Tag: pubmed

Lancet. 2021 Mar 17:S0140-6736(21)00575-4. doi: 10.1016/S0140-6736(21)00575-4. Online ahead of print.

ABSTRACT

BACKGROUND: The degree to which infection with SARS-CoV-2 confers protection towards subsequent reinfection is not well described. In 2020, as part of Denmark’s extensive, free-of-charge PCR-testing strategy, approximately 4 million individuals (69% of the population) underwent 10·6 million tests. Using these national PCR-test data from 2020, we estimated protection towards repeat infection with SARS-CoV-2.

METHODS: In this population-level observational study, we collected individual-level data on patients who had been tested in Denmark in 2020 from the Danish Microbiology Database and analysed infection rates during the second surge of the COVID-19 epidemic, from Sept 1 to Dec 31, 2020, by comparison of infection rates between individuals with positive and negative PCR tests during the first surge (March to May, 2020). For the main analysis, we excluded people who tested positive for the first time between the two surges and those who died before the second surge. We did an alternative cohort analysis, in which we compared infection rates throughout the year between those with and without a previous confirmed infection at least 3 months earlier, irrespective of date. We also investigated whether differences were found by age group, sex, and time since infection in the alternative cohort analysis. We calculated rate ratios (RRs) adjusted for potential confounders and estimated protection against repeat infection as 1 – RR.

FINDINGS: During the first surge (ie, before June, 2020), 533 381 people were tested, of whom 11 727 (2·20%) were PCR positive, and 525 339 were eligible for follow-up in the second surge, of whom 11 068 (2·11%) had tested positive during the first surge. Among eligible PCR-positive individuals from the first surge of the epidemic, 72 (0·65% [95% CI 0·51-0·82]) tested positive again during the second surge compared with 16 819 (3·27% [3·22-3·32]) of 514 271 who tested negative during the first surge (adjusted RR 0·195 [95% CI 0·155-0·246]). Protection against repeat infection was 80·5% (95% CI 75·4-84·5). The alternative cohort analysis gave similar estimates (adjusted RR 0·212 [0·179-0·251], estimated protection 78·8% [74·9-82·1]). In the alternative cohort analysis, among those aged 65 years and older, observed protection against repeat infection was 47·1% (95% CI 24·7-62·8). We found no difference in estimated protection against repeat infection by sex (male 78·4% [72·1-83·2] vs female 79·1% [73·9-83·3]) or evidence of waning protection over time (3-6 months of follow-up 79·3% [74·4-83·3] vs ≥7 months of follow-up 77·7% [70·9-82·9]).

INTERPRETATION: Our findings could inform decisions on which groups should be vaccinated and advocate for vaccination of previously infected individuals because natural protection, especially among older people, cannot be relied on.

FUNDING: None.

PMID:33743221 | DOI:10.1016/S0140-6736(21)00575-4

Lancet Neurol. 2021 Apr;20(4):284-293. doi: 10.1016/S1474-4422(21)00001-6.

ABSTRACT

BACKGROUND: Spinal muscular atrophy type 1 is a motor neuron disorder resulting in death or the need for permanent ventilation by age 2 years. We aimed to evaluate the safety and efficacy of onasemnogene abeparvovec (previously known as AVXS-101), a gene therapy delivering the survival motor neuron gene (SMN), in symptomatic patients (identified through clinical examination) with infantile-onset spinal muscular atrophy.

METHODS: STR1VE was an open-label, single-arm, single-dose, phase 3 trial done at 12 hospitals and universities in the USA. Eligible patients had to be younger than 6 months and have spinal muscular atrophy with biallelic SMN1 mutations (deletion or point mutations) and one or two copies of SMN2. Patients received a one-time intravenous infusion of onasemnogene abeparvovec (1·1 × 10¹⁴ vector genomes per kg) for 30-60 min. During the outpatient follow-up, patients were assessed once per week, beginning at day 7 post-infusion for 4 weeks and then once per month until the end of the study (age 18 months or early termination). Coprimary efficacy outcomes were independent sitting for 30 s or longer (Bayley-III item 26) at the 18 month of age study visit and survival (absence of death or permanent ventilation) at age 14 months. Safety was assessed through evaluation of adverse events, concomitant medication usage, physical examinations, vital sign assessments, cardiac assessments, and laboratory evaluation. Primary efficacy endpoints for the intention-to-treat population were compared with untreated infants aged 6 months or younger (n=23) with spinal muscular atrophy type 1 (biallelic deletion of SMN1 and two copies of SMN2) from the Pediatric Neuromuscular Clinical Research (PNCR) dataset. This trial is registered with ClinicalTrials.gov, NCT03306277 (completed).

