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Dyspnea is one of the most common and distressing symptoms in patients with cancer and noncancer advanced diseases. The Japanese Society for Palliative Medicine revised previous guidelines for the management of respiratory symptoms in patients with cancer and newly developed clinical guidelines for managing dyspnea in patients with advanced disease, based on the result of systematic reviews for each clinical question and consensus among experts. We describe the recommendations of the guidelines as well as provide insights into the reasoning behind the recommendations and their development process. There has been a paucity of evidence regarding the interventions for dyspnea in patients with advanced disease. Thus, more clinical research that includes not only randomized controlled trials but also real-world observational studies is warranted.

A globally implemented unified phylogenetic classification for human respiratory syncytial virus (HRSV) below the subgroup level remains elusive. We formulated global consensus of HRSV classification on the basis of the challenges and limitations of our previous proposals and the future of genomic surveillance. From a high-quality curated dataset of 1,480 HRSV-A and 1,385 HRSV-B genomes submitted to GenBank and GISAID (https://www.gisaid.org) public sequence databases through March 2023, we categorized HRSV-A/B sequences into lineages based on phylogenetic clades and amino acid markers. We defined 24 lineages within HRSV-A and 16 within HRSV-B and provided guidelines for defining prospective lineages. Our classification demonstrated robustness in its applicability to both complete and partial genomes. We envision that this unified HRSV classification proposal will strengthen HRSV molecular epidemiology on a global scale.

Background: Human rhinoviruses (RV) primarily cause the common cold, but infection outcomes vary from subclinical to severe cases, including asthma exacerbations and fatal pneumonia in immunocompromised individuals. To date, therapeutic strategies have been hindered by the high diversity of serotypes. Global surveillance efforts have traditionally focused on sequencing VP1 or VP2/VP4 genetic regions, leaving gaps in our understanding of RV genomic diversity., Methods: We sequenced 1,078 RV genomes from nasal swabs of symptomatic and asymptomatic individuals to explore viral evolution during two epidemiologically distinct periods in Washington State: when the COVID-19 pandemic affected the circulation of other seasonal respiratory viruses except for RV (February - July 2021), and when the seasonal viruses reemerged with the severe RSV and influenza outbreak (November-December 2022). We constructed maximum likelihood and BEAST-phylodynamic trees to characterize intra-genotype evolution., Results: We detected 99 of 168 known genotypes and observed inter-genotypic recombination and genotype cluster swapping from 2021 to 2022. We found a significant association between the presence of symptoms and viral load, but not with RV species or genotype. Phylodynamic trees, polyprotein selection pressure, and Shannon entropy revealed co-circulation of divergent clades within genotypes with high amino acid constraints throughout polyprotein., Discussion: Our study underscores the dynamic nature of RV genomic epidemiology within a localized geographic region, as more than 20% of existing genotypes within each RV species co-circulated each studied month. Our findings also emphasize the importance of investigating correlations between rhinovirus genotypes and serotypes to understand long-term immunity and cross-protection., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Leishmania ( Viannia ) spp. can harbor a double-stranded RNA virus known as Leishmania RNA virus 1 (LRV-1), whose presence has been reported in nine countries across the Americas and seven Leishmania species. Here, we studied 100 Leishmania ( Viannia ) isolates from patients with cutaneous leishmaniasis collected from different endemic areas in Panama from 2016 to 2022. We identified L. ( V. ) panamensis , L. ( V. ) guyanensis , L. ( V. ) braziliensis/guyanensis hybrid, and L. ( V. ) panamensis sp.1. (genetic variant). LRV-1 was detected by RT-PCR in 9% of L. (Viannia) isolates (eight cases in L. ( V. ) panamensis , and one in L. ( V. ) guyanensis) . Phylogenetic analysis based on sequencing data classified all LRV-1 isolates within genotype A, suggesting that LRV phylogenetic proximity is closely aligned with geographical distribution or to the phylogenetic proximity of the Leishmania host in the case of the L. ( V. ) panamensis and L. ( V. ) guyanensis in Panama.

