A prospective randomized trial comparing image quality,study interpretability,and radiation dose of narrow acquisition window with widened acquisition window protocols in prospectively ECG-triggered coronary computed tomography angiography

BackgroundProspectively triggered coronary computed tomography angiography (CTA) is commonly performed with a widened acquisition window to provide flexibility in image reconstruction.ObjectiveWe conducted a randomized controlled trial to determine whether the use of a narrow acquisition window in prospectively triggered coronary CTA would allow lower radiation dose while preserving image quality and interpretability.MethodsProspective 2-center 2- platform randomized trial that evaluated 205 consecutive patients 96 with widened acquisition (WA) and 109 narrow acquisition (NA) referred for coronary CTA in sinus rhythm and heart rate <65 beats/min. Patients scanned with WA had phases reconstructed at 5% intervals, and each phase was assigned an individual study ID. Images were reviewed with individual phase reconstructions interpreted randomly by 2 level 3 readers with a third for consensus. Images were evaluated with a 5-point Likert scale on a per-vessel basis (best score on any phase). Scores were then dichotomized into diagnostic (score 3–5) compared with nondiagnostic (score 1–2). Readers also reported obstructive coronary artery disease on a per-patient basis. Agreement for the diagnosis of obstructive disease and per-artery interpretability was performed. Signal and noise measurements were also performed.ResultsNo difference in demographics between groups (P = NS). The signal-to-noise ratio was comparable 12.99 ± 3.4 NA and 12.53 ± 4.13 for the WA (P = 0.45). The median effective dose was 1.78 mSv for NA compared with 3.26 mSv for WA (P < 0.001). Image quality, diagnostic interpretability, interreader agreement, and downstream testing were not significantly different between the 2 groups (P= NS for all).ConclusionsCoronary CTA with NA resulted in a 47% lower radiation dose without significant difference in study interpretability or image quality or increased downstream resource use or testing.     

Time-dependent sensory nerve ingrowth into a bone conduction chamber

We studied time-dependent ingrowth of sensory nerve fibers into a bone defect in a rat bone conduction chamber model. In 10 male Sprague Dawley rats, a titanium chamber was implanted bilaterally in the proximal tibiae, representing an experimental bone defect. To mimic a clinical situation, the chambers were filled with a fresh blood clot. After 1, 2, 4, 6 and 8 weeks, 2 rats were fixed in vivo at each time before removal of specimens, and histological and immunohistochemical analyses. We used antisera against protein gene product 9.5, neural growth-associated protein 43/B-50, calcitonin gene-related peptide, and substance P, to locate regenerating sensory nerve fibers in the chamber. During bone defect healing, hematoxylin/eosin sections showed that new bone grew in through the ingrowth openings in the chamber, gradually filling it and replacing the blood clot. At 1 and 2 weeks after implantation, no nerve fibers could be detected. At 4, 6 and 8 weeks, however, small numbers of nerve fibers were seen in 8 of 11 specimens. The nerve fibers were located mainly in the dense fibrous tissue in close proximity to the new bone, and in some cases within the new forming bone. In this chamber model, the periosteum is not in contact with the bone ingrowth openings, and all ingrowing nerve fibers thus originated from the cortical bone, endosteum or bone marrow. We speculated that these late ingrowing sensory nerve fibers may actively participate in bone repair.     

Threat-related amygdala functional connectivity is associated with 5-HTTLPR genotype and neuroticism

Communication between the amygdala and other brain regions critically regulates sensitivity to threat, which has been associated with risk for mood and affective disorders. The extent to which these neural pathways are genetically determined or correlate with risk-related personality measures is not fully understood. Using functional magnetic resonance imaging, we evaluated independent and interactive effects of the 5-HTTLPR genotype and neuroticism on amygdala functional connectivity during an emotional faces paradigm in 76 healthy individuals. Functional connectivity between left amygdala and medial prefrontal cortex (mPFC) and between both amygdalae and a cluster including posterior cingulate cortex, precuneus and visual cortex was significantly increased in 5-HTTLPR S′ allele carriers relative to L_AL_A individuals. Neuroticism was negatively correlated with functional connectivity between right amygdala and mPFC and visual cortex, and between both amygdalae and left lateral orbitofrontal (lOFC) and ventrolateral prefrontal cortex (vlPFC). Notably, 5-HTTLPR moderated the association between neuroticism and functional connectivity between both amygdalae and left lOFC/vlPFC, such that S′ carriers exhibited a more negative association relative to L_AL_A individuals. These findings provide novel evidence for both independent and interactive effects of 5-HTTLPR genotype and neuroticism on amygdala communication, which may mediate effects on risk for mood and affective disorders.     