FINDINGS: From Oct 24, 2017, to Nov 12, 2019, 22 patients with spinal muscular atrophy type 1 were eligible and received onasemnogene abeparvovec. 13 (59%, 97·5% CI 36-100) of 22 patients achieved functional independent sitting for 30 s or longer at the 18 month of age study visit (vs 0 of 23 patients in the untreated PNCR cohort; p<0·0001). 20 patients (91%, 79-100]) survived free from permanent ventilation at age 14 months (vs 6 [26%], 8-44; p<0·0001 in the untreated PNCR cohort). All patients who received onasemnogene abeparvovec had at least one adverse event (most common was pyrexia). The most frequently reported serious adverse events were bronchiolitis, pneumonia, respiratory distress, and respiratory syncytial virus bronchiolitis. Three serious adverse events were related or possibly related to the treatment (two patients had elevated hepatic aminotransferases, and one had hydrocephalus).

INTERPRETATION: Results from this multicentre trial build on findings from the phase 1 START study by showing safety and efficacy of commercial grade onasemnogene abeparvovec. Onasemnogene abeparvovec showed statistical superiority and clinically meaningful responses when compared with observations from the PNCR natural history cohort. The favourable benefit-risk profile shown in this study supports the use of onasemnogene abeparvovec for treatment of symptomatic patients with genetic or clinical characteristics predictive of infantile-onset spinal muscular atrophy type 1.

FUNDING: Novartis Gene Therapies.

PMID:33743238 | DOI:10.1016/S1474-4422(21)00001-6

Jpn J Radiol. 2021 Mar 20. doi: 10.1007/s11604-021-01110-y. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the diagnostic performance of ultrafast and standard dynamic contrast-enhanced (DCE)-MRI in evaluating the residual disease after neoadjuvant chemotherapy (NAC) for breast cancer.

MATERIALS AND METHODS: Sixty-seven consecutive patients underwent MRI after NAC. Visual analysis of enhancement was performed on ultrafast and standard DCE-MRI, and compared between no residual disease and residual disease groups. The lesion diameters measured on the last phase of ultrafast DCE-MRI and early and delayed phases of standard DCE-MRI were compared with pathological diameter of entire residual cancer and residual invasive ductal carcinoma (IDC).

RESULTS: The visual analysis in the delayed phase of standard DCE-MRI exhibited the highest sensitivity (90%), whereas ultrafast DCE-MRI revealed the highest positive predictive value (92%). There were no significant differences between the diameters in the delayed phase of the standard DCE-MRI and the pathological entire residual cancer (p = 0.97), and the diameters in ultrafast DCE-MRI and the pathological residual IDC (p = 0.97).

CONCLUSION: The delayed phase of standard DCE-MRI may be effective for detecting the residual disease and evaluating the extension of entire residual cancer. Enhancement in ultrafast DCE-MRI may be strongly suggestive of the presence of residual disease, and effective for evaluating the extension of residual IDC.

PMID:33743147 | DOI:10.1007/s11604-021-01110-y

Jpn J Radiol. 2021 Mar 20. doi: 10.1007/s11604-021-01107-7. Online ahead of print.

ABSTRACT

BACKGROUND: Multiple prominent hypointense vessels on susceptibility-weighted image (SWI) have been found in the ischemic territory of patients with acute ischemic stroke. SWI is suitable for venous imaging.

PURPOSE: To evaluate the conditions of prominent hypointense vessel (PHV) in hyperacute and acute cerebral infarctions using susceptibility-weighted image (SWI).

