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Background: Mechanisms triggering the pathogenesis of chronic spontaneous urticaria (CSU) have been identified as type I autoallergic (which is associated with IgE antibodies against autoantigens) and type IIb autoimmune (which is driven by autoantibodies to FceR1 and/or IgE). Objective: Our aim was to define presumptive endotypes in patients with CSU by using tests amenable to use in routine clinical practice. Methods: A retrospective analysis of the medical records of 394 patients with CSU with or without chronic inducible urticaria or angioedema was performed. Patients were assigned to 1 of 4 groups as follows: (1) type I endotype of CSU, if they presented at least 1 of the following: allergic disease, total IgE level of at least 40UI/mL, and positive result of skin tests to inhalant allergen(s), (2) type IIb endotype of CSU, if they presented at least 1 of following: autoimmune disease, low total IgE level less than 40 IU/mL, positive autologous serum skin test result, positive for antinuclear antibodies in a titer of at least 1:160, and elevated level of anti–thyroid peroxidase, (3) overlap of type I/type IIb endotypes of CSU, if they presented with at least 1 marker of both type I and type IIb, and (4) non–type I/type IIb endotype of CSU, if they presented with none of the markers of type I or type IIb. Results: The mean age at onset of symptoms was 34 years; 82.2% of those with CSU were female, and angioedema and chronic inducible urticaria were found in 74.8% and 31.9% of patients, respectively. Of the patients with CSU, 38% presented with the type I endotype and 51% presented with type I/type IIb overlap, whereas 9% presented with the type IIb endotype and 2% presented with the non–type I/type IIb endotype. Eosinopenia was associated with type IIb and type I/type IIb overlap as opposed to the type I and non–type I/type IIb endotypes (P = .02). Conclusions: Most patients with CSU presented with features of the type 1 (autoallergic) endotype, whether associated with type IIb (autoimmune) endotype or not.

Background:. The long-term outcome of mandible reconstruction when performed in children has not been well documented. Methods:. This is a retrospective case series of patients who underwent immediate oncologic mandible reconstruction with a fibula free flap at younger than 18 years of age over a 20-year period, by a single surgeon, who had long-term follow-up. Results:. A total of 10 patients met inclusion criteria. Patient age ranged from 3 years and 8 months to 17 years and 9 months (mean 11 years). The etiology was malignant tumors in seven patients and benign locally aggressive tumors in three patients. All fibula flaps survived. All donor sites were closed primarily. The mean follow-up duration was 10 years and 5 months (range 3–20 years). The mean patient age at follow-up was 21 years and 10 months (range 8 years and 9 months to 30 years and 9 months). All patients achieved a regular diet and normal speech. Final occlusion was normal in seven of 10 patients. The aesthetic outcome, as evaluated by clinical examination, was a symmetric mandible in eight patients (in the other two the aesthetic asymmetry and malocclusion was minor and did not require operative intervention). Dental implants were ultimately placed in three patients. Leg function was normal in eight patients. Achilles lengthening and tendon transfer was required in one patient, and one patient developed ankle pain associated with running. Conclusion:. Mandible reconstruction in children with the fibula free flap provides excellent aesthetic and functional outcomes that are durable over time.

Neurological manifestations of COVID-19 may affect both central and peripheral nervous systems. Unlike in adults, in whom majority of severe cases derive from respiratory complications, neurological involvement is one of the main causes of severe COVID-19 in children. This study aimed to detect viral respiratory pathogens, mainly SARS-CoV-2, in nasopharynx and cerebrospinal fluid samples utilizing qRT-PCR (TaqMan) in a pediatric population in Brazil. We evaluated four children with neurological symptoms and laboratory-confirmed SARS-CoV-2 infection: three presenting with meningoencephalitis and one presenting with Guillain-Barré syndrome. All four patients had mild respiratory symptoms. SARS-CoV-2 RNA was identified in two cerebrospinal fluid samples. SARS-CoV-2 involvement should be considered for differential diagnosis in pediatric cases presenting neurological alterations even if symptoms such as headache, anosmia, or dizziness are absent.

Summary:. Management of radial forearm donor sites following free flap reconstruction of head and neck tumor defects typically requires split-thickness skin grafting. Tendon exposure and delayed healing are occasional problems associated with skin grafting over the distal forearm musculature. Others have reported the use of negative pressure wound therapy (NPWT) devices to bolster split-thickness grafts and improve graft take. Although this approach works well, these devices are not always approved by third-party payers for outpatient use, requiring patients to remain in the hospital or have these devices removed before discharge. The authors report outcomes using a miniaturized NPWT device to bolster the skin graft on radial forearm free flap donor sites in 10 consecutive patients compared with 10 consecutive control patients managed with traditional bolster dressings. The 2 groups of patients were similar in terms of demographics, indication for reconstruction, and size of donor site. There was less skin graft loss and a lower rate of tendon exposure and infection in the miniaturized NPWT device group, though these results did not reach statistical significance. Recently developed miniaturized, single-use NPWT devices can be reliably used as bolsters for skin grafts with some notable advantages over reusable NPWT devices.

