Hospital de Base

A síndrome de Sjogren é uma doença inflamatória autoimune crônica, caracterizada por comprometimento funcional das glândulas lacrimais e salivares. As manifestações clínicas são divididas em extraglandulares e glandulares exócrinas. A vasculite crioglonulinêmica, um exemplo de manifestação clínica extraglandular na doença de sjogren, desenvolve-se da deposição de imunocomplexos contendo crioglobulinas e quando presente, pode apresentar maior morbidade e mortalidade. A associação entre a síndrome de Sjogren primária e a vasculite crioglobulinêmica é rara e caso diagnosticada e tratada tardiamente pode apresentar possibilidade de progressão para desfechos desfavoráveis com importante impacto na qualidade de vida do paciente.

Plasmopara viticola, an obligate biotrophic oomycete, is the causal agent of downy mildew in grapevine (Vitis vinifera) and a major constraint to viticulture worldwide. Here, we report the first high-quality whole-genome assembly of an Indian P. viticola isolate (PV01), generated using a hybrid sequencing approach combining Illumina and Oxford Nanopore platforms. The assembled genome spans 84.09 Mb across 182 contigs, with an N50 of ~971 kb and 97% BUSCO completeness, and encodes 12,404 predicted protein-coding genes, diverse transposable elements, and lineage-specific expansions. Functional annotation revealed a rich repertoire of effectors, including RXLR, CRN, and apoplastic effectors, as well as putative virulence-associated and secretory proteins likely involved in host manipulation and immune suppression. Comparative ortholog analysis across P. viticola isolates and representative oomycetes identified a conserved core genome alongside 164 PV01-specific orthogroups, reflecting isolate-level diversification. Dual RNA-seq analysis of infected grapevine leaves revealed strong suppression of chloroplast- and photosynthesis-associated pathways in the host, coupled with induction of defense-related genes, including PR proteins, WRKY transcription factors, calcium signaling components, and JA/ET-mediated pathways. Concurrently, P. viticola displayed infection-stage–specific expression of effectors, apoplastic proteases, vesicle trafficking components, and genes associated with autophagy suppression and redox homeostasis. Together, these integrated genomic and transcriptomic analyses provide insights into the molecular mechanisms underlying P. viticola pathogenicity and grapevine immune modulation.

Human Papillomavirus (HPV) may be a predictive biomarker predictor for clinical outcome and influence treatment decisions in patients with Head and Neck Squamous Cell Carcinoma (HNSCC). We evaluated 253 patients with HNSCC from state of São Paulo, Brazil. The influence of p16INK4a expression was analyzed with epidemiological and clinical variables. In total, 32.4% of tumors studied had positive (+) p16INK4a protein expression, and 67.6% had negative. The variables were similar in both groups being the mostly with age under 64-years, male, white race, functional illiterate, smokers and alcoholics. The most affected primary site was oral cavity with T3/T4 tumoral stage, N1/N2/N3 nodals, M0 metastasis and III/IV clinical stage. Patients with oropharyngeal primary site and (+) p16INK4a, clinical staging III and chemotherapy treatment had worse survival. The median time of distant metastasis-free was 38.3-months in oropharyngeal (+) p16INK4a and 15.1-months in negative (-) p16INK4a. In the present study, the epidemiological variables are similar in both groups (Positive and negative p16INK4a expression): age under 64-years, male, white, functionally illiterate, smokers and alcoholics. There is no association of p16INK4a expression with primary site, however, the (-) p16INK4a shows better overall survival, higher frequencies in distant metastasis and less free time of the disease. Although the literature shows a greater survival in oropharynx (+) p16INK4a, our results are contradictory. It is suggested that future studies in different regions and with a larger sample size should be carried out to confirm these findings, because the patients who participated in the present study are only from a specific region of Brazil. 2B.