COVID-19 vaccine effectiveness by HIV status and history of injection drug use: a test-negative analysis

Introduction

People living with HIV (PLWH) and/or who inject drugs may experience lower vaccine effectiveness (VE) against SARS-CoV-2 infection.

Methods

A validated algorithm was applied to population-based, linked administrative datasets in the British Columbia COVID-19 Cohort (BCC19C) to ascertain HIV status and create a population of PLWH and matched HIV-negative individuals. The study population was limited to individuals who received an RT-PCR laboratory test for SARS-CoV-2 between 15 December 2020 and 21 November 2021 in BC, Canada. Any history of injection drug use (IDU) was ascertained using a validated administrative algorithm. We used a test-negative study design (modified case−control analysis) and multivariable logistic regression to estimate adjusted VE by HIV status and history of IDU.

Results

Our analysis included 2700 PLWH and a matched population of 375,043 HIV-negative individuals, among whom there were 351 and 103,049 SARS-CoV-2 cases, respectively. The proportion of people with IDU history was much higher among PLWH compared to HIV-negative individuals (40.7% vs. 4.3%). Overall VE during the first 6 months after second dose was lower among PLWH with IDU history (65.8%, 95% CI = 43.5–79.3) than PLWH with no IDU history (80.3%, 95% CI = 62.7–89.6), and VE was particularly low at 4–6 months (42.4%, 95% CI = −17.8 to 71.8 with IDU history vs. 64.0%; 95% CI = 15.7–84.7 without), although confidence intervals were wide. In contrast, overall VE was 88.6% (95% CI = 88.2–89.0) in the matched HIV-negative population with no history of IDU and remained relatively high at 4–6 months after second dose (84.6%, 95% CI = 83.8–85.4). Despite different patterns of vaccine protection by HIV status and IDU history, peak estimates were similar (≥88%) across all populations.

Conclusions

PLWH with a history of IDU may experience lower VE against COVID-19 infection, although findings were limited by a small sample size. The lower VE at 4–6 months may have implications for booster dose prioritization for PLWH and people who inject drugs. The immunocompromising effect of HIV, substance use and/or co-occurring comorbidities may partly explain these findings.     

Bioimpedance as a measure of fluids in patients with septic shock. A prospective observational study

Background

Septic shock is often treated with aggressive fluid resuscitation leading to profound fluid overload. The assessment of fluid status relies on suboptimal measures making treatment difficult. Bioelectrical impedance analysis is an alternative but the validity is unclear. The aim of this study was to determine the validity of bioelectrical impedance analysis for fluid measures in patients with septic shock.

Methods

Single-center, prospective observational cohort study. We included adult ICU patients with septic shock. We evaluated the agreement between measures on the left and right side of the patient and measures 1 h apart by two bioelectrical impedance devices. Results are presented as Bland Altman plots with 95% Limits of Agreements (LoA) and as correlations between bioelectrical impedance analysis results and clinical markers of fluids.

Results

Forty-nine patients were included. The agreement between measures on the left and the right side of the patient and after 1 h was overall without bias, but with wide LoA's. Fluid overload 1 h apart showed the most narrow 95% LoA (−2.4–2.9 L). The same wide limits of agreements were observed when comparing devices. For example, total body water with 95% LoA of −14.8 –16.7 L. Correlations between bioelectrical impedance analysis and clinical measures were low but statistically significant.

