Retrospective Cohort Study on the Impact of the COVID-19 Pandemic on Pregnancy Outcomes for Women Living With HIV in British Columbia.

BACKGROUND: For pregnant women living with HIV (WLWH), engagement in care is crucial to maternal health and reducing the risk of perinatal transmission. To date, there have been no studies in Canada examining the impact of the COVID-19 pandemic on pregnant WLWH. METHODS: This was a retrospective cohort study assessing the impact of the pandemic on perinatal outcomes for pregnant WLWH using data from the Perinatal HIV Surveillance Program in British Columbia, Canada. We compared maternal characteristics, pregnancy outcomes, and clinical indicators related to engagement with care between a prepandemic (January 2017-March 2020) and pandemic cohort (March 2020-December 2022). We investigated preterm birth rates with explanatory variables using logistic regression analysis. RESULTS: The prepandemic cohort (n = 87) had a significantly (P < 0.05) lower gestational age at the first antenatal encounter (9.0 vs 11.8) and lower rates of preterm births compared with the pandemic cohort (n = 56; 15% vs 37%). Adjusted odds of preterm birth increased with the presence of substance use in pregnancy (aOR = 10.45, 95% confidence interval: 2.19 to 49.94) in WLWH. There were 2 cases of perinatal transmission of HIV in the pandemic cohort, whereas the prepandemic cohort had none. CONCLUSIONS: The pandemic had pronounced effects on pregnant WLWH and their infants in British Columbia including higher rates of preterm birth and higher gestational age at the first antenatal encounter. The nonstatistically significant increase in perinatal transmission rates is of high clinical importance.

Systematic review of the safety, immunogenicity, and effectiveness of COVID-19 vaccines in pregnant and lactating individuals and their infants.

BACKGROUND: There is significant risk of complications and vulnerability to severe COVID-19 disease in pregnancy, yet hesitancy exists around COVID-19 vaccination during pregnancy and lactation. OBJECTIVE: To summarize the safety, immunogenicity, and effectiveness of COVID-19 vaccines in pregnancy and lactation. SEARCH STRATEGY: A systematic search of MEDLINE, Embase, PubMed, medRxiv, and bioRxiv. SELECTION CRITERIA: Identified original studies published on pregnant and/or lactating individuals who received one or more doses of a COVID-19 vaccine. DATA COLLECTION AND ANALYSIS: A descriptive summary organized by safety, immunogenicity, and effectiveness outcomes of COVID-19 vaccination in pregnancy and lactation. MAIN RESULTS: In total, 23 studies were identified. Humoral response and functional immunity were interrogated and found. Increasing placental transfer ratios in cord blood were associated with increasing time from the first vaccine dose to delivery. Safety data indicated that pregnant and lactating populations experienced vaccine-related reactions at similar rates to the general population. No increased risk of adverse obstetrical or neonatal outcomes were reported. One study demonstrated that pregnant individuals were less likely to experience COVID-19 when vaccinated. CONCLUSION: COVID-19 vaccination in pregnant and lactating individuals is immunogenic, does not cause significant vaccine-related adverse events or obstetrical and neonatal outcomes, and is effective in preventing COVID-19 disease.

Production, purification, and radiolabeling of the 203Pb/212Pb theranostic pair.

BACKGROUND: Lead-212 (212Pb, t1/2 = 10.6 h) and lead-203 (203Pb, t1/2 = 51.9 h) are an element-equivalent, or a matched theranostic radioisotope pair that show great potential for application in targeted radionuclide therapy (TRT) and single-photon emission computed tomography (SPECT), respectively. At TRIUMF we have produced both 203Pb and 212Pb using TRIUMF's TR13 (13 MeV) and 500 MeV cyclotrons, and subsequently purified and evaluated both radioisotopes using a series of pyridine-modified DOTA analogues in comparison to the commercially available chelates DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) and TCMC (1,4,7,10-tetraaza-1,4,7,10-tetra(2-carbamoylmethyl)cyclododecane). RESULTS: Proton irradiation (12.8 MeV) of natural and enriched thallium-203 (203Tl) targets gave 203Pb saturation yields of 134 ± 25 and 483 ± 3 MBq/µA, respectively. Thorium-228 (228Th, t1/2 = 1.9 y), a by-product of 232Th proton spallation on TRIUMF's main 500 MeV beamline (beamline 1A, BL1A), was recovered to build a 228Th/212Pb generator with the ability to deliver up to 9-10 MBq of 212Pb daily. Both lead isotopes were purified via solid phase extraction chromatography (Pb resin), and isolated in an acetate form ([203/212Pb]Pb(OAc)2) suitable for direct radiolabeling of chelators and bioconjugates. A series of cyclen-based chelators (herein referred to as DOTA-1Py, -2Py, and -3Py) along with established chelates DOTA and TCMC were evaluated for their ability to complex both 203Pb and 212Pb. All chelates incorporated 212Pb/203Pb efficiently, with higher radiolabeling yields observed for the 212Pb-complexes. CONCLUSION: The production of 203Pb and 212Pb was established using TRIUMF 13 MeV and 500 MeV cyclotrons, respectively. Both production methods provided radiometals suitable for subsequent radiolabeling reactions using known and novel chelates. Furthermore, the novel chelate DOTA-3Py may be a good candidate for biomolecule conjugation and further theranostic 212Pb/203Pb studies.