MATERIALS AND METHODS: Magnetic resonance images, including SWI, of 284 patients with acute infarction were evaluated. Based on lesion size, the infarction was classified as a small (< 3 cm) or a large (> 3 cm) infarction. Stage of infarction was classified as hyperacute (< 6 h) or acute (> 6 h, < 1 week) on the basis of the onset of stroke. The site of infarction was categorised as a deep grey matter or a mixed (cortical and/or deep grey matter) infarction. The venous structures were analysed qualitatively for the calibre difference between ipsilateral and contralateral hemispheres. We quantitatively analysed the relationship between the size of areas with PHV on SWI and the abnormalities on MR angiography, apparent diffusion coefficient value, and signal intensity on T2WI in the 271 patients.

RESULTS: PHV over the infarction site was observed in 54.1% (137/253) of the large infarctions, and 19.3% (6/31) of the small infarctions on SWI. PHV was demonstrated in 63.1% (118/187) of mixed infarctions and 25.8% (25/97) of deep grey matter infarctions, and 59.2% (58/98) in hyperacute and 45.7% (85/186) of acute infarctions. The presence of PHV was statistically significant in the size and region of cerebral infarction (p < 0.05), and was not significant in the stage of infarction (p = 0.137). Quantitative analysis revealed significant differences in the MRA abnormalities and ADC values in the PHV ( +) group (p < 0.05) and no significant difference in the T2WI SI ratio in the PHV ( +) group (p = 0.086), compared with PHV (-) group.

CONCLUSION: PHV on SWI was more prominent at the portions with the large and mixed infarctions. PHV was observed both in hyperacute and acute infarction.

PMID:33743148 | DOI:10.1007/s11604-021-01107-7

Hum Cell. 2021 Mar 20. doi: 10.1007/s13577-021-00520-4. Online ahead of print.

ABSTRACT

The polymorphism rs2853669 in the telomerase reverse transcriptase gene (TERT) promoter region is widely investigated for the risk of different cancers. However, previous results remained inconclusive. Thus, we performed this updated meta-analysis to comprehensively evaluate the association between rs2853669 and the susceptibility of human cancer. A systematic literature search via PubMed, EMBASE, Cochrane Library, and Web of Science databases was conducted that produced a total of 19 eligible studies containing 23,085 subjects. The relationship was calculated with the odds ratio (OR) and 95% confidence intervals (CIs). Statistical analyses were performed using the RevMan 5.4 software. The analysis indicated that rs2853669 is associated with an enhanced risk of overall cancer risk. From subgroup analysis, a significantly increased association in five genetic models (p < 0.05) was found among Asians, but no association was observed in Caucasians. Although we did not find any significant correlation between rs2853669 and breast cancer, an increased and statistically significant association was found for both lung cancer and acute myeloid leukemia. We did not find any association in other cancer types during stratified analysis. Our meta-analysis suggests that rs2853669 polymorphism in TERT gene is associated with an increased risk of overall cancer susceptibility, particularly in the Asian population. Moreover, rs2853669 is significantly associated with lung cancer and acute myeloid lymphoma. However, large-scale studies are needed to confirm our findings.

PMID:33743166 | DOI:10.1007/s13577-021-00520-4

Hernia. 2021 Mar 20. doi: 10.1007/s10029-021-02392-x. Online ahead of print.

ABSTRACT

PURPOSE: The primary goal of this study was to determine the incidence of occult paraumbilical hernias during open primary umbilical hernia repair. The secondary objective was to further characterize the clinical features of these patients and hernias.

METHODS: This was a retrospective chart review of patients undergoing primary umbilical hernia repair at Shouldice Hospital, from 2007 to 2017. Inclusion criteria were utilized to elucidate patients, where a concomitant occult paraumbilical hernia was found. Descriptive statistics were used throughout.

RESULTS: 5850 patients underwent primary umbilical hernia repair, 459 (7.85%) patients had concomitant primary umbilical and paraumbilical hernias. There was a preoperative suspicion/diagnosis of a paraumbilical hernia in 166 (2.8%) of these patients. In 293 (5.01%) patients who had open primary umbilical hernia repair, at least one associated occult paraumbilical defect was found during surgery. Most of umbilical and concomitant occult paraumbilical hernias were small and medium size defects. The great majority of the reported occult paraumbilical hernias were found in the supraumbilical position at a distance of 3 cm or less from the top of the umbilical defect.