Background: Rhinovirus (RV) infections can progress from the upper (URT) to lower (LRT) respiratory tract in immunocompromised individuals, causing high rates of fatal pneumonia. Little is known about how RV evolves within hosts during infection., Methods: We sequenced RV complete genomes from 12 hematopoietic cell transplant patients with infection for up to 190 days from both URT (nasal wash, NW) and LRT (bronchoalveolar lavage, BAL). Metagenomic and amplicon next-generation sequencing were used to track the emergence and evolution of intrahost single nucleotide variants (iSNVs)., Results: Identical RV intrahost populations in matched NW and BAL specimens indicated no genetic adaptation is required for RV to progress from URT to LRT. Coding iSNVs were 2.3-fold more prevalent in capsid over nonstructural genes. iSNVs modeled were significantly more likely to be found in capsid surface residues, but were not preferentially located in known RV-neutralizing antibody epitopes. Newly emergent, genotype-matched iSNV haplotypes from immunocompromised individuals in 2008-2010 could be detected in Seattle-area community RV sequences in 2020-2021., Conclusions: RV infections in immunocompromised hosts can progress from URT to LRT with no specific evolutionary requirement. Capsid proteins carry the highest variability and emergent mutations can be detected in other, including future, RV sequences., Competing Interests: Potential conflicts of interest . A. L. G. reports contract testing from Abbott, Cepheid, Novavax, Pfizer, Janssen, and Hologic; and research support from Gilead and Merck, outside of the described work. A. W. reports research support from Pfizer, Amazon, GlaxoSmithKline/Vir, Ansun Biopharma, and Allovir; receiving personal fees from Kyorin Pharmaceutical and Vir Biotechnology; and receiving grants from Amazon and VB Tech, all outside the submitted work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Tetracyclines exhibit anti-viral, anti-inflammatory, and immunomodulatory activities via various mechanisms. The present study investigated the efficacy and safety of demeclocycline in patients hospitalized with mild-to-moderate COVID-19 via an open-label, multicenter, parallel-group, randomized controlled phase 2 trial. Primary and secondary outcomes included changes from baseline (day 1, before the study treatment) in lymphocytes, cytokines, and SARS-CoV-2 RNA on day 8. Seven, seven, and six patients in the control, demeclocycline 150 mg daily, and demeclocycline 300 mg daily groups, respectively, were included in the modified intention-to-treat population that was followed until day 29. A significant change of 191.3/μL in the number of CD4 +  T cells from day 1 to day 8 was observed in the demeclocycline 150 mg group (95% CI 5.1/μL-377.6/μL) (p = 0.023), whereas that in the control group was 47.8/μL (95% CI - 151.2/μL to 246.8/μL), which was not significant (p = 0.271). The change rates of CD4 +  T cells negatively correlated with those of IL-6 in the demeclocycline-treated groups (R = - 0.807, p = 0.009). All treatment-emergent adverse events were of mild-to-moderate severity. The present results indicate that the treatment of mild-to-moderate COVID-19 patients with demeclocycline elicits immune responses conducive to recovery from COVID-19 with good tolerability.Trial registration: This study was registered with the Japan Registry of Clinical Trials (Trial registration number: jRCTs051200049; Date of the first registration: 26/08/2020)., (© 2023. Springer Nature Limited.)

Dyspnea is a prevalent symptom that significantly reduces quality of life of cancer patients. Palliative treatment is necessary when the symptoms do not respond to treatment for their cause. Opioids are widely used as pharmacological therapy, but evidence for individual agents is inconsistent. The purpose of this study was to evaluate the efficacy and safety of opioids for dyspnea in cancer patients. We searched the CENTRAL, MEDLINE, EMBASE, and ICHUSHI for studies using opioids for dyspnea in adult cancer patients reported by September 2019. Screening of the retrieved literature and assessment of risk of bias and outcomes were performed by two independent authors. A meta-analysis was performed on the primary endpoint, relief of dyspnea, and secondary endpoints including quality of life, somnolence as a side effect, and serious adverse events. Twelve randomized controlled trials were evaluated regarding relief of dyspnea. Somnolence and serious adverse events were evaluated in seven and four randomized controlled trials, respectively, but no randomized controlled trials were evaluable for quality of life. Overall, opioids were more effective than placebo for dyspnea (standardized mean difference - 0.43, 95% confidence interval [CI] - 0.75 to - 0.12). Although significant difference was found between systemic morphine and placebo in the drug-specific analysis, no significant difference could be detected in the other analyses. Systemic administration of opioids is more effective than placebo in relieving dyspnea in cancer patients. Robust evidence on the efficacy and safety of opioids on dyspnea in cancer patients is lacking, and further studies are needed., (© 2023. The Author(s).)