Risk Stratification of Prostate Cancer Through Quantitative Assessment of PTEN Loss (qPTEN).

BACKGROUND: Phosphatase and tensin homolog (PTEN) loss has long been associated with adverse findings in early prostate cancer. Studies to date have yet to employ quantitative methods (qPTEN) for measuring of prognostically relevant amounts of PTEN loss in postsurgical settings and demonstrate its clinical application. METHODS: PTEN protein levels were measured by immunohistochemistry in radical prostatectomy samples from training (n = 410) and validation (n = 272) cohorts. PTEN loss was quantified per cancer cell and per tissue microarray core. Thresholds for identifying clinically relevant PTEN loss were determined using log-rank statistics in the training cohort. Univariate (Kaplan-Meier) and multivariate (Cox proportional hazards) analyses on various subpopulations were performed to assess biochemical recurrence-free survival (BRFS) and were independently validated. All statistical tests were two-sided. RESULTS: PTEN loss in more than 65% cancer cells was most clinically relevant and had statistically significant association with reduced BRFS in training (hazard ratio [HR] = 2.48, 95% confidence interval [CI] = 1.59 to 3.87; P < .001) and validation cohorts (HR = 4.22, 95% CI = 2.01 to 8.83; P < .001). The qPTEN scoring method identified patients who recurred within 5.4 years after surgery (P < .001). In men with favorable risk of biochemical recurrence (Cancer of the Prostate Risk Assessment - Postsurgical scores <5 and no adverse pathological features), qPTEN identified a subset of patients with shorter BRFS (HR = 5.52, 95% CI = 2.36 to 12.90; P < .001) who may be considered for intensified monitoring and/or adjuvant therapy. CONCLUSIONS: Compared with previous qualitative approaches, qPTEN improves risk stratification of postradical prostatectomy patients and may be considered as a complementary tool to guide disease management after surgery.

Quantitative input-output relationships between human soleus muscle spindle afferents and motoneurons.

A method is described that, for the first time, allows instantaneous estimation of the Ia fiber input to human soleus motoneurons following electrical stimulation of the tibial nerve. The basis of the method is to determine the thresholds of the most and least excitable 1a fibers to electrical stimulation, and to treat the intervening thresholds as having a normal distribution about the mean; the validity of this approach is discussed. It was found that, for the same Ia fiber input, the percentage of soleus motoneurons contributing to the H (Hoffmann)-reflex differed considerably among subjects; when the results were pooled, however, there was an approximately linear relationship between Ia input and motoneuron output. Weak extension of the great toe diminished the soleus motoneuron reflex discharge in all but 2 of 16 subjects; the results for weak ankle plantarflexion were less consistent, but overall, there was a reduction in soleus motoneuron output also. The methodology should provide new insights into disorders of movement and tone, especially as it permits estimates of motoneuron depolarization to be made. NEW & NOTEWORTHY Assuming a normal distribution of Ia fiber thresholds to electrical stimulation and using the H-reflex, we determined for the first time an Ia input-α-motoneuron output relationship for the human soleus muscle. The relationship varies greatly among subjects but, overall, is approximately linear. Minimal contraction of a toe muscle alters the relationship dramatically, probably due to presynaptic inhibition of Ia fibers. Drawing on the literature, we can calculate changes in α-motoneuron membrane potential.

Review of renal cell carcinoma and its common subtypes in radiology.

Representing 2%-3% of adult cancers, renal cell carcinoma (RCC) accounts for 90% of renal malignancies and is the most lethal neoplasm of the urologic system. Over the last 65 years, the incidence of RCC has increased at a rate of 2% per year. The increased incidence is at least partly due to improved tumor detection secondary to greater availability of high-resolution cross-sectional imaging modalities over the last few decades. Most RCCs are asymptomatic at discovery and are detected as unexpected findings on imaging performed for unrelated clinical indications. The 2004 World Health Organization Classification of adult renal tumors stratifies RCC into several distinct histologic subtypes of which clear cell, papillary and chromophobe tumors account for 70%, 10%-15%, and 5%, respectively. Knowledge of the RCC subtype is important because the various subtypes are associated with different biologic behavior, prognosis and treatment options. Furthermore, the common RCC subtypes can often be discriminated non-invasively based on gross morphologic imaging appearances, signal intensity on T2-weighted magnetic resonance images, and the degree of tumor enhancement on dynamic contrast-enhanced computed tomography or magnetic resonance imaging examinations. In this article, we review the incidence and survival data, risk factors, clinical and biochemical findings, imaging findings, staging, differential diagnosis, management options and post-treatment follow-up of RCC, with attention focused on the common subtypes.