CONCLUSION: The incidence of concomitant occult paraumbilical hernias in patients mildly overweight undergoing primary umbilical hernia repair is 5.01%, relevant to surgical decision-making. Since the great majority of these paraumbilical defects are superior to the umbilical defect, an adequate incision and dissection for at least 3 cm above the umbilical hernia may reduce the number of missed concomitant hernias and result in less presumed recurrences.

PMID:33743094 | DOI:10.1007/s10029-021-02392-x

Doc Ophthalmol. 2021 Mar 20. doi: 10.1007/s10633-021-09827-x. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the validity of electrophysiological tests in the early diagnosis of a ganglion cells and/or optic nerve dysfunction in patients with pituitary microadenoma.

METHODS: 66 eyes, from 33 patients with microadenoma with no evidence of the optic chiasm compression in magnetic resonance imaging (MRI) and the visual impairment in the routine ophthalmological examination, standard static perimetry (24-2 white on white) and optical coherence tomography (HD-OCT), were analysed. The pattern electroretinogram (PERG), standard pattern visual evoked potentials (PVEPs) and multichannel visual evoked potentials (mVEPs) (ISCEV standards) were performed. The results obtained from the electrophysiological tests were compared to the same number of age-matched healthy controls.

RESULTS: Statistically significant differences between the patients with microadenoma and healthy controls were detected in all electrophysiological tests (p < 0.001). The most frequent abnormalities were observed in mVEPs (25/33 patients, 75.8%; 43/66 eyes, 65.2%). The most frequent features registered in this test were: (1°4′)-an increase in the P100wave latency from uncrossed fibres (13/33 patients, 39.39%; 21/66 eyes, 31.8%) and (0°16′)-an amplitude reduction of this wave from the crossed fibres (11/33 patients, 33.33%; 19/66 eyes, 28.8%). The changes in PVEPs (15/33 patients, 45.5%; 25/66 eyes, 37.9%) and PERG (10/33 patients, 30.3%; 15/66 eyes, 22.7%) were also registered. Of all the tests and parameters analysed in the study, the greatest diagnostic value in detecting the visual pathway dysfunction in this group of patients was the amplitude of P100 wave from the crossed fibres of the mVEPs (1°4′) with a sensitivity of 60.6% and a specificity of 93.8%. These parameters suggest that this type of dysfunction is downstream to the chiasm and can also indicate the visual pathway dysfunction severity.

CONCLUSIONS: In patients with microadenoma, the abnormalities in the electrophysiological tests are registered even without clinical evidence of visual impairment from the routine ophthalmological examination, SAP, OCT and chiasmal compression in MRI. The mVEPs have the most significant role in the diagnosis of the visual pathway dysfunction in patients with microadenoma.

PMID:33743105 | DOI:10.1007/s10633-021-09827-x

J Robot Surg. 2021 Mar 20. doi: 10.1007/s11701-021-01227-2. Online ahead of print.

ABSTRACT

Robotic-assisted laparoscopic surgery attempts to facilitate rectal surgery in the narrow space of the pelvis. The aim of this study is to compare the outcomes of robotic versus laparoscopic surgery for rectal cancer. Monocentric retrospective study including 300 patients who underwent robotic (n = 178) or laparoscopic (n = 122) resection between Jan 2009 and Dec 2017 for high, mid and low rectal cancer. The robotic and laparoscopic groups were comparable with regard to pretreatment characteristics, except for sex and ASA status. There were no statistical differences between groups in the conversion rate to open surgery. Surgical morbidity and oncological quality did not differ in either group, except for the anastomosis leakage rate and the affected distal resection margin. There were no differences in overall survival rate between the laparoscopic and robotic group. Robotic surgery could provide some advantages over conventional laparoscopic surgery, such as three-dimensional views, articulated instruments, lower fatigue, lower conversion rate to open surgery, shorter hospital stays and lower urinary and sexual dysfunctions. On the other hand, robotic surgery usually implies longer operation times and higher costs. As shown in the ROLARR trial, no statistical differences in conversion rate were found between the groups in our study. When performed by experienced surgeons, robotic surgery for rectal cancer could be a safe and feasible option with no significant differences in terms of oncological outcomes in comparison to laparoscopic surgery.