Summary:. The appropriate reconstruction of an infrastructure maxillectomy defect requires vascularized bone for maxillary arch restoration, soft tissue bulk for filling the residual defect extending up to the orbital floor, and a thin tissue layer for resurfacing the palate and adjacent cheek mucosa. Although several free tissue flaps have been previously described as reconstructive options, each possesses limitations. We describe the fibula osteofascial flap with flexor hallucis longus muscle, no skin paddle, and a “gullwing” fascial component, as an ideal reconstructive option for these specific maxillary defects. It satisfies the necessary requirements of bone, restoration of intraoral surfaces, as well as additional soft tissue volume to provide the optimal aesthetic and functional result. It also has the added benefit of minimizing morbidity to, and improving aesthetics of, the donor site. This is demonstrated through a case presentation and review of the existing literature.

Benign prostatic hyperplasia (BPH) affects up to 80% of men by age 80, with large-gland BPH often treated by simple prostatectomy (SP). This technique significantly improves symptoms but is associated with high rates of complications such as transfusions and infections. Minimally invasive techniques, including robotic-assisted laparoscopic simple suprapubic prostatectomy (RALSP), have emerged as alternatives. This study reports on 162 patients who underwent RALSP from May 2018 to June 2023. The mean age of the patients was 69 years, mean prostate volume 144.8 cm 3 , mean robot time 78.7 min, and mean blood loss 183.1 mL. Results demonstrated significant improvements in the results: prostate volume (mean decrease from 144.8 to 26.6 cm 3 ), mean PSA level decreased from 7.8 to 0.8 (p < 0.0001), mean IPSS decreased from 23.0 to 4.4 (p < 0.0001), and mean uroflowmetry increased from 6.3 to 22.6 ml/s (p < 0.0001). No patient experienced worsening erectile function after surgery. All patients showed absence of stress urinary incontinence within 3 months. Catheterization time decreased from 4.2 to 2.6 days over the study period. The postoperative complication rate was 2.29%, with no need for surgical reintervention for complications. While RALSP showed promising results, further prospective studies are needed to compare it with other techniques. This study highlights RALSP as a viable minimally invasive option for treating large-volume BPH, offering reduced recovery times and fewer complications., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Introduction: Neoadjuvant cisplatin-based combination chemotherapy (NAC) followed by radical cystectomy is the standard of care for cisplatin-fit patients harboring muscle-invasive bladder cancer (MIBC). Prediction of response to NAC is essential for clinical decision-making regarding alternatives in case of non-response, and bladder-sparing in case of complete response. This research aimed to assess the performance of machine learning in predicting therapeutic response following NAC treatment in patients with MIBC., Methods: A systematic review adhering to the PRISMA guidelines was conducted until July 2023. The study integrated articles relating to artificial intelligence and NAC response in MIBC from various databases. The quality of articles was evaluated using the Quality Assessment Tool for Diagnostic Accuracy Studies 2 (QUADAS-2). A meta-analysis was subsequently performed on selected studies to determine the sensitivity and specificity of machine learning algorithms in predicting NAC response., Results: Of 655 articles identified, 12 studies comprising 1523 patients were included, and four studies were eligible for meta-analysis. The sensitivity and specificity of the studies were 0.62 (95% confidence interval [CI] 0.50-0.72) and 0.82 (95% CI 0.72-0.89), respectively, with a heterogeneity score (I 2 ) of 38.5%. The machine learning algorithms used computed tomography, genetic, and anatomopathologic data as input and exhibited promising potential for predicting NAC response., Conclusions: Machine-learning algorithms, especially those using computed tomography, genetic, and pathologic data, demonstrate significant potential for predicting NAC response in MIBC. Standardization of methodologic data analysis and response criteria are needed as validation studies.

Competing Interests: Disclosure The authors declare no conflicts of interest.

Purpose: Limited high-quality studies have compared robot-assisted laparoscopic prostatectomy (RALP) vs open retropubic radical prostatectomy. We sought to compare their postoperative outcomes in a randomized setting., Materials and Methods: In a single center, 354 men with newly diagnosed prostate cancer were assessed for eligibility; 342 were randomized (1:1). The primary outcome was 90-day complication rates. Functional outcomes and quality of life were assessed over 18 months, and oncological outcomes, biochemical recurrence-free survival, and additional treatment over 36 months., Results: From 2014 to 18, 327 patients underwent surgery (retropubic radical prostatectomy = 156, RALP = 171). Complications occurred in 27 (17.3%) vs 19 (11.1%; P = .107). Patients undergoing RALP experienced lower median bleeding (250.0 vs 719.5 mL; P < .001) and shorter hospitalization time. Urinary EPIC (Expanded Prostate Cancer Index Composite) median scores were better for RALP over 18 months, with higher continence rate at 3 months (80.5% vs 64.7%; P = .002), 6 months (90.1% vs 81.6%; P = .036) and 18 months (95.4% vs 78.8%; P < .001). Sexual EPIC and Sexual Health Inventory for Men median scores were higher with RALP up to 12 months, while the potency rate was superior at 3 months (23.9% vs 5.3%; P = .001) and 6 months (30.6% vs 6.9%; P < .001). Quality of life over the 18 months and oncological outcomes over 36 months were not significantly different between arms., Conclusions: Complications at 90 days were similar. RALP showed superior sexual outcomes at 1 year, improved urinary outcomes at 18 months, and comparable oncological outcomes at 36 months., Trial Registration: Prospective Analysis of Robot-Assisted Surgery; NCT02292914. https://clinicaltrials.gov/ct2/show/NCT02292914?cond=NCT02292914&draw=2&rank=1.

