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Rare neurological and neuropsychiatric manifestations of scrub typhus: a case series of 10 cases
No full text20.500.12530/87912Introduction: Scrub typhus is a potentially life-threatening but curable disease that can pro- duce multi-organ failure. Neurological manifestations in scrub typhus have gained attention recently, where the entire neural axis except the myoneural junction can be involved. Although the pathogenesis of neurological involvement has not been established, immune-mediated mechanisms are suspected. This article reports the clinicopathological features of scrub typhus cases presenting several rare neurological and neuropsychiatric manifestations. Methods: Three hundred fifty-four serologically confirmed scrub typhus cases were admitted to the Department of General Medicine of Burdwan Medical College and Hospital (West Ben- gal, India) between May 2018 and May 2022. There were 50 patients who had predominantly neurological manifestations. Of these 50 cases, ten patients presented with extremely rare neurological manifestations. Results: We report 10 cases of scrub typhus (four men and six women) who presented with com- plex neurological pictures (posterior reversible encephalopathy syndrome, Opalski syndrome, parkinsonism, cerebellitis, isolated opsoclonus, acute transverse myelitis, myositis, polyradicu- loneuropathy with cranial neuropathy, acute transient behavioral changes, and fibromyalgia). Immune-mediated mechanisms might have mediated the pathogenesis of most cases following scrub typhus infection.Conclusion: From a clinicopathological point of view, each case was unique in its presentation and treatment response. In any acute onset neurological disorders associated with febrile ill- ness in the tropics or subtropics, scrub typhus infection should be included in the differential diagnosis, despite the absence of eschar and unremarkable neuroimaging findings. This other- wise curable disease may result in multi-organ dysfunction syndrome and death if the diagnosis is delayed. (c) 2022 Published by Elsevier Espa & ntilde;a, S.L.U. on behalf of Sociedad Espa & ntilde;ola de Neurologia
Uncovering Surgical Dynamics and Trends in Early Breast Cancer Stage at Diagnosis: Key Insights From a Two-Decade Argentine Database Analysis.
No full textBreast cancer remains a major public health challenge worldwide, and understanding the trends and changes in breast cancer diagnosis and treatment over time is crucial for improving patient outcomes and guiding public health strategies. The Argentine Society of Mastology has maintained a comprehensive Breast Cancer Registry that provides valuable data for analyzing these trends. This retrospective analysis of the Breast Cancer Registry database evaluated changes in stages at the time of surgery, patterns of surgical care, and factors associated with higher stage diagnoses in patients with breast cancer in Argentina from January 2000 to December 2019. Overall, 13,239 patients met the inclusion criteria. Significant differences were observed in the axillary procedure performed, with sentinel lymph node biopsy increasing from 14.9% (2000-2004) to 69.5% (2015-2019; P Significant advances in the patterns of surgical care were identified. Numerous clinical and pathologic factors correlated with higher stage at diagnosis. However, multivariate analysis failed to show a noteworthy reduction in stage at diagnosis. This observation underscores the imperative to persistently strive to improve breast cancer care in Argentina
A phase I safety and efficacy clinical trial of plocabulin and gemcitabine in patients with advanced solid tumors.
No full textPlocabulin (Plo) induces depolymerization of tubulin fibers with disorganization and fragmentation of the microtubule network leading to mitosis. Plo combined with gemcitabine (Gem) showed synergistic anti-tumor activity in preclinical studies. This phase I trial evaluated the safety, pharmacokinetics (PK) and efficacy of Plo 10-min infusion plus Gem on Day 1 and 8 every 3-week in patients with advanced solid tumors. Fifty-seven patients were enrolled into 8 dose levels (DLs); 74%: females; 74%: ECOG performance status 1; median age: 62 years; median number of prior lines of therapy:3. Dose-limiting toxicities (DLT) in Cycle 1 were grade (G) 3 intestinal obstruction at the maximum tolerated dose (MTD), G3 peripheral sensory neuropathy (PSN), G3 abdominal pain, and G4 thrombocytopenia (1 patient each). The highest DL (DL8: Plo 10.5 mg/m2/Gem 1000 mg/m2) was the MTD. Accrual into DL7 (Plo 10.0 mg/m2/Gem 1000 mg/m2) was stopped before it was formally defined as the recommended dose (RD). Most common treatment-related adverse events (AEs) were fatigue (56%), nausea (55%), diarrhea (31%); G3/4 hematologic toxicities comprised anemia (35%), neutropenia (27%) and thrombocytopenia (17%). No treatment-related deaths occurred. PK parameters for Gem or dFdU at all DLs were in line with reference values from the literature. Six of 46 evaluable pts were responders (overall response rate:13%). Of note, 2 partial responses (PR) and 2 stable disease (SD) ≥ 4 months occurred among 13 pts with ovarian cancer. The combination of Plo and Gem is well tolerated. The MTD was Plo 10.5 mg/m2/Gem 1000 mg/m2. No PK drug-drug interaction was found. The most encouraging outcome occurred in ovarian cancer patients
Emergencia hipertensiva como debut de síndrome de Cushing paraneoplásico.