Multimodality Imaging Characteristics of the Common Renal Cell Carcinoma Subtypes: An Analysis of 544 Pathologically Proven Tumors.

OBJECTIVES: The objective of this study was to define the characteristic imaging appearances of the common renal cell carcinoma (RCC) subtypes. MATERIALS AND METHODS: The Institutional Review Board approval was obtained for this HIPAA-compliant retrospective study, and informed consent was waived. 520 patients (336 men, 184 women; age range, 22-88 years) underwent preoperative cross-sectional imaging of 544 RCCs from 2008 to 2013. The imaging appearances of the RCCs and clinical information were reviewed. Data analysis was performed using parametric and nonparametric statistics, descriptive statistics, and receiver operating characteristic analysis. RESULTS: The RCC subtypes showed significant differences (P < 0.001) in several imaging parameters such as tumor margins, tumor consistency, tumor homogeneity, the presence of a central stellate scar, T2 signal intensity, and the degree of tumor enhancement. Low T2 signal intensity on magnetic resonance imaging (MRI) allowed differentiation of papillary RCC from clear cell and chromophobe RCCs with 90.9% sensitivity and 93.1% specificity. A tumor-to-cortex ratio ≥1 on the corticomedullary phase had 98% specificity for clear cell RCC. CONCLUSION: The T2 signal intensity of the tumor on MRI and its degree of enhancement are useful imaging parameters for discriminating between the RCC subtypes while gross morphological findings offer additional value in RCC profiling.

Internal Carotid Artery Web: Doppler Ultrasound with CT Angiography correlation.

We present a case of an internal carotid web, detected on duplex ultrasound and confirmed by CT angiography. To our knowledge, this is only the third reported ultrasound case in the imaging literature. This vascular abnormality can cause a clinically significant carotid stenosis and is a risk factor for recurrent embolic cerebrovascular events. Due to small size and poor awareness among radiologists, carotid webs are often under-diagnosed on non-invasive imaging modalities. Improved awareness including knowledge of salient imaging features is useful as early diagnosis leading to appropriate intervention can eliminate the risk of future cerebrovascular events.

Effect of an emergency department sepsis protocol on the care of septic patients admitted to the intensive care unit.

OBJECTIVE: We sought to determine whether the implementation of a sepsis protocol in a Canadian emergency department (ED) improves care for the subset of patients admitted to the intensive care unit (ICU). METHODS: After implementing a sepsis protocol in our ED we used an ICU database and chart review to compare various time-dependent end points and outcomes between a historical control year and the first year after implementation. We re-viewed the charts of all patients admitted to the ICU within 24 hours of ED admission with a primary or other diagnosis of sepsis, severe sepsis or septic shock, who met criteria for early goal-directed therapy within the first 6 hours of their ED stay. RESULTS: We compared 29 patients from the control year with 30 patients from the year after implementation of our sepsis protocol. We found that patients treated during the postintervention year had improvements in time to antibiotics (4.2 v. 1.0 h, difference = -3.2 h, 95% CI -4.8 to -2.0), time to central line placement (above the diaphragm) (11.6 v. 3.2 h, difference = -8.4 h, 95% CI -12.1 to -4.7), time to arterial line placement (7.5 v. 2.3 h, difference = -5.2 h, 95% CI -7.4 to -3.0), and achievement of central venous pressure and central venous oxygen saturation goals (11.1 v. 5.1 h, difference = -6.0 h, 95% CI -11.03 to -1.71, and 13.1 v. 5.5 h, difference = -7.6 h, 95% CI -11.97 to -3.16, respectively). There were no statistically significant differences in ICU length of stay, hospital length of stay or mortality (31.0% v. 20.0%, difference = -11.0%, 95% -33.1% to 11.1%). CONCLUSION: Implementation of an ED sepsis protocol im-proves care for patients with severe sepsis and septic shock.

Speculations surrounding a spinal reflex.

A method has been developed for measuring the Ia fibre input/motoneurone output relationship for the soleus H-reflex in healthy human volunteers. The shift in the relationship during weak toe extension, and in some subjects during weak plantar flexion, indicates the imposition of an inhibitory mechanism, presumably presynaptic. From these observations, and others previously made on long-loop reflexes, it is argued that the inhibitory mechanism may have evolved to suppress unwanted information from the periphery, not only during movement but in the resting state, and that this development was a necessary accompaniment of encephalisation.

Tendon reflexes elicited using a computer controlled linear motor tendon hammer.

We present a novel instrumentation system for studying tendon and spinal reflexes using a commercial linear servo-motor as a precisely controlled tendon hammer. The system uses a LabVIEW-based program to both control electrical or mechanical stimuli and record and measure the resulting M and H waves. The hammer can deliver tendon taps with selected velocities, durations, frequencies and excursions. Preliminary results for both soleus and flexor carpi radialis muscles show that impact velocity is an important variable in eliciting tendon reflexes. As expected, the tendon reflex amplitude was also found to be dependent on excursion depth, but not as significantly as hammer velocity. Other stimulus paradigms are also presently being investigated.