Background Old age is one of the most important risk factors for severe COVID-19. Few studies have analyzed changes in the clinical characteristics and prognosis of COVID-19 among older adults before ...the availability of vaccines. This work analyzes differences in clinical features and mortality in unvaccinated very old adults during the first and successive COVID-19 waves in Spain. Methods This nationwide, multicenter, retrospective cohort study analyzes unvaccinated patients greater than or equai to 80 years hospitalized for COVID-19 in 150 Spanish hospitals (SEMI-COVID-19 Registry). Patients were classified according to whether they were admitted in the first wave (March 1-June 30, 2020) or successive waves (July 1-December 31, 2020). The endpoint was all-cause in-hospital mortality, expressed as the case fatality rate (CFR). Results Of the 21,461 patients hospitalized with COVID-19, 5,953 (27.7%) were greater than or equai to 80 years (mean age IQR: 85.6 82.3-89.2 years). Of them, 4,545 (76.3%) were admitted during the first wave and 1,408 (23.7%) during successive waves. Patients hospitalized in successive waves were older, had a greater Charlson Comorbidity Index and dependency, less cough and fever, and met fewer severity criteria at admission (qSOFA index, PO2/FiO2 ratio, inflammatory parameters). Significant differences were observed in treatments used in the first (greater use of antimalarials, lopinavir, and macrolides) and successive waves (greater use of corticosteroids, tocilizumab and remdesivir). In-hospital complications, especially acute respiratory distress syndrome and pneumonia, were less frequent in patients hospitalized in successive waves, except for heart failure. The CFR was significantly higher in the first wave (44.1% vs. 33.3%; -10.8%; p < 0.001) and was higher among patients greater than or equai to 95 years (54.4% vs. 38.5%; -15.9%; p < 0.001). After adjustments to the model, the probability of death was 33% lower in successive waves (OR: 0.67; 95% CI: 0.57-0.79). Conclusions Mortality declined significantly between the first and successive waves in very old unvaccinated patients hospitalized with COVID-19 in Spain. This decline could be explained by a greater availability of hospital resources and more effective treatments as the pandemic progressed, although other factors such as changes in SARS-CoV-2 virulence cannot be ruled out. Keywords: COVID-19, SARS-CoV-2, Aged, 80 and over, Comorbidity, Morbidity, Mortality, Complications, Epidemiology, Spain
We present an Aboriginal Australian genomic sequence obtained from a 100-year-old lock of hair donated by an Aboriginal man from southern Western Australia in the early 20th century. We detect no ...evidence of European admixture and estimate contamination levels to be below 0.5%. We show that Aboriginal Australians are descendants of an early human dispersal into eastern Asia, possibly 62,000 to 75,000 years ago. This dispersal is separate from the one that gave rise to modern Asians 25,000 to 38,000 years ago. We also find evidence of gene flow between populations of the two dispersal waves prior to the divergence of Native Americans from modern Asian ancestors. Our findings support the hypothesis that present-day Aboriginal Australians descend from the earliest humans to occupy Australia, likely representing one of the oldest continuous populations outside Africa.
Very little information is available on the mutational landscape of vulvar squamous cell carcinoma (VSCC), a disease that mainly affects older women. Studies focusing on the mutational patterns of ...the currently recognized etiopathogenic types of this tumor human papillomavirus (HPV)-associated (HPV-A), HPV-independent (HPV-I) with TP53 mutation (HPV-I/TP53mut), and HPV-I with wild-type TP53 (HPV-I/TP53wt) are particularly rare, and there is almost no information on the prognostic implications of these abnormalities.
Whole-exome DNA sequencing of 60 VSCC and matched normal tissues from each patient was performed. HPV detection, immunohistochemistry (IHC) for p16, p53, and mismatch repair proteins were also performed.
Ten tumors (16.7%) were classified as HPV-A, 37 (61.7%) as HPV-I/TP53mut, and 13 (21.6%) as HPV-I/TP53wt. TP53 was the most frequently mutated gene (66.7%), followed by FAT1 (28.3%), CDKN2A (25.0%), RNF213 (23.3%), NFE2L2 (20%) and PIK3CA (20%). All the 60 tumors (100%) were DNA mismatch repair proficient. Seventeen tumors (28.3%) showed CCND1 gain. Bivariate analysis, adjusted for FIGO stage, revealed that TP53 mutation, CCND1 gain, and the combination of the two alterations were strongly associated with impaired recurrence-free survival (hazard ratio=4.4, p<0.001) and disease-specific survival (hazard ratio=6.1, p=0.002). Similar results were obtained when p53 IHC status was used instead of TP53 status and when considering only HPV-I VSCC. However, in the latter category, p53 IHC maintained its prognostic impact only in combination with CCND1 gains. All tumors carried at least one potentially actionable genomic alteration.