Conclusions

In patients with septic shock bioelectrical impedance analysis had no systematic errors or bias, but wide limits of agreement, indicating that the devices have a large and uncorrectable random error. Fluid status by bioelectrical impedance analysis is not sufficiently accurate to guide treatment in this group of patients.     

Role of the thymus and kidney graft in the maintenance of tolerance to heart grafts in miniature swine

BACKGROUND: The authors have examined the mechanism whereby co-transplantation of a kidney and heart from the same donor induces and maintains tolerance to both organs in miniature swine. METHODS: Transplants were performed across a major histocompatibility complex class I mismatch, and recipients received cyclosporine for 12 days. Group 1 animals received heart transplants alone (n=5), and all other groups received both heart and kidney allografts. Group 2 animals received no further intervention (n=2). Group 3 animals underwent transplant nephrectomy 8 days after heart and kidney co-transplantation (n=2). Group 4 animals underwent transplant nephrectomy 100 days after co-transplantation (n=2). Skin grafts were placed on group 4 animals, on one group 3 animal, and on two animals from group 2. Group 5 animals underwent thymectomy 100 days after co-transplantation (n=4). RESULTS: Group 1 animals developed cardiac allograft vasculopathy (CAV) and rejection. Group 2 animals never developed CAV and demonstrated in vitro donor-specific unresponsiveness. Group 3 animals suffered CAV and rejection. Group 4 animals developed CAV without concomitant donor-specific cell-mediated lympholysis reactivity, interstitial rejection, or cessation of graft function. Skin grafts on group 3 and group 4 animals led to fulminant rejection of heart and skin grafts, in contrast to grafts on group 2 animals that had no in vivo effect. Group 5 animals developed CAV but no significant increase in interstitial infiltrates. CONCLUSIONS: Both the kidney and thymus were necessary for maintenance of tolerance to heart allografts.     

Estimating the organ donor potential in Denmark: a prospective analysis of deaths in intensive care units in northern Denmark

To estimate the organ donor potential in Denmark we conducted a prospective registration of deaths in all intensive care units (ICUs), counting 15 ICUs and two neurosurgical ICUs in the four northern Danish counties, which cover a population of 1.64 million inhabitants or 30% of the Danish population. From September 1, 2000 till August 31, 2002, all deaths in the ICUs in 15 hospitals were recorded. Each case was evaluated locally postmortem with respect to medical suitability to organ donation. A total of 1655 deaths were recorded, corresponding to 504 deaths per million population per year (PMP). Median age was 70 years (0 to 99 years), 52% were more than 70 years, and 22% more than 80 years of age. The cause of death was cerebral lesion in 18% of the cases (neurosurgical ICUs: n = 182; ICUs: n = 110). By thorough medical record examination, the number of potential donors was estimated to be 169, corresponding to 51 PMP. The cause of death was cerebral lesion in 96% of the potential donors. Organ donation was performed in 43 cases (32 from neurosurgical ICUs and 11 from ICUs) or 13.1 PMP. Thus, 25% of the potential became organ donors. The major reason for nondonation was refusal from the relatives. Out of 127 questioned, the relatives refused in 62 cases (49%). By comparison, 74% of the general Danish population are willing to donate organs after death. The rate of nondetection of potential donors by the hospital staff could be estimated to 22%. In conclusion, the organ donor potential may allow for improvement in donation rates. An increased effort for donor hospitals is warranted. The motives for refusal by the relatives need elucidation.     

Attitudes, knowledge, and proficiency in relation to organ donation: a questionnaire-based analysis in donor hospitals in northern Denmark

The aim of this study was to assess knowledge, attitudes, and proficiency in relation to organ donation among staff members of intensive care units (ICUs) in donor hospitals, and possibly identify areas for improvement. The investigation was carried out as a collaboration between the transplant center and appointed key persons in all 17 ICUs in 15 hospitals in northern Denmark. A total of 1168 structured questionnaires were distributed to the health care professionals in the ICUs in the region; 689 were returned, giving a response rate of 59%. In general, there is a positive attitude among health care professionals toward organ donation. However, a considerable fraction of 11% declares to be against organ donation. Only 49% of the ICU health care professionals are willing to donate their own organs after death. By comparison, 74% of the general Danish population are willing to donate organs after death. Doctors are more positive toward organ donation than the nursing staff. Thus, 95% of the doctors are positive to organ donation compared to 81% of the nurses; 70% of the doctors will donate own organs after death compared to 45% of the nurses. Further, the survey demonstrates as expected a significant lack of experience in organ donation. Our data show a considerable need for more education and training, especially on how to inform and support the donor relatives and how to identify potential donors. The survey also discloses a substantial need for information regarding the results of transplantation.     

