARS-CoV-2 tropism for human astrocytes with implications for the cellular vulnerability of the human brain and downstream consequences to neurological function.