Objective: To provide an updated view on the role of cell-free DNA as a predictor of pathological response to neoadjuvant therapy in patients with muscle-invasive bladder cancer., Methods: A systematic review was conducted from September 2023 to October 2023. Selected studies from the MEDLINE and clinical trial databases were critically analyzed regarding the clinical efficacy of cell-free DNA as a predictive instrument after neoadjuvant therapy in bladder cancer. The methodological quality assessment was based on the QUADAS-2 tool., Results: In this systematic review, we analyzed 5 studies encompassing a cumulative patient cohort of 780 individuals diagnosed with muscle-invasive bladder cancer, with a median follow-up ranging from 6 to 23 months. Among these studies, 4 primarily focused on detecting and analyzing circulating tumor DNA in plasma, while 1 study uniquely utilized cell-free tumor DNA in urine samples. The diagnostic accuracy of cell-free DNA in plasma ranges from 79% to 100%, indicating a variable yet significant predictive capability. In contrast, the study utilizing urinary cell-free DNA demonstrated an accuracy of 81% in predicting treatment response post-neoadjuvant chemotherapy., Conclusion: Cell-free DNA is emerging as a valuable biomarker for predicting response to neoadjuvant chemotherapy in patients with muscle-invasive bladder tumors., Competing Interests: Disclosure The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Here, in a multi-ancestry genome-wide association study meta-analysis of kidney cancer (29,020 cases and 835,670 controls), we identified 63 susceptibility regions (50 novel) containing 108 independent risk loci. In analyses stratified by subtype, 52 regions (78 loci) were associated with clear cell renal cell carcinoma (RCC) and 6 regions (7 loci) with papillary RCC. Notably, we report a variant common in African ancestry individuals ( rs7629500 ) in the 3' untranslated region of VHL, nearly tripling clear cell RCC risk (odds ratio 2.72, 95% confidence interval 2.23-3.30). In cis-expression quantitative trait locus analyses, 48 variants from 34 regions point toward 83 candidate genes. Enrichment of hypoxia-inducible factor-binding sites underscores the importance of hypoxia-related mechanisms in kidney cancer. Our results advance understanding of the genetic architecture of kidney cancer, provide clues for functional investigation and enable generation of a validated polygenic risk score with an estimated area under the curve of 0.65 (0.74 including risk factors) among European ancestry individuals., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Objective: To validate the Cancer of the Bladder Risk Assessment (COBRA) score in patients with urothelial variants., Methods: Epidemiological, clinical, radiological, and anatomopathological data were collected from patients with urothelial carcinoma who underwent radical cystectomy at the Institute of Cancer of São Paulo between May 2008 and December 2022. Patients with the presence of at least 10% of any urothelial variants in the radical cystectomy specimens' anatomopathological exam were included in the study. The COBRA score and derivatives were applied and correlated with oncological outcomes., Results: A total of 680 patients [482 men (70.9%) and 198 women (29.1%)]; 66 years (IQR 59-73) underwent radical cystectomy for bladder tumor, and of these patients, a total of 167 patients presented any type of urothelial variant. The median follow-up time was 28.77 months (IQR 12-85). The three most prevalent UV were squamous differentiation (50.8%), glandular differentiation (31.3%), and micropapillary differentiation (11.3%). The subtypes with the worst prognosis were sarcomatoid with a median survival of 8 months (HR 1.161; 95% CI 0.555-2.432) and plasmacytoid with 14 months (HR 1.466; 95% CI 0.528-4.070). The COBRA score for patients with micropapillary variants demonstrated good predictive accuracy for OS (log-rank P = 0.009; 95% IC 6.78-29.21) and CSS (log-rank P = 0.002; 95% IC 13.06-26.93)., Conclusions: In our study, the COBRA score proved an effective risk stratification tool for urothelial histological variants, especially for the micropapillary urothelial variant. It may be helpful in the prognosis evaluation of UV patients after radical cystectomy., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Surgical intervention is the treatment of choice in patients with urachal carcinoma. Due to complications and to reduce hospital stay from open surgery, minimally invasive approaches are desirable. Nowadays, robotic-assisted surgery has become increasingly popular, and robot-assisted cystectomy can be performed in patients with urachal carcinoma with low complication rates., Methods: We performed a systematic review to search for studies that evaluated patients who underwent robotic-assisted surgery for urachal carcinoma. The outcomes of interest were the type of cystectomy performed, whether there was umbilicus resection, total operative time, console time, intraoperative complications, estimated blood loss, postoperative complications, time of hospitalisation, positive surgical margins and the presence of documented tumour recurrence., Results: In this study, we evaluated three cohorts comprising a total of 21 patients. The median follow-up period ranged from 8 to 40 months. Medium age was between 51 and 54 years, with a majority (63.1%) being male. One patient (5.2%) underwent a radical cystectomy, and 19 patients (94.7%) underwent to partial cystectomy. Umbilical resections were performed in all cases, and pelvic lymphadenectomy in 14 cases (73.6%). Recurrence occurred in three patients at a median of 17 months postoperation, two cases in the trocar insertion site. Additionally, there was one death, which was attributed to postoperative cardiovascular complications., Conclusion: Robotic-assisted partial cystectomy has a low incidence of adverse outcomes in patients with urachal carcinoma. Controlled studies, ideally randomised, are warranted to establish the comparative efficacy and safety of the robotic-assisted cystectomy approach relative to open surgery., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Authors. BJUI Compass published by John Wiley & Sons Ltd on behalf of BJU International Company.)