Background: Supplemental oxygen is widely used for dyspnea relief; however, its efficacy is yet to be verified. This study aimed to determine the efficacy of supplemental oxygen for dyspnea relief in patients with advanced progressive illness., Methods: In this systematic review, several databases, including MEDLINE and EMBASE, were searched to identify eligible randomized controlled trials (RCTs) on the topic published up to September 23, 2019. The search criteria included RCTs investigating patients with advanced progressive illness (advanced cancer, chronic obstructive pulmonary disease, and chronic heart failure). The study protocol was registered with PROSPERO (No. CRD42020161838). Separate analyses were pre-planned regarding the presence or absence of resting hypoxemia., Results: RCTs investigating supplemental oxygen for dyspnea relief in participants with and without resting hypoxemia (39 and five, respectively) were included in the study. Heterogeneity of supplemental oxygen for dyspnea in RCTs, including participants without resting hypoxemia was evident; hence, post-hoc analyses in four subgroups (supplemental oxygen during exercise or daily activities, short-burst oxygen, continuous supplemental oxygen, and supplemental oxygen during rehabilitation intervention) were conducted. In the meta-analysis, supplemental oxygen during exercise was found to improve dyspnea in patients without resting hypoxemia compared with that in the control (standardized mean difference = -0.57, 95% confidence interval = -0.77 to -0.38). However, supplemental oxygen for the other subgroups failed to improve patients' dyspnea., Conclusion: The results of this systematic review do not support supplemental oxygen therapy for dyspnea relief in patients with advanced progressive illness, except during exercise., Competing Interests: Conflict of Interest Takeo Nakayama has stock ownership or options from Bon Inc. and has received lecture fees from Pfizer Japan Inc., Janssen Pharmaceutical K·K., and Eli Lilly Japan K.K. He has also received funding from I&H Co., Ltd., Cocokarafine Group Co., Ltd., and Konica Minolta, Inc. and subsidies or donations from CancerScan and YUYAMA CO., LTD. The other authors have no conflict of interest., (Copyright © 2023 [The Author/The Authors]. Published by Elsevier B.V. All rights reserved.)

The second wave of COVID-19 occurred in South America in early 2021 and was mainly driven by Gamma and Lambda variants. In this study, we aimed to describe the emergence and local genomic diversity of the SARS-CoV-2 Lambda variant in Argentina, from its initial entry into the country until its detection ceased. Molecular surveillance was conducted on 9356 samples from Argentina between October 2020 and April 2022, and sequencing, phylogenetic, and phylogeographic analyses were performed. Our findings revealed that the Lambda variant was first detected in Argentina in January 2021 and steadily increased in frequency until it peaked in April 2021, with continued detection throughout the year. Phylodynamic analyses showed that at least 18 introductions of the Lambda variant into the country occurred, with nine of them having evidence of onward local transmission. The spatial--temporal reconstruction showed that Argentine clades were associated with Lambda sequences from Latin America and suggested an initial diversification in the Metropolitan Area of Buenos Aires before spreading to other regions in Argentina. Genetic analyses of genome sequences allowed us to describe the mutational patterns of the Argentine Lambda sequences and detect the emergence of rare mutations in an immunocompromised patient. Our study highlights the importance of genomic surveillance in identifying the introduction and geographical distribution of the SARS-CoV-2 Lambda variant, as well as in monitoring the emergence of mutations that could be involved in the evolutionary leaps that characterize variants of concern.

We sequenced 54 respiratory syncytial virus (RSV) genomes collected during 2021-22 and 2022-23 outbreaks in Washington, USA, to determine the origin of increased RSV cases. Detected RSV strains have been spreading for >10 years, suggesting a role for diminished population immunity from low RSV exposure during the COVID-19 pandemic.