To compare the posterior keratometry (PK) values obtained with three instruments based on optical coherence tomography (Anterion [Heidelberg Engineering], IOLMaster 700 [Carl Zeiss Meditec AG], and MS-39 [CSO]), and one Scheimpflug camera biometer (Pentacam AXL Wave; Oculus Optikgeräte GmbH). The average keratometry (Kave), total corneal power (TCP), anterior-to-posterior ratio (A/P ratio), and posterior corneal astigmatism (PCA) were also compared. Measurements by the four instruments, expressed in diopters (D), were compared using repeated measures analysis of variance, when they were normally distributed, or Friedman's test, when they were not. One hundred eyes (100 consecutive patients) scheduled to undergo cataract surgery were prospectively enrolled. Statistically significant differences among the Anterion, IOLMaster 700, MS-39, and Pentacam AXL Wave were detected for PK: Anterion: -6.08 ± 0.23 D, IOLMaster 700: -5.77 ± 0.23 D, MS-39: -6.15 ± 0.26 D, and Pentacam AXL Wave: -6.26 ± 0.26 D (P < .0001); for Kave: Anterion: 43.19 ± 1.50 D, IOLMaster 700: 43.35 ± 1.49 D, MS-39: 43.36 ± 1.53 D, and Pentacam AXL Wave: 43.22 ± 1.55 D (P < .0001); for the A/P ratio: Anterion: 1.19 ± 0.02, IOLMaster 700: 1.12 ± 0.02, MS-39: 1.20 ± 0.03, Pentacam AXL Wave: 1.22 ± 0.03 (P < .0001); and for TCP: Anterion: 42.69 ± 1.51 D, IOLMaster 700: 43.36 ± 1.49 D, MS-39: 42.92 ± 1.52 D, and Pentacam AXL Wave: 42.35 ± 1.55 D (P < .0001). PCA revealed significant differences for the KP(45) and KP(0) vectors (P < .0001). The four instruments showed different PK values. The largest difference was observed with the IOL-Master 700, which provided the flattest PK and the lowest A/P ratio. The measurements cannot be considered interchangeable, and this should be considered when entering PK values into calculators using this parameter for IOL power.

PROpel (NCT03732820) demonstrated a statistically significant radiographic progression-free survival (rPFS) benefit with olaparib plus abiraterone (Ola + Abi) versus placebo plus abiraterone (P + Abi) in first-line metastatic castration-resistant prostate cancer (mCRPC). We conducted exploratory analyses in the intention-to-treat (ITT) population and subgroups stratified by homologous recombination repair gene mutation (HRRm) and BRCA1 and/or BRCA2 mutation (BRCAm) status. In PROpel, patients with mCRPC, without selection by HRRm status, were randomised 1:1 to first-line treatment with Ola (300mg twice daily; n=399) or P (n=397), each with Abi (1000mg daily) and prednisone/prednisolone (5mg twice daily). The primary endpoint was investigator-assessed rPFS. Exploratory endpoints were the objective response rate (ORR), duration of response (DoR), confirmed ≥50 decrease in prostate-specific antigen (PSA50-RR), and time to PSA progression; post hoc subgroup analyses by HRRm and BRCAm status were conducted. In the ITT population, the ORR was 58.4% with Ola + Abi versus 48.1% with P + Abi. The confirmed PSA50-RR was 79.3% with Ola + Abi and 69.2% with P + Abi. Median time to PSA progression in the ITT population was 24.2mo with Ola + Abi and 12.0mo with P + Abi (HR 0.59; 95% CI, 0.49-0.71). In the HRRm, no-HRRm, BRCAm, and no-BRCAm subgroups, results for ORR, DoR, confirmed PSA50-RR, and time to PSA progression favoured Ola + Abi, but these analyses were not powered for statistical significance. Results for ORR, DoR, confirmed PSA50-RR, and time to PSA progression favoured Ola + Abi over P + Abi in the ITT population and biomarker subgroups. The data support consideration of Ola + Abi as first-line treatment for mCRPC.