Objective: We aim to create a new score to predict postoperative overall survival in patients with nonmetastatic T3aN0 renal cell carcinoma., Methods: We reviewed the clinical data of adult patients who underwent radical nephrectomy for renal cell carcinoma between December 2007 and January 2022 in a single tertiary oncological institution. Clinical characteristics, clinical-pathological staging and histopathological characteristics were analysed. Survival analyses were determined using the Kaplan-Meier curve. A nomogram was established using Cox proportional hazard regression to identify the prognostic factors affecting the overall survival. The area under the curve, calibration curves and decision curve analysis were used to evaluate prognostic efficacy., Results: We analyzed 362 patients classified as pT3aN0M0 stage with a median follow-up of 40 months. According to Cox univariate and multivariate analyses, weight loss greater than 5% in 6 months before surgery, stage V chronic kidney disease after radical nephrectomy, sarcomatoid pattern, and coagulative tumor necrosis were identified as predictors of overall survival. We developed a score and performed internal and external validation. The time-dependent receiver operating characteristic curve, area under the curve value and calibration curve analysis showed good prediction ability of the score. The nomogram can effectively predict and stratify overall survival after radical nephrectomy in patients with pT3aN0M0 renal cell carcinoma., Conclusion: Patients with pT3aN0MO renal cell carcinoma exhibited different characteristics, and those with unfavourable characteristics deserve greater attention during follow-up. This nomogram provides an accurate prediction of overall survival after radical nephrectomy., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Authors. BJUI Compass published by John Wiley & Sons Ltd on behalf of BJU International Company.)

Human contact with wild animals in synanthropic habits is often mediated by arthropod vectors such as ticks. This is an important method of spreading infectious agents that pose a risk to human health. Thus, this study aimed to molecularly detect Ehrlichia spp., Anaplasma spp., Borrelia spp., and protozoa of the order Piroplasmida in ticks collected from coatis of Iguaçu National Park (PNI), Paraná, Brazil. This study involved 553 ticks DNA, including Amblyomma spp. larvae, Haemaphysalis juxtakochi nymphs, Amblyomma brasiliense, Amblyomma coelebs, and adults of Amblyomma ovale. The DNA extracted from each sample was subjected to polymerase chain reaction (PCR) targeting the genes 23S rRNA for the Anaplasmataceae family, 16S rRNA for Anaplasma spp., dsb for Ehrlichia spp., flaB, 16S rRNA, hpt, and glpQ for Borrelia spp., and 18S rRNA for Piroplasmid protozoans. DNA from Anaplasma sp. was detected in ticks of the species A. coelebs (4/553); Borrelia sp. DNA was detected in A. coelebs (3/553), A. ovale (1/553), and Amblyomma larvae (1/553); and Theileria sp. was detected in A. coelebs (2/553). All tested samples were negative for Ehrlichia spp. Our study constitutes the newest report in South America of these microorganisms, which remain poorly studied., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The present study aimed to describe the occurrence of Borrelia spp. in cattle in the states of Minas Gerais and Pará in southeastern and northern Brazil, respectively. Bovine whole blood samples were examined by blood smear and polymerase chain reaction (PCR) to detect the flagellin B (flaB) gene of Borrelia spp. Frequencies of positive animals for Borrelia spp. were 1.52% (2/132) in the municipality of Unaí, Minas Gerais, and 14.2% (2/7) in the municipality of Marabá, Pará. Subsequent genetic sequencing confirmed that the detected spirochetes close to the species B. theileri. In both locations, the animals positive for B. theileri were also highly infested by Rhipicephalus microplus ticks. Despite the low frequency of Borrelia spp., the occurrence of this spirochete indicates that further studies are needed to determine the consequences in cattle herds., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