Objective: the role of benzodiazepines in relieving dyspnea in patients with cancer has not yet been established. This systematic review and meta-analysis aimed to determine the efficacy and safety of benzodiazepines alone or in combination with opioids for dyspnea in patients with cancer., Methods: Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and Ichushi-Web were searched for articles published from database inception to 23 September 2019. Studies of benzodiazepines alone or in combination with opioids for dyspnea were included. The primary outcome measure was the relief of dyspnea. The secondary outcome measures were anxiety, somnolence and severe adverse events., Results: of 505 publications initially identified, two trials and one trial were included in the meta-analysis of midazolam alone and in combination with morphine, respectively. With regard to the relief of dyspnea, midazolam alone showed no significant difference compared with morphine alone, with a relative risk of 0.95 (95% confidence interval: 0.47-1.89). Meanwhile, midazolam plus morphine was significantly more effective than morphine alone, with a relative risk of 1.33 (95% confidence interval: 1.02-1.75). For anxiety relief, a meta-analysis could not be performed because of insufficient data. The incidence of somnolence and severe adverse events was not significantly different between the experimental and control groups for either midazolam alone or in combination with morphine., Conclusions: benzodiazepines alone do not significantly improve dyspnea compared with opioids alone, but a combination of benzodiazepines and opioids may be more effective. Evidence from randomized controlled trials focusing on patients with cancer has not been generated in recent years. Further appropriately designed randomized controlled trials are required., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Introduction: Coinfection with two SARS-CoV-2 viruses is still a very understudied phenomenon. Although next generation sequencing methods are very sensitive to detect heterogeneous viral populations in a sample, there is no standardized method for their characterization, so their clinical and epidemiological importance is unknown., Material and Methods: We developed VICOS (Viral COinfection Surveillance), a new bioinformatic algorithm for variant calling, filtering and statistical analysis to identify samples suspected of being mixed SARS-CoV-2 populations from a large dataset in the framework of a community genomic surveillance. VICOS was used to detect SARS-CoV-2 coinfections in a dataset of 1,097 complete genomes collected between March 2020 and August 2021 in Argentina., Results: We detected 23 cases (2%) of SARS-CoV-2 coinfections. Detailed study of VICOS's results together with additional phylogenetic analysis revealed 3 cases of coinfections by two viruses of the same lineage, 2 cases by viruses of different genetic lineages, 13 were compatible with both coinfection and intra-host evolution, and 5 cases were likely a product of laboratory contamination., Discussion: Intra-sample viral diversity provides important information to understand the transmission dynamics of SARS-CoV-2. Advanced bioinformatics tools, such as VICOS, are a necessary resource to help unveil the hidden diversity of SARS-CoV-2., Competing Interests: Declaration of Competing Interest The authors declare no competing interest or personal relationship that might have affected the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Globally, the human respiratory syncytial virus (RSV) is one of the major causes of lower respiratory tract infections (LRTIs) in children. The scarcity of complete genome data limits our understanding of RSV spatiotemporal distribution, evolution, and viral variant emergence. Nasopharyngeal samples collected from hospitalized pediatric patients from Buenos Aires tested positive for RSV LRTI during four consecutive outbreaks (2014-2017) were randomly subsampled for RSV complete genome sequencing. Phylodynamic studies and viral population characterization of genomic variability, diversity, and migration of viruses to and from Argentina during the study period were performed. Our sequencing effort resulted in one of the largest collections of RSV genomes from a given location (141 RSV-A and 135 RSV-B) published so far. RSV-B was dominant during the 2014-2016 outbreaks (60 per cent of cases) but was abruptly replaced by RSV-A in 2017, with RSV-A accounting for 90 per cent of sequenced samples. A significant decrease in RSV genomic diversity-represented by both a reduction in genetic lineages detected and the predominance of viral variants defined by signature amino acids-was observed in Buenos Aires in 2016, the year prior to the RSV subgroup predominance replacement. Multiple introductions to Buenos Aires were detected, some with persistent detection over seasons, and also, RSV was observed to migrate from Buenos Aires to other countries. Our results suggest that the decrease in viral diversity may have allowed the dramatic predominance switch from RSV-B to RSV-A in 2017. The immune pressure generated against circulating viruses with limited diversity during a given outbreak may have created a fertile ground for an antigenically divergent RSV variant to be introduced and successfully spread in the subsequent outbreak. Overall, our RSV genomic analysis of intra- and inter-outbreak diversity provides an opportunity to better understand the epochal evolutionary dynamics of RSV., (© The Author(s) 2023. Published by Oxford University Press.)

The COVID-19 pandemic has lately been driven by Omicron. This work aimed to study the dynamics of SARS-CoV-2 Omicron lineages during the third and fourth waves of COVID-19 in Argentina. Molecular surveillance was performed on 3431 samples from Argentina, between EW44/2021 and EW31/2022. Sequencing, phylogenetic and phylodynamic analyses were performed. A differential dynamic between the Omicron waves was found. The third wave was associated with lineage BA.1, characterized by a high number of cases, very fast displacement of Delta, doubling times of 3.3 days and a low level of lineage diversity and clustering. In contrast, the fourth wave was longer but associated with a lower number of cases, initially caused by BA.2, and later by BA.4/BA.5, with doubling times of about 10 days. Several BA.2 and BA.4/BA.5 sublineages and introductions were detected, although very few clusters with a constrained geographical distribution were observed, suggesting limited transmission chains. The differential dynamic could be due to waning immunity and an increase in population gatherings in the BA.1 wave, and a boosted population (for vaccination or recent prior immunity for BA.1 infection) in the wave caused by BA2/BA.4/BA.5, which may have limited the establishment of the new lineages.