In conclusion, VSCCs with CCND1 gain represent a prognostically adverse category among HPV-I/TP53mut tumors. All patients with VSCCs are potential candidates for targeted therapy.
Background: The major limitation of piecemeal endoscopic mucosal resection (EMR) is the inaccurate histological assessment of the resected specimen, especially in cases of submucosal invasion. ...Objective: To classify non-pedunculated lesions ≥20 mm based on endoscopic morphological features, in order to identify those that present intramucosal neoplasia (includes low-grade neoplasia and high-grade neoplasia) and are suitable for piecemeal EMR. Design: A post-hoc analysis from an observational prospective multicentre study conducted by 58 endoscopists at 17 academic and community hospitals was performed. Unbiased conditional inference trees (CTREE) were fitted to analyse the association between intramucosal neoplasia and the lesions’ endoscopic characteristics. Result: 542 lesions from 517 patients were included in the analysis. Intramucosal neoplasia was present in 484 of 542 (89.3%) lesions. A conditional inference tree including all lesions’ characteristics assessed with white light imaging and narrow-band imaging (NBI) found that ulceration, pseudodepressed type and sessile morphology changed the accuracy for predicting intramucosal neoplasia. In ulcerated lesions, the probability of intramucosal neoplasia was 25% (95%CI: 8.3–52.6%; p < 0.001). In non-ulcerated lesions, its probability in lateral spreading lesions (LST) non-granular (NG) pseudodepressed-type lesions rose to 64.0% (95%CI: 42.6–81.3%; p < 0.001). Sessile morphology also raised the probability of intramucosal neoplasia to 86.3% (95%CI: 80.2–90.7%; p < 0.001). In the remaining 319 (58.9%) non-ulcerated lesions that were of the LST-granular (G) homogeneous type, LST-G nodular-mixed type, and LST-NG flat elevated morphology, the probability of intramucosal neoplasia was 96.2% (95%CI: 93.5–97.8%; p < 0.001). Conclusion: Non-ulcerated LST-G type and LST-NG flat elevated lesions are the most common non-pedunculated lesions ≥20 mm and are associated with a high probability of intramucosal neoplasia. This means that they are good candidates for piecemeal EMR. In the remaining lesions, further diagnostic techniques like magnification or diagnostic +/− therapeutic endoscopic submucosal dissection should be considered.
We describe the feasibility of monitoring with a Textile Wearable Holter (TWH) in patients included in Crypto AF registry.
We monitored cryptogenic stroke patients from stroke onset (<3days) ...continuously during 28days. We employed a TWH composed by a garment and a recorder. We compared two garments (Lead and Vest) to assess rate of undiagnosed Atrial Fibrillation (AF) detection, monitoring compliance, comfortability (1 to 5 points), skin lesions, and time analyzed. We describe the timing of AF detection in three periods (0–3, 4–15 and 16–28days).
The rate of undiagnosed AF detection with TWH was 21.9% (32 out of 146 patients who completed the monitoring). Global time compliance was 90% of the time expected (583/644h). The level of comfortability was 4 points (IQR 3–5). We detected reversible skin lesions in 5.47% (8/146). The comfortability was similar but time compliance (in hours) was longer in Vest group 591 (IQR 521–639) vs. Lead 566 (IQR 397–620) (p=0.025). Also, time analyzed was more prolonged in Vest group 497 (IQR 419–557) vs. Lead (336h (IQR 140–520) (p=0.001)). The incidence of AF increases from 5.6% (at 3days) to 17.5% (at 15th day) and up to 20.9% (at 28th day). The percentage of AF episodes detected only in each period was 12.5% (0–3days); 21.7% (4–15days) and 19% (16–28days).
28days Holter monitoring from the acute phase of the stroke was feasible with TWH. Following our protocol, only five patients were needed to screen to detected one case of AF.
We present an Aboriginal Australian genomic sequence obtained from a 100-year-old lock of hair donated by an Aboriginal man from southern Western Australia in the early 20th century. We detect no ...evidence of European admixture and estimate contamination levels to be below 0.5%. We show that Aboriginal Australians are descendants of an early human dispersal into eastern Asia, possibly 62,000 to 75,000 years ago. This dispersal is separate from the one that gave rise to modern Asians 25,000 to 38,000 years ago. We also find evidence of gene flow between populations of the two dispersal waves prior to the divergence of Native Americans from modern Asian ancestors. Our findings support the hypothesis that present-day Aboriginal Australians descend from the earliest humans to occupy Australia, likely representing one of the oldest continuous populations outside Africa.
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