The in vitro feeding of ticks facilitates the conduction of studies involving the intrinsic vector-pathogen relationship, susceptibility tests, and resistance to acaricides, in addition to mimicking the use of experimental hosts. The objective of this study was to establish an in vitro feeding system using silicone membranes to supply various diets to the species Ornithodoros rostratus. Each experimental group included 130 first-instar O. rostratus nymphs. The groups were divided according to the diet provided: citrated rabbit blood, citrated bovine blood, bovine blood with antibiotics, and defibrinated bovine blood. The control group was fed directly on rabbits. Ticks were weighed before and after the feeding and monitored individually according to their biological parameters. The results of the experiment demonstrated that the proposed system was efficient in terms of fixation stimulus and satisfactory in terms of tick engorgement, which would allow the maintenance of O. rostratus colonies by using artificial feeding through silicone membranes. All diets provided were efficient for the maintenance of colonies, but the ticks that received citrated rabbit blood displayed similar biological parameters to those observed under in vivo feeding conditions., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Recent studies about intense neoadjuvant therapy followed by Radical Prostatectomy (RP) lack standardized criteria regarding surgical complications and comparison to a group of patients who underwent RP without the use of neoadjuvant therapy. The aim of this study is to describe and compare the perioperative complication rates., Materials and Methods: This was a prospective, single-center phase II trial in patients with high-risk prostate cancer (HRPCa). The control group included HRPCa patients who underwent RP outside the clinical trial during the same study recruitment period. The interventional group was randomized (1:1) to receive neoadjuvant androgen deprivation therapy plus abiraterone with or without apalutamide followed by RP. Complications observed up to 30 days of surgery were classified based on the Clavien-Dindo classification. Uni- and multivariate analyses were carried out to assess predictive factors associated with perioperative complications., Results: In total, 124 patients with HRPCa were underwent to RP between May 27, 2019 and August 6, 2021, including 61 patients in the intervention group and 63 patients in the control group. The general and major complications in the intervention group reached 29.6% and 6.6%, respectively, and 39.7% and 7.9% in the control group, respectively. There was no significant difference between groups. We observed 4.9% of thromboembolic event in the neoadjuvant group., Conclusions: There was no significant increase in morbidity rate in RP after intense neoadjuvant therapy. The association of intense androgen deprivation neoadjuvant therapy with RP and extended pelvic lymphadenectomy may increase the risk of a perioperative thromboembolic events., (Copyright © 2022 Elsevier Inc. All rights reserved.)

This study evaluates the presence of bacterial and protozoan agents in ticks and fleas found on wild animals in the state of Rio de Janeiro, Brazil. These ectoparasites were collected on mammal species Hydrochoerus hydrochaeris, Tapirus terrestris, Dicotyles tajacu, Didelphis aurita, Cuniculus paca, Cerdocyon thous, and Coendou prehensilis, and on the terrestrial bird Dromaius novaehollandiae. Ticks and fleas were identified morphologically using specific taxonomic keys. A total of 396 ticks and 54 fleas were tested via polymerase chain reaction (PCR) for the presence of Rickettsia spp., Borrelia spp., microorganisms of the order Piroplasmida and Anaplasmataceae family. This total is distributed among nine tick species of the genus Amblyomma and one flea species. Rickettsia bellii was detected in Amblyomma dubitatum and Amblyomma pacae; Rickettsia sp. strain AL was found in Amblyomma longirostre; Rickettsia parkeri strain Atlantic rainforest was found in Amblyomma ovale; and "Candidatus Rickettsia senegalensis" and Rickettsia felis were detected in Ctenocephalides felis felis. Wolbachia sp. was detected in C. f. felis, and Borrelia sp. was detected in Amblyomma calcaratum (here named Borrelia sp. strain Acalc110). All tested samples were negative for Ehrlichia spp. and microorganisms of the Piroplasmida order. This study detected a new bacterial strain, Borrelia sp. strain Acalc 110 (which is genetically close to B. miyamotoi and B. venezuelensis) and the Rickettsia sp. strain 19P, which is 100% similar to "Ca. R. senegalensis", a bacterium recently discovered and now being reported for the first time in Brazil., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier GmbH.)

Background: Canine monocytic ehrlichiosis (CME) is caused by the tick-borne pathogen Ehrlichia canis, an obligate intracellular Gram-negative bacterium of the family Anaplasmataceae with tropism for canine monocytes and macrophages. The trp36 gene, which encodes for the major immunoreactive protein TRP36 in E. canis, has been successfully used to characterize the genetic diversity of this pathogen in different regions of the world. Based on trp36 sequence analysis, four E. canis genogroups, United States (US), Taiwan (TWN), Brazil (BR) and Costa Rica (CR), have been identified. The aim of this study was to characterize the genetic diversity of E. canis in Cuba based on the trp36 gene., Methods: Whole blood samples (n = 8) were collected from dogs found to be infested with the tick vector Rhipicephalus sanguineus sensu lato (s.l.) and/or presenting clinical signs and symptoms of CME. Total DNA was extracted from the blood samples and trp36 fragments were amplified by PCR. Nucleotide and protein sequences were compared using alignments and phylogenetic analysis., Results: Four of the trp36 sequences obtained (n = 8) fall within the phylogenetic cluster grouping the US genogroup E. canis strains. The other E. canis trp36 sequences formed a separate and well-supported clade (94% bootstrap value) that is phylogenetically distant from the other major groups and thus represents a new genogroup, herein designated as the 'Cuba (CUB) genogroup'. Notably, dogs infected with the CUB genogroup presented frequent hemorrhagic lesions., Conclusions: The results of this study suggest that genetic diversification of E. canis in Cuba is associated with the emergence of E. canis strains with increased virulence., (© 2022. The Author(s).)