Background: Pimobendan is widely used for the treatment of dogs with heart failure via the oral route. A new injectable form of pimobendan is now available and its potential usefulness via intravenous route has been recently demonstrated in dogs. However, the cardiovascular effects of intramuscular (IM) administration of injectable pimobendan have not been investigated yet., Hypothesis: IM administration of pimobendan may have the same hemodynamic effect as the IV route., Methods: Six healthy Beagle dogs underwent a placebo-controlled double-blind crossover study. The early cardiovascular effects after a single dose of IM and IV injections of pimobendan (0.2 ml/kg; Pimo IM and Pimo IV, respectively) were compared to the same volume of IM placebo (Saline IM) in anesthetized dogs. Clinical [heart rate (HR) and blood pressure (BP)] and echocardiographic hemodynamic parameters [left ventricular (LV) inflow waveforms of diastolic early wave (eV), atrial systolic wave (aV), diastolic early mitral ring velocity (e'), peak velocity (pV), stroke volume (SV), cardiac output (CO), and systemic vascular resistance (SVR)] were monitored with 15 min intervals for 120 min., Results: Diastolic BP decreased significantly at 30 min in Pimo IM compared to Saline IM. Mean eV and CO values significantly increased from 75 min, e' from 60 min, pV from 75 min, and SV from 15 to 120 min, whereas SVR significantly decreased at 30-60 min in Pimo IM compared to those of Saline IM ( P < 0.05). Compared with the Pimo IV, eV and pV were significantly lower at 30-60 min ( P < 0.05) while SV was significantly higher at 90-105 min in Pimo IM ( P < 0.05). Other hemodynamic parameters (BP, HR, SVR, CO, e', and E/e') did not significantly change between Pimo IM and IV., Conclusions: The hemodynamic effect of pimobendan following IM and IV injection was described. Our results suggested that IM administration of pimobendan is equally comparable and possibly interchangeable with IV administration. This warrant further studies to investigate the clinical effectiveness of IM pimobendan in treating dogs with congestive heart failure or in heart failure cases unable to receive IV or oral administration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor HS declared a past co-authorship with the authors ASM and RT., (Copyright © 2022 Enokizono, Mandour, Komeda, Goya, Takeuchi, Katoh, Yairo, Yilmaz, Shimada and Tanaka.)

Background: Novel non-invasive evaluation of the intraventricular pressure differences and gradients (IVPD and IVPG) by color M-mode echocardiography (CMME) is a promising method in diastolic function evaluation. Patent ductus arteriosus (PDA) is a congenital heart defect which is associated with increased preload. The present work provides a clinical trial for the assessment of IVPD and IVPG changes in dogs before and after surgical occlusion of PDA., Materials and Methods: A total of 12 client-owned dogs were enrolled in this study. PDA was confirmed using echocardiography, and all dogs underwent PDA occlusion. Conventional echocardiography and CMME were conducted on each patient on the operation day (Pre-PDA) and 48 h after its occlusion (Post-PDA). The total IVPD and total IVPG, as well as segmental intraventricular pressure (basal, mid-to-apical, mid, and apical) were measured from Euler's equation using specific software (MATLAB). Data were analyzed for variability and for the difference between pre- and post-PDA. The effect of PDA occlusion on the measured variables was calculated using biserial ranked correlation (rc)., Results: There was a significant reduction in end-diastolic volume, fraction shortening, stroke volume, and mitral inflow velocities (early and late) after PDA closure. CMME was feasible in all dogs, and the CMME indices showed moderate variability, except for the apical segment of IVPD and IVPG. After PDA closure, in comparison with the pre-PDA occlusion, there was a significant reduction in total IVPD (2.285 ± 0.374 vs. 1.748 ± 0.436 mmHg; P = 0.014), basal IVPD (1.177 ± 0.538 vs. 0.696 ± 0.144 mmHg; P = 0.012), total IVPG (1.141 ± 0.246 vs. 0.933 ± 0.208 mmHg; P = 0.032), and basal IVPG (0.578 ± 0.199 vs. 0.377 ± 0.113 mmHg; P = 0.001); meanwhile, mid, mid-to-apical, and apical segments of both IVPD and IVPG showed non-significant difference. The magnitude of PDA occlusion on the measured variables was clinically relevant and associated with a large effect size on total and basal IVPD and IVPG (rc > 0.6)., Conclusion: The current clinical study revealed matched response of IVPD and IVPG to the reduced preload rather than left ventricular relaxation. This result is an initial step in the clinical utility of CMME-derived IVPD and IVPG measurements in the diastolic function evaluation in dogs with PDA that warrants further clinical studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor HS declared a past co-authorship with the authors ASM and RT., (Copyright © 2022 Hirose, Mandour, Goya, Hamabe, Matsuura, Yoshida, Watanabe, Shimada, Uemura, Takahashi and Tanaka.)