Evaluation of regional myocardial perfusion in patients with severe left ventricular dysfunction: Comparison of 13N-ammonia PET and 99mTc sestamibi SPECT

Objective

Positron emission tomography (PET) scanning with ¹³N-ammonia and ¹⁸FDG is well established for the detection of myocardial viability. Due to the limited availability of PET facilities, recent studies have combined technetium 99m sestamibi single photon emission computed tomography (SPECT) with ¹⁸FDG PET or ¹⁸FDG SPECT. This approach enables simultaneous assessment of regional myocardial blood flow and metabolism and substantially increases the capacity for viability detection. To validate whether ^99mTc-Sestamibi SPECT can replace ¹³N-ammonia PET, we compared these two modalities in patients with severe left ventricular dysfunction due to coronary artery disease.

Materials and Methods

Thirty-one patients (mean age 57±8 years; mean ejection fraction 27%±8%) with angiographically verified coronary artery disease were included. In random order, ammonia-PET and sestamibi-SPECT scans were performed. In a 20-segment model of the left ventricle, two blinded observers scored a total of 610 segments on a five-point scale. In a subset of 20 patients, 400 segments were scored twice to evaluate the observer variations of the two techniques. Segmental score differences were used to compare the imaging modalities. The impact on viability detection was assessed by combining the two flow tracers with FDG PET.

Results

Segmental comparison of the PET and SPECT studies yielded similar (difference ≤1) results in 74% of segments, reflecting regional concordance values in the lateral, apical, anterior, septal, and inferior myocardial walls of 86%, 82%, 71%, 66%, and 63%, respectively. The differences in the septal and inferior walls were primarily due to overestimation of perfusion defects by sestamibi SPECT, which yielded a higher proportion of mismatch patterns in those regions. The overall observer variations of the PET and SPECT studies were 7.5% and 5.8%.

Conclusion

Myocardial perfusion imaging with ¹³N-ammonia PET and ^99mTc-sestamibi SPECT yielded similar results in patients with severe left ventricular dysfunction, except for the septal and inferior regions. In these regions, SPECT tended to overestimate perfusion defects. Hence, attenuation correction should be considered when combining FDG PET and sestamibi SPECT for diagnosing myocardial viability to avoid overestimation of mismatch patterns in those regions.     

Gastrointestinal transit after laparoscopic versus open colonic resection

Background: Multimodal rehabilitation with epidural analgesia, early oral nutrition and mobilization, and laxative use has decreased the duration of ileus after colonic surgery to about 2 days, as compared with the usual 3 to 5 days of rehabilitation required after open surgery and the slightly shorter time required with laparoscopic surgery. Gastrointestinal transit after colonic resection with laparoscopy or laparotomy was assessed. Methods: In this study, 32 patients randomized to laparoscopic or open colonic resection received 4 MBq of ¹¹¹indium diethylenetriamine pentaacetic acid, a tracer, at the end of surgery. Images of the abdomen were obtained 24 and 48 h postoperatively. An opaque abdominal dressing blinded care personnel and patients to the procedure. Results: Defecation occurred on median day 2 postoperatively in both groups. At 48 h postoperatively, 53% of the tracer was excreted by patients in the laparoscopic group, as compared with 26% in the open group (p > 0.05). Conclusion: Postoperative ileus and gastrointestinal transit normalized within 48 h after colonic resection in the patients who received multimodal rehabilitation. No significant difference was observed between the patients who underwent the laparoscopic procedure and those who underwent the open procedure. Supported by Danish Pharmacy Foundation of 1991 and the Danish Research Council 9902757