Purpose: Partial nephrectomy is the standard treatment for renal tumors <7 cm, and the trend toward minimally invasive surgery has increased. However, data that could support its use and benefits are still lacking., Materials and Methods: We conducted a prospective, randomized controlled trial comparing surgical, functional and oncologic outcomes in patients undergoing open partial nephrectomy (OPN) or laparoscopic partial nephrectomy (LPN). Randomization was 1:1 to OPN or LPN for the treatment of renal tumors <7 cm. The primary endpoint was surgical complications up to 90 days after surgery. Secondary outcomes were comparison of surgical, oncologic and functional results., Results: We randomized 208 patients between 2012 and 2020 (110 with OPN vs 98 with LPN). Operative data showed no differences in operative time, warm ischemia time, estimated blood loss, transfusions or length of hospital stay. Zero ischemia was more frequent in the OPN (35.4% vs 15.5%, p=0.02). OPN was associated with more abdominal wall complications (31.2% vs 13.1%, p=0.004). Regarding oncologic outcomes, no differences were noted. The LPN group had less kidney function reduction at 3 (-5.2% vs -10%, p=0.04; CI 0.09 to 9.46) and 12 months after surgery (-0.8% vs -6.3%, p=0.02; CI 1.18 to 12.95), and a lower rate of downstaging on the chronic kidney disease classification at 12 months (14.1% vs 32.6%, p=0.006)., Conclusions: Surgical and oncologic outcomes of LPN were similar to OPN. Minimally invasive surgery may provide better preservation of kidney function. More studies, especially those involving robotic surgery, are necessary to confirm our findings.

Penile cancer (PeC) is a rare disease, and no prognostic biomarkers have been adopted in clinical practice yet. The objective of the present study was to identify differentially expressed miRNAs (DEmiRs) and genes (DEGs) as potential biomarkers for lymph node metastasis and other prognostic factors in PeC. Tumor samples were prospectively obtained from 24 patients with squamous cell carcinoma of the penis. miRNA microarray analysis was performed comparing tumors from patients with inguinal lymph node metastatic and localized disease, and the results were validated by qRT-PCR. Eighty-three gene expression levels were also compared between groups through qRT-PCR. Moreover, DEmiRs and DEGs expression levels were correlated with clinicopathological variables, cancer-specific (CSS), and overall survival (OS). TAC software, TM4 MeV 4.9 software, SPSS v.25.0, and R software v.4.0.2 were used for statistical analyses. We identified 21 DEmiRs in microarray analysis, and seven were selected for validation. miR-744-5p and miR-421 were overexpressed in tissue samples of metastatic patients, and high expression of miR-421 was also associated with lower OS. We found seven DEGs ( CCND1 , EGFR , ENTPD5 , HOXA10 , IGF1R , MYC , and SNAI2 ) related to metastatic disease. A significant association was found between increased MMP1 expression and tumor size, grade, pathological T stage, and perineural invasion. Other genes were also associated with clinicopathological variables, CSS and OS. Finally, we found changes in mRNA-miRNA regulation that contribute to understanding the mechanisms involved in tumor progression. Therefore, we identified miRNA and mRNA expression profiles as potential biomarkers associated with lymph node metastasis and prognosis in PeC, in addition to disruption in mRNA-miRNA regulation during disease progression.

Objective: The coronavirus disease 2019 (COVID-19) pandemic has had a major impact globally. While sleep problems have increased during the pandemic, their impact on specific populations is less well known. The objective of this study was to measure the impact of the COVID-19 pandemic on sleep and how it correlates with the feeling of isolation in individuals aged ≥ 50 years., Methods: A cross-sectional study was conducted using data from the Survey of Health, Aging, and Retirement conducted between June and August 2020. A multivariate logistic regression model was performed to analyze the outcome "more or less trouble sleeping since the outbreak" and its main predictors., Results: The mean ± SD age of the participants was 71 ± 9 years. Since the outbreak, 29% reported a deterioration of their quality of sleep. Being male and older were found to be significant predictors of more sleep complaints (OR = 1.13; P  = .004; CI, 1.04-1.23 and OR = 1.02; P  = .000; CI, 1.02-1.03, respectively). Moreover, those who claimed that they often felt alone or more loneliness since the beginning of the outbreak also had more trouble sleeping (OR = 1.21; P  = .002; CI, 1.07-1.37 and OR = 4.06; P  = .000; CI, 2.75-5.99, respectively)., Conclusions: Male sex, older age, and loneliness are associated with more sleeping difficulties since the beginning of the COVID-19 pandemic. These findings can aid health authorities to address sleep issues in this vulnerable population more directly., (© Copyright 2022 Physicians Postgraduate Press, Inc.)

Tick-borne pathogens belong to one of the two main groups of occupational biohazards, and occupational exposure to such agents puts soldiers at risk of zoonotic infections, such as those caused by rickettsiae. There are few studies on acarological fauna and occupational risk in military areas in Brazil. Thus, the present study aimed to analyze the diversity of ticks present in the military training areas of municipalities in the Southeast Region of Brazil. The ticks were collected from the selected areas using the dragging and flagging techniques as well as by visual detection on the operators' clothing, and environmental information was also recorded. A total of ten species were collected from the 66 surveyed areas, belonging to five genera and nine species: Amblyomma sculptum, Amblyomma dubitatum, Amblyomma brasiliense, Amblyomma longirostre, Amblyomma aureolatum, Dermacentor nitens, Rhipicephalus spp., Ixodes spp. and Haemaphysalis spp. The frequent presence of tick species in military training areas along with traces and sightings of wild animals, most commonly capybaras (Hydrochoerus hydrochaeris), in most of the studied areas, indicates high levels of exposure of the military to tick vectors of spotted fever group rickettsiae and the possible occurrence of infections among the troops.