Background: Acute lymphoblastic leukemia (ALL) is a malignant clonal bone marrow disorder with a high mortality rate during the initial therapy. This retrospective study aimed to describe and analyze the risk factors and causes of induction-related mortality (IRM) in an adolescent and adult ALL population treated in a low- and middle-income country., Methods: From 2009 to 2016, a total of 167 patients were included, of which 50.9% were male with a median age of 28 years. B-immunophenotype represented 97.6%, and high-risk cytogenetics were present in 23.3%. During induction therapy, 91% had at least 1 complication, most of which were infectious, with an IRM of 12%., Results: Factors associated with increased mortality rate were central nervous system (CNS) status [CNS-3: hazard ratio (HR) 3.029; 95% confidence interval (CI), 0.79‒11.49; P =0.103 and CNS-2: HR, 9.98; 95% CI, 2.65‒37.65; P =0.001] and dialysis requirement (HR, 9.15; 95% CI, 2.44‒34.34; P =0.001)., Conclusion: Our study confirms that ALL patients treated in resource-constrained settings have high rates of IRM, mainly attributed to advanced disease and high tumor burden at diagnosis.

The type Aii shunt is a congenital extrahepatic portosystemic shunt (ePSS) involving the left and right gastric vein and the caudal vena cava (CVC). This report describes the case of a 6-month-old Italian greyhound diagnosed with a type Aii large-diameter ePSS. Staged surgeries were employed to completely ligate the 2 gastric veins and to avoid the risk of traumatizing the shunt vessel, CVC, and celiac artery. Clinical signs improved postoperatively, and after 3 years, ultrasonography demonstrated no evidence of reoccurrence. This procedure provides an alternative surgical option for correction of ePSS type Aii. Key clinical message: This case report demonstrates congenital PSS involving the left and right gastric vein and the caudal vena could be treated with both ligation of left and right gastric vein. This technique could decrease the risk of traumatizing the shunt vessel, CVC, and celiac artery., (Copyright and/or publishing rights held by the Canadian Veterinary Medical Association.)

SARS-CoV-2 variants with concerning characteristics have emerged since the end of 2020. Surveillance of SARS-CoV-2 variants was performed on a total of 4,851 samples from the capital city and 10 provinces of Argentina, during 51 epidemiological weeks (EWs) that covered the end of the first wave and the ongoing second wave of the COVID-19 pandemic in the country (EW 44/2020 to EW 41/2021). The surveillance strategy was mainly based on Sanger sequencing of a Spike coding region that allows the identification of signature mutations associated with variants. In addition, whole-genome sequences were obtained from 637 samples. The main variants found were Gamma and Lambda, and to a lesser extent, Alpha, Zeta, and Epsilon, and more recently, Delta. Whereas, Gamma dominated in different regions of the country, both Gamma and Lambda prevailed in the most populated area, the metropolitan region of Buenos Aires. The lineages that circulated on the first wave were replaced by emergent variants in a term of a few weeks. At the end of the ongoing second wave, Delta began to be detected, replacing Gamma and Lambda. This scenario is consistent with the Latin American variant landscape, so far characterized by a concurrent increase in Delta circulation and a stabilization in the number of cases. The cost-effective surveillance protocol presented here allowed for a rapid response in a resource-limited setting, added information on the expansion of Lambda in South America, and contributed to the implementation of public health measures to control the disease spread in Argentina., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Torres, Mojsiejczuk, Acuña, Alexay, Amadio, Aulicino, Debat, Fay, Fernández, Giri, Goya, König, Lucero, Nabaes Jodar, Pianciola, Sfalcin, Acevedo, Bengoa Luoni, Bolatti, Brusés, Cacciabue, Casal, Cerri, Chouhy, Dus Santos, Eberhardt, Fernandez, Fernández, Fernández Do Porto, Formichelli, Gismondi, Irazoqui, Campos, Lusso, Marquez, Muñoz, Mussin, Natale, Oria, Pisano, Posner, Puebla, Re, Sosa, Villanova, Zaiat, Zunino, Acevedo, Acosta, Alvarez Lopez, Álvarez, Angeleri, Angelletti, Arca, Ayala, Barbas, Bertone, Bonnet, Bourlot, Cabassi, Castello, Castro, Cavatorta, Ceriani, Cimmino, Cipelli, Colmeiro, Cordero, Cristina, Di Bella, Dolcini, Ercole, Espasandin, Espul, Falaschi, Fernandez Moll, Foussal, Gatelli, Goñi, Jofré, Jaramillo, Labarta, Lacaze, Larreche, Leiva, Levin, Luczak, Mandile, Marino, Massone, Mazzeo, Medina, Monaco, Montoto, Mugna, Musto, Nadalich, Nieto, Ojeda, Piedrabuena, Pintos, Pozzati, Rahhal, Rechimont, Remes Lenicov, Rompato, Seery, Siri, Spina, Streitenberger, Suárez, Suárez, Sujansky, Talia, Theaux, Thomas, Ticeira, Tittarelli, Toro, Uez, Zaffanella, Ziehm, Zubieta, Mistchenko, Valinotto and Viegas.)