No full text20.500.12530/87909We present the case of a patient with a history of renal-vascular hypertension treated with stent one year previously, who attended the emergency room due to hypertensive emergency and dyspnea. Once the first suspicion of renal artery restenosis was ruled out with CT angiography, the study was completed, confirming the diagnosis of lung cancer through imaging and pathological anatomy. In the hormonal study, elevation of ACTH, hypercortisolism and analytical data of hyperaldosteronism were detected. With the final diagnosis of Cushing's syndrome secondary to ectopic production of ACTH, medical treatment was started, without being able to receive anything else due to the death of the patient after a few days
Metabolic and mitochondria alterations induced by SARS-CoV-2 accessory proteins ORF3a, ORF9b, ORF9c and ORF10.
No full text20.500.12530/87912Antiviral signaling, immune response and cell metabolism are dysregulated by SARS-CoV-2, the causative agent of COVID-19. Here, we show that SARS-CoV-2 accessory proteins ORF3a, ORF9b, ORF9c and ORF10 induce a significant mitochondrial and metabolic reprogramming in A549 lung epithelial cells. While ORF9b, ORF9c and ORF10 induced largely overlapping transcriptomes, ORF3a induced a distinct transcriptome, including the downregulation of numerous genes with critical roles in mitochondrial function and morphology. On the other hand, all four ORFs altered mitochondrial dynamics and function, but only ORF3a and ORF9c induced a marked alteration in mitochondrial cristae structure. Genome-Scale Metabolic Models identified both metabolic flux reprogramming features both shared across all accessory proteins and specific for each accessory protein. Notably, a downregulated amino acid metabolism was observed in ORF9b, ORF9c and ORF10, while an upregulated lipid metabolism was distinctly induced by ORF3a. These findings reveal metabolic dependencies and vulnerabilities prompted by SARS-CoV-2 accessory proteins that may be exploited to identify new targets for intervention
XVI Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2023 (II).
No full text20.500.12530/87897The XVI Post-ECTRIMS meeting was held in Seville on 20 and 21 October 2023, where expert neurologists in multiple sclerosis (MS) summarised the main new developments presented at the ECTRIMS 2023 congress, which took place in Milan from 11 to 13 October. The aim of this article is to summarise the content presented at the Post-ECTRIMS Meeting, in an article in two parts. This second part covers the health of women and elderly MS patients, new trends in the treatment of cognitive impairment, focusing particularly on meditation, neuroeducation and cognitive rehabilitation, and introduces the concept of fatigability, which has been used to a limited extent in MS. The key role of digitalization and artificial intelligence in the theoretically near future is subject to debate, along with the potential these technologies can offer. The most recent research on the various treatment algorithms and their efficacy and safety in the management of the disease is reviewed. Finally, the most relevant data for cladribine and evobrutinib are presented, as well as future therapeutic strategies currently being investigated
Reirradiation Practice in Gynecological Cancer: Insights from a National Survey in Spain.