Dogs are important in the epidemiology of tick-borne diseases, playing a significant role mainly in endemic areas of rickettsiosis and borreliosis, and serving as sentinels in epidemiological surveys. We analyzed the distribution of Rickettsia and Borrelia spp. in dogs and their ticks in the municipalities of Guaxupé, Minas Gerais, and Tapiratiba, São Paulo, Brazil, two areas non-endemic for Baggio-Yoshinari Syndrome (BYS) and rickettsiosis. Serum from 242 dogs of different ages (>12 months) and breeds were tested by the Indirect Immunofluorescence Assay (IFA) using specific antigens for Rickettsia rickettsii, Rickettsia parkeri, Rickettsia amblyommatis, Rickettsia rhipicephali, and Rickettsia bellii, and by an indirect Enzyme Linked Immunosorbent Assay (ELISA) for the detection of homologous IgG antibodies against Borrelia burgdorferi American strain G39/40. Ticks were collected from the animals and subjected to PCR and nested PCR for detection of Rickettsia spp. (synthase citrate gene) and Borrelia spp. (flagellin gene). Serological data showed that 7.85% (19/242) of the analyzed dogs were seropositive for at least one of the five Rickettsia antigens tested; one (0.41%) was considered seropositive for R. parkeri (1:64) and one (0.41%) for R. rickettsii (1:256). Nine (3.72%) were considered seropositive for R. bellii and one (0.41%) for R. amblyommatis; a seroprevalence of 13.64% (33/242) for IgG class immunoreactive antibodies against B. burgdorferi was observed. A total of 148 ticks were collected from the dogs; among these 3.40% were identified as larvae of the genus Rhipicephalus and 0.70% of the genus Amblyomma; 89.8% were identified as Rhipicephalus sanguineus, 4.70% Amblyomma sculptum and 1.40% Amblyomma ovale; all negative for PCR of Rickettsia spp. and nested PCR for Borrelia spp.. The serological findings of this study suggest the circulation of Rickettsiae associated with the spotted fever group and vector ticks, just like Borrelia spp. in a non-endemic Brazilian area, drawing attention to the possibility of a zoonotic cycle in the region., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: To evaluate the association of neutrophil-to-lymphocyte ratio (NLR) with recurrence-free survival (RFS) and overall survival (OS) in patients with locally advanced nonmetastatic clear cell renal cell carcinoma (ccRCC) undergoing radical nephrectomy., Material and Methods: We retrospectively identified 880 nephrectomies performed between January 2009 and December 2016 in a single center, reviewed data from 478 radical nephrectomies for kidney tumors and identified 187 patients with locally advanced nonmetastatic ccRCC (pT3-T4 N0M0). NLR was obtained preoperatively and calculated by dividing absolute neutrophil count by absolute lymphocyte count. OS and RFS were evaluated by the Kaplan-Meier method. Cox proportional-hazards regression models were used to evaluate predictors of RFS and OS., Results: Among 187 patients with ccRCC (mean age 63.4 ± 11.5 years; 118 [63.1%] male), the median follow-up was 48.7 months. On univariate analysis, in patients with Fuhrman nuclear grade of differentiation 3-4, the median time to recurrence was significantly shorter with NLR ≥ 4 than < 4 (24 vs. 55 months, P = .045). On multivariable analysis adjusted for NLR ≥ 4, among all variables analyzed (NLR, microvascular invasion, sarcomatoid differentiation, tumor size and body mass index), only nuclear grade of differentiation was an independent predictor of recurrence (hazard ratio 2.18; 95% confidence interval 1.07-4.92, P = .03). The 3-year OS had no statistically significant difference between patients with NLR ≥ 4 or < 4., Conclusion: For patients with locally advanced, nonmetastatic ccRCC, RFS was reduced with high nuclear grade of differentiation and high preoperative NLR. These findings suggest an association between higher NLR and worse outcomes in locally advanced ccRCC., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Wild animals are of considerable importance in the ecology of infectious agents, as they can function as hosts and even as possible vectors. In this study, DNA from Rickettsia spp. was detected on ticks and fragments of skin collected from wild coatis with synanthropic habits in the Iguaçu National Park (INP) in the state of Paraná in southern Brazil. Testing was carried out on a total of 566 ticks, comprising Amblyomma spp. larvae, nymphs of Haemaphysalis juxtakochi, Amblyomma brasiliense, Amblyomma coelebs, and adults of Amblyomma ovale. The samples were tested by polymerase chain reaction (PCR) by amplifying htrA, gltA, ompA, and ompB gene fragments to detect Rickettsia spp. A fragment of each positive sample was sequenced in both directions, submitted to Genbank for a homology search, and also used for phylogenetic analyses. Samples of A. coelebs (1.90%, 8/420), A. ovale (13%, 6/45), and ring-tailed coati skin (1%, 1/75) amplified Rickettsia spp. DNA. Through sequencing, Rickettsia bellii was observed in A. ovale, Rickettsia amblyommatis in A. coelebs, while Rickettsia rhipicephali was detected in the skin samples. Wild ring-tailed coatis with synanthropic habits in the INP and their ticks are infected by Rickettsia spp., and associations with new hosts have been described., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