Early detection of doxorubicin (DXR)-induced cardiomyopathy (DXR-ICM) is crucial to improve cancer patient outcomes and survival. In recent years, the intraventricular pressure gradient (IVPG) has been a breakthrough as a sensitive index to assess cardiac function. This study aimed to evaluate the usefulness of IVPG for the early detection of chemotherapy-related cardiac dysfunction. For this purpose, six dogs underwent conventional, speckle tracking, and color M-mode echocardiography concomitantly with pressure-and-volume analysis by conductance catheter. The cardiac function measurements were assessed before DXR administration (baseline, Pre), at the end of treatment protocol (Post), and at 1.5 years follow-up (Post2). The result showed a significant reduction in the left ventricular end-systolic pressure-volume (Emax: 4.4 ± 0.7, 6.1 ± 1.6 vs. 8.4 ± 0.8 mmHg/mL), total-IVPG (0.59 ± 0.12, 0.62 ± 0.15 vs. 0.86 ± 0.12 mmHg), and mid-IVPG (0.28 ± 0.12, 0.31 ± 0.11 vs. 0.48 ± 0.08 mmHg), respectively in Post2 and Post compared with the baseline ( p < 0.05). Mid-to-apical IVPG was also reduced in Post2 compared with the baseline (0.29 ± 0.13 vs. 0.51 ± 0.11). Meanwhile, the fraction shortening, ejection fraction, and longitudinal strain revealed no change between groups. Total and mid-IVPG were significantly correlated with Emax (R = 0.49; p < 0.05, both) but only mid-IVPG was a predictor for Emax (R 2 = 0.238, p = 0.040). In conclusion, this study revealed that impairment of contractility was the initial changes observed with DXR-ICM in dogs and only IVPG could noninvasively detect subclinical alterations in cardiac function. Color M-mode echocardiography-derived IVPG could be a potential marker for the early detection of doxorubicin cardiomyopathy.

Pulmonary hypertension (PH) is a disease with poor prognosis, and it is characterized by the progressive elevation of pulmonary vascular resistance and pressure. Various factors are associated with the pathology of PH, including AMP-activated protein kinase (AMPK) deficiency. The present study aimed to evaluate the therapeutic effect of metformin, an AMPK activator, in a monocrotaline (MCT)-induced PH rat model. Rats were randomly divided into the following three groups: i) Saline-injected group (sham group); ii) monocrotaline (MCT)-injected group (PH group); iii) MCT-injected and metformin-treated group (MT group). Four weeks following MCT injection, cardiac ultrasonography, invasive hemodynamic measurements, measurement of serum levels of big endothelin-1 (big ET-1) and histological analysis were performed to evaluate the effect of metformin treatment in PH. Pulmonary arterial pressure and serum big ET-1 concentrations were reduced in the MT group compared with the PH group. Medial wall thickness and wall area of the pulmonary arterioles in the MT group were decreased compared with the PH group. Comparing the right heart functional parameters among groups revealed that the acceleration time/ejection time ratio improved in the MT group compared with the PH group. Thus, the present study demonstrated the efficacy of metformin in an MCT-induced PH rat model and suggested that metformin may be a valuable, potential novel therapeutic for the treatment of PH., (Copyright: © Yoshida et al.)

Introduction: Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infection (ALRTI) in pediatrics. Preterm infants are at a higher risk for complications. We aimed to describe and compare the clinical and epidemiological characteristics associated with ALRTI due to RSV in preterm and term infants and to establish the predictors of fatality among preterm infants., Methods: Prospective, cross-sectional study of patients admitted due to ALRTI in the 2000-2018 period. Viral diagnosis was done by indirect immunofluorescence or reverse transcription polymerase chain reaction in nasopharyngeal aspirates. Clinical and epidemiological characteristics were recorded. A multiple logistic regression model established the predictors of fatality among preterm infants., Results: A total of 16 018 ALRTI cases were included; 13 545 (84.6 %) were tested; 6047 (45 %) were positive; RSV was prevalent in 81.1 % (4907), with a seasonal epidemic pattern; 14 % (686) were preterm infants. Comorbidities, perinatal respiratory history, congenital heart disease, malnutrition, chronic respiratory disease, bronchopulmonary dysplasia, prior hospitalization due to ALRTI, and chronic neurological disease (p < 0.001) were more common among preterm infants; they required more intensive care and a longer length of stay, and had a higher fatality rate (p < 0.01). Congenital heart disease was an independent predictor of fatality due to RSV among preterm infants (OR: 3.67 [1.25-10.8], p = 0.01)., Conclusion: RSV showed an epidemic pattern and affected more preterm infants with certain comorbidities, with a higher morbidity and mortality, compared to term infants. RSV fatality among preterm infants was associated with congenital heart disease., Competing Interests: None, (Sociedad Argentina de Pediatría.)