No full text20.500.12530/87909Given the lack of standardisation in gynecological cancer reirradiation, the Gyneacologial Radiation Oncology (GINECOR) working group on behalf of the Spanish Society of Radiation Oncology (SEOR), works towards to inquire the current state of reirradiation practices among the radiation oncology departments in Spain. An online 37-question survey was sent to all GINECOR members, representing most Spanish centers. The survey addressed general aspects of reirradiation, including experience, reirradiation sites, and techniques used. It included seven clinical case scenarios on reirradiation, and a final section on technical aspects of external beam radiotherapy (EBRT) and brachytherapy (BT) treatment. Descriptive statistics were used for data analysis. Out of 58 centers, 29 responded, with 51.7% performing ≥ 5 reirradiation cases annually. While most centers offer multiple techniques, only 16/29 have access to BT. For in-field local relapse with surgery contraindicated, 79.3% performed BT in endometrial cancer, but only 27.5% treated with BT in cervical cancer recurrence. In this case, 17.2% used SBRT. For endometrial and cervical cancer, 44.8% and 65.4% of centers prescribed doses based on organ-at-risk tolerance, respectively. For pelvic wall/parametrial in-field relapse, 46.4% of the centres reirradiated with stereotactic body radiotherapy (SBRT), and 32.1% with BT. In nodal reirradiation, SBRT was preferred by 90% of centers. Variability was observed in target volume definitions for EBRT and proton therapy. Reirradiation for gynecological cancer remains unstandardized, presenting significant challenges in clinical practice. To improve reirradiation protocols in gynecological cancer, the GINECOR working group is currently conducting a systematic review and formulating Delphi recommendations
Comparison between tofacitinib and ustekinumab as a third-line therapy in refractory ulcerative colitis: A multicenter international study.
No full textUstekinumab and tofacitinib have recently been approved for the management of moderate to severe ulcerative colitis (UC). However, there is no evidence on how they should be positioned in the therapeutic algorithm. The aim of this study was to compare tofacitinib and ustekinumab as third-line therapies in UC patients in whom anti-TNF and vedolizumab had failed. This was a multicenter retrospective observational study. The primary outcome was disease progression, defined as the need for steroids, therapy escalation, UC-related hospitalization and/or surgery. Secondary outcomes were clinical remission, normalization of C-reactive protein, endoscopic remission, treatment withdrawal, and adverse events. One-hundred seventeen UC patients were included in the study and followed for a median time of 11.6 months (q1-q3, 5.5-18.7). Overall, 65% of patients were treated with tofacitinib and 35% with ustekinumab. In the entire study cohort, 63 patients (54%) had disease progression during the follow-up period. Treatment with ustekinumab predicted increased risk of disease progression compared to treatment with tofacitinib in Cox regression analysis (HR: 1.93 [95% CI: 1.06-3.50] p = 0.030). Twenty-eight (68%) patients in the ustekinumab group and 35 (46%) in the tofacitinib group had disease progression over the follow-up period (log-rank test, p Tofacitinib was more efficacious in reducing disease progression than ustekinumab in this cohort of refractory UC patients. However, prospective head-to-head clinical trials are needed as to confirm these data
Clustering COVID-19 ARDS patients through the first days of ICU admission. An analysis of the CIBERESUCICOVID Cohort.
No full text20.500.12530/87912Acute respiratory distress syndrome (ARDS) can be classified into sub-phenotypes according to different inflammatory/clinical status. Prognostic enrichment was achieved by grouping patients into hypoinflammatory or hyperinflammatory sub-phenotypes, even though the time of analysis may change the classification according to treatment response or disease evolution. We aimed to evaluate when patients can be clustered in more than 1 group, and how they may change the clustering of patients using data of baseline or day 3, and the prognosis of patients according to their evolution by changing or not the cluster. Multicenter, observational prospective, and retrospective study of patients admitted due to ARDS related to COVID-19 infection in Spain. Patients were grouped according to a clustering mixed-type data algorithm (k-prototypes) using continuous and categorical readily available variables at baseline and day 3. Of 6205 patients, 3743 (60%) were included in the study. According to silhouette analysis, patients were grouped in two clusters. At baseline, 1402 (37%) patients were included in cluster 1 and 2341(63%) in cluster 2. On day 3, 1557(42%) patients were included in cluster 1 and 2086 (57%) in cluster 2. The patients included in cluster 2 were older and more frequently hypertensive and had a higher prevalence of shock, organ dysfunction, inflammatory biomarkers, and worst respiratory indexes at both time points. The 90-day mortality was higher in cluster 2 at both clustering processes (43.8% [n = 1025] versus 27.3% [n = 383] at baseline, and 49% [n = 1023] versus 20.6% [n = 321] on day 3). Four hundred and fifty-eight (33%) patients clustered in the first group were clustered in the second group on day 3. In contrast, 638 (27%) patients clustered in the second group were clustered in the first group on day 3. During the first days, patients can be clustered into two groups and the process of clustering patients may change as they continue to evolve. This means that despite a vast majority of patients remaining in the same cluster, a minority reaching 33% of patients analyzed may be re-categorized into different clusters based on their progress. Such changes can significantly impact their prognosis