Clear cell renal cell carcinoma (ccRCC) has been considered a metabolic disease, with loss of von Hippel-Lindau (VHL) gene and consequent overexpression of hypoxia-inducible factor 1 alpha (HIF-1α), which is central for tumor development and progression. Among other effects, HIF-1α is involved in the metabolic reprogramming of cancer cells towards the Warburg effect involved in tumor cell proliferation, migration and survival. In this context, several proteins are expressed by cancer cells, including glucose and lactate transporters as well as different pH regulators. Among them, monocarboxylate transporters (MCTs) can be highlighted. Our aim is to comprehensively analyze the immunoexpression of MCT1, MCT2, MCT4, CD147, CD44, HIF-1α, GLUT1 and CAIX in ccRCC surgical specimens correlating with classical prognostic factors and survival of patients with long follow-up. Surgical specimens from 207 patients with ccRCC who underwent radical or partial nephrectomy were used to build a tissue microarray. Immunostaining was categorized into absent/weak or moderate/strong and related to all classic ccRCC prognostic parameters. Kaplan-Meier curves were generated to assess overall and cancer-specific survival, and multivariate analysis was performed to identify independent prognostic factors of survival. Multivariate analysis showed that MCT1 together with tumor size and TNM staging, were independently related to cancer-specific survival. MCT1, CD147, CD44 and GLUT1 expression were significantly associated with poor prognostic factors. We show that MCT1 is an independent prognostic factor for cancer-specific survival in ccRCC justifying the use of new target therapies already being tested in clinical trials., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Penile cancer (PeC) carcinogenesis is not fully understood, and no biomarkers are reported in clinical practice. We aimed to investigate molecular signatures based on miRNA and mRNA and perform an integrative analysis to identify molecular drivers and pathways for PeC development. Affymetrix miRNA microarray was used to identify differentially expressed miRNAs (DEmiRs) comparing 11 tumoral tissues (TT) paired with non-neoplastic tissues (NNT) with further validation in an independent cohort ( n = 13). We also investigated the mRNA expression of 83 genes in the total sample. Experimentally validated targets of DEmiRs, miRNA-mRNA networks, and enriched pathways were evaluated in silico. Eight out of 69 DEmiRs identified by microarray analysis were validated by qRT-PCR (miR-145-5p, miR-432-5p, miR-487b-3p, miR-30a-5p, miR-200a-5p, miR-224-5p, miR-31-3p and miR-31-5p). Furthermore, 37 differentially expressed genes (DEGs) were identified when comparing TT and NNT. We identified four downregulated DEmiRs (miR-30a-5p, miR-432-5p, miR-487b-3p, and miR-145-5p) and six upregulated DEGs ( IL1A , MCM2 , MMP1 , MMP12 , SFN and VEGFA ) as potential biomarkers in PeC by their capacity of discriminating TT and NNT with accuracy. The integration analysis showed eight dysregulated miRNA-mRNA pairs in penile carcinogenesis. Taken together, our findings contribute to a better understanding of the regulatory roles of miRNAs and altered transcripts levels in penile carcinogenesis.

The emergence of tick-borne diseases has been reported as a serious problem in public health worldwide and many aspects of its epidemiology and effects on the health of its hosts are unclear. We aimed to perform an epidemiological study of tick-borne zoonotic Rickettsia, Borrelia, and Anaplasmataceae in horses from Midwestern Brazil. We also evaluated whether Borrelia spp. and Anaplasmataceae may be associated with hematological disorders in the sampled animals. Blood and serum samples as well as ticks were collected from 262 horses. Serum samples were used to perform serological tests, and hematological analyses were made using whole blood. Furthermore, DNA extracted from whole blood and ticks was used for molecular tests. Campo Grande is enzootic for tick-borne studied bacteria, since we found an overall exposure of 59.9% of the sampled horses, 28.7% of them presented co-exposure. Seropositivity rates of 20.6% for Borrelia spp., 25.6% for Rickettsia spp., and 31.6% for Anaplasmataceae were found in the sampled horses. Considering both molecular and serological tests for Borrelia spp., the infection rate was 48.0% (126/262). None of the tested horses showed molecular positivity for Anaplasma phagocytophilum. The horses sampled displayed 7.2% of parasitism by ixodid ticks in single and coinfestations. We did not find DNA of any studied bacteria in the sampled ticks. Positive horses for Borrelia spp. and Anaplasmataceae agents displayed leukopenia, monocytopenia, and lymphopenia. Together, our results suggest that horses may play a role as sentinel host for zoonotic bacteria and Borrelia spp. and Anaplasmataceae agents can impair the health of horses., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)