PMID:33743145 | DOI:10.1007/s11701-021-01227-2

Heart Vessels. 2021 Mar 20. doi: 10.1007/s00380-021-01836-9. Online ahead of print.

ABSTRACT

BACKGROUND: The Japanese high-bleeding-risk criteria (Japanese-HBR), modified criteria of the Academic Research Consortium (ARC) HBR, has been recently proposed. We aimed to investigate the prevalence of the ARC-HBR and the Japanese-HBR, and to assess their prognostic significance in patients with acute myocardial infarction (AMI).

METHODS AND RESULTS: We applied the ARC-HBR and the Japanese-HBR criteria to the OACIS prospective multicenter acute myocardial infarction registry (12,093 patients, 66 ± 12 years, 9,096 males). The primary endpoint was fatal bleeding (BARC-5). Median follow-up duration was 4.84 [inter-quartile range 1.35, 5.01] years. Prevalence of the ARC-HBR was 43.8%, while that of the Japanese-HBR was 61.8%. Cumulative incidence of fatal bleeding was higher in the ARC-HBR group than in the no ARC-HBR group at 1 year (1.3 vs. 0.6%) and at 5 years (2.0 vs. 0.7%). The Kaplan-Meier curves stratified by the Japanese-HBR criteria more prominently diverged (1.3 vs. 0.2% at 1 year; and 1.9 vs. 0.3% at 5 years). The Japanese-HBR criteria showed superior discriminative performance over the ARC-HBR criteria (C-statistics: 0.677 vs. 0.598, P < 0.001).

CONCLUSIONS: In the real-world Japanese AMI registry, nearly half of the patients fulfilled the criteria of ARC-HBR, and two-thirds met the Japanese-HBR. Our findings support the validity of both ARC- and Japanese-HBR criteria in AMI patients but encourage the future application of the Japanese-HBR criteria to the Japanese AMI cohort.

TRIAL REGISTRATION NUMBER: UMIN000004575.

PMID:33743047 | DOI:10.1007/s00380-021-01836-9

World J Urol. 2021 Mar 20. doi: 10.1007/s00345-021-03661-1. Online ahead of print.

ABSTRACT

PURPOSE: To examine the ability of the Decipher test to predict early biochemical recurrence after radical prostatectomy and to impact clinical decisions in advance of metastasis and death.

METHODS: We identified Decipher tests ordered after radical prostatectomy for adverse pathology in men treated for prostate cancer between 1/1/14 and 8/31/18. Biochemical recurrence was defined as prostate-specific antigen > 0.02 ng/mL. Decipher score is reported as lower risk (< 0.6) and higher risk ≥ 0.60). Kaplan-Meier analysis was used to examine the relationship between Decipher score and time to biochemical recurrence (months). Cox regression was used to analyze the relationship between Decipher score and time to biochemical recurrence while controlling for a number of clinical characteristics. Secondary analyses focused on a subset of men with prostate-specific antigen > 0.02 and < 0.20 ng/mL to determine if high-risk Decipher scores were associated with receipt of salvage treatment.

RESULTS: A total of 203 cases were analyzed: 37.9% and 62.1% had lower and higher risk Decipher scores respectively, and 56.2% had a biochemical recurrence. Median (inter-quartile range) follow-up was 20 (13.5, 25.3) months. Decipher score was significantly associated with time to biochemical recurrence (p = 0.027) while in the secondary analyses, high-risk Decipher scores (≥ 0.60) were associated with salvage treatment (p = 0.018). Stage category and Decipher score were significant predictors of time from elevated PSA to salvage treatment in the secondary analyses.

CONCLUSION: While it might not contribute statistically, Decipher score can be clinically useful in helping patients reach treatment decisions.

PMID:33743058 | DOI:10.1007/s00345-021-03661-1