The goal of this study was to evaluate diastolic intraventricular pressure gradients (IVPG) and 2-dimensional tissue tracking (2DTT) patterns during diabetes and cardiomyopathy. Rats ( n = 60) were induced to become diabetic (DM group, n = 15) by using streptozotocin, to become cardiomyopathic (CM group, n = 15) by using isoproterenol, and to become both diabetic and cardiomyopathic (DMCM group, n = 15); control rats (CT group, n = 15) were injected with saline. Two months after induction, all rats underwent conventional echocardiography, IVPG, and 2DTT and then were euthanized for microscopic examination of cardiac fibrosis. Compared with the controls, all 3 treated groups showed diastolic dysfunction and delayed cardiac relaxation. DMCM rats showed the most pronounced cardiac abnormalities. In addition, CM and DMCM groups had showed decreased middle IVPG, whereas DMCM rats had decreased midapical IVPG. Although the overall IVPG of the CM group was normal, the middle segment was significantly decreased. 2DTT results showed that the DMCM group had a delay in relaxation compared with other groups. IVPG and 2DTT can be used to overcome the limitation of conventional echocardiographic methods and reveal diastolic dysfunction. DM worsened diastolic function during cardiac disease.

Long-term therapy-related reproductive health side effects impact the quality of life of hematopoietic stem cell transplantation (HSCT) survivors. In this study, we evaluated the prevalence of gonadal dysfunction (GD) pre- and post-HSCT, analyzed factors associated with GD, and explored rates of fertility assessment (FA) and fertility preservation (FP) in a resource-limited setting. FA and outcomes of patients age ≤45 years undergoing HSCT between June 2000 and May 2018 were collected retrospectively. We included 213 patients with a median age of 26 years. Pre-HSCT FA was performed in 71.8%, with a GD rate of 17%. The rate of GD was not different between the sexes (females, 19.5% versus males, 16.1%; P = .616) and was only associated with increasing age. The rate of cryopreservation in the cohort was 3.3%. Almost one-half (47.7%) of post-HSCT patients completed FA and evidenced an increase in GD rate to 48.9%. Comparing pre-HSCT and post-HSCT GD rates, women had a significant increase (19.5% versus 81.4%; P < .001), whereas men did not (16.1% versus 20.4%; P = .76). These results were confirmed by a multiple imputation analysis accounting for missing data. Female sex, pre-HSCT cytotoxic therapy, myeloablative conditioning, and germ cell tumor (GCT) diagnosis were associated with post-HSCT GD. Reproductive health preservation can be positively impacted when FA and FP are prioritized at the initial diagnosis in HSCT candidates, particularly in women of older age and men with a diagnosis of GCT. The low FP success observed urges implementation of strategies that favor accessibility and improve quality of life of HSCT survivors in low- and middle-income countries., (Copyright © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Mesothelioma is an aggressive tumor originating from mesothelial cells. Mesothelioma of the spermatic cord is a very rare disease, and the most common presentation of this disease is that of aggressive mesothelioma with no description of mesothelioma in situ. We report an extremely rare case of mesothelioma in situ of the spermatic cord arising from a patent processus vaginalis. To our best knowledge, this is the first report of this finding. The identification of a patent processus vaginalis and investigation of single-layered atypical mesothelial cells led to the final diagnosis.

Purpose: To study the diastolic functions using color Doppler M-mode (CDMM) for noninvasive analysis of the intraventricular pressure difference (IVPD) in diabetic rats., Methods: Two equal groups of rats were included: control and streptozotocin-induced DM (n = 15). The cardiac functions were examined monthly using conventional echocardiography and CDMM with a specific MATLAB software. Echocardiography was performed under 2% isoflurane mask inhalation. Five months thereafter, all rats were killed for macroscopic and microscopic examinations of the cardiac fibrosis., Results: DM rats showed higher systolic blood pressure and diastolic dysfunction, i.e., decreases in several parameters such as E, E/A, TDIs, and IVPDs, compared to the controls. Moreover, obvious cardiac fibrosis was seen in perivascular and interstitial tissues, but there were no notable differences in terms of gross lesions., Conclusions: Because of the noninvasive nature of CDMM, IVPD and other conventional echocardiographic parameters can be used as reliable indicators generally for evaluating cardiac function and particularly the change in intraventricular pressure.