Pilot Assessment of Platelet Thrombus Area and Contractile Force in Pediatric Congenital Heart Surgery Patients Using a Microfluidic Device.

OBJECTIVES: This work was designed to evaluate maximum platelet contractile force and thrombus area before and after cardiopulmonary bypass (CPB) in pediatric patients having congenital heart disease (CHD) surgery using a microfluidic device. DESIGN: A prospective cohort study was designed. SETTING: The work took place at an academic medical center. PARTICIPANTS: Twenty pediatric CHD patients ≤8 years of age with expected CPB time >30 minutes were enrolled. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Blood was collected at baseline and post-CPB. Maximum platelet contractile force and thrombus area were evaluated in vitro using a microfluidic device (ATLAS PST). Post-CPB samples were supplemented with recombinant von Willebrand factor (rVWF) to explore the impact on contractile force and thrombus area. At baseline, the maximum thrombus area was 0.06 (0.05, 0.07), and the maximum force was 123.3 nN (68.4, 299.5). Linear mixed-effects regression models showed that the maximum thrombus area was larger post-CPB and post-CPB + rVWF compared with pre-CPB (estimated coefficient [Est] = 0.04, p = 0.002; Est = 0.09, p < 0.001, respectively). The maximum thrombus area was also larger post-CPB + rVWF compared with post-CPB (Est = 0.04, p = 0.001). Force was higher post-CPB + rVWF compared with pre-CPB (Est = 173.32, p = 0.044). CONCLUSIONS: In pediatric CHD patients, microfluidic testing demonstrated that platelet thrombus area increased slightly after CPB, while platelet contractile force did not change. In vitro addition of rVWF further increased thrombus area, suggesting augmentation of primary hemostasis. Microfluidic assessment of platelet contractile force and thrombus area in pediatric CHD patients appears feasible and can demonstrate changes after CPB. Further studies are needed to determine its accuracy, clinical utility, and normal values for pediatric patients.

The Impact of Nasal Intubation on Feeding Outcomes in Neonates Requiring Cardiac Surgery: A Randomized Control Trial.

Neonates who require surgery for congenital heart disease (CHD) frequently have difficulty with oral feeds post-operatively and may require a feeding tube at hospital discharge. The purpose of this study was to determine the effect of oral or nasal intubation route on feeding method at hospital discharge. This was a non-blinded randomized control trial of 62 neonates who underwent surgery for CHD between 2018 and 2021. Infants in the nasal (25 patients) and oral (37 patients) groups were similar in terms of pre-operative risk factors for feeding difficulties including completed weeks of gestational age at birth (39 vs 38 weeks), birthweight (3530 vs 3100 g), pre-operative PO intake (92% vs 81%), and rate of pre-operative intubation (22% vs 28%). Surgical risk factors were also similar including Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery category (3.9 vs 4.1), shunt placement (32% vs 41%), cardiopulmonary bypass time (181 vs 177 min), and cross-clamp time (111 vs 105 min). 96% of nasally intubated patients took full oral feeds by discharge as compared with 78% of orally intubated infants (p = 0.05). Nasally intubated infants reach full oral feeds an average of 3 days earlier than their orally intubated peers. In this cohort of patients, nasally intubated infants reach oral feeds more quickly and are less likely to require supplemental tube feeding in comparison to orally intubated peers. Intubation route is a potential modifiable risk factor for oral aversion and appears safe in neonates. The study was approved by the University of Virginia Institutional Review Board for Health Sciences Research and was retrospectively registered on clinicaltrials.gov (NCT05378685) on May 18, 2022.

Metabarcoding approach to identify bacterial community profiling related to nosocomial infection and bacterial trafficking-routes in hospital environments.

Nosocomial infections (NIs) appear in patients under medical care in the hospital. The surveillance of the bacterial communities employing high-resolution 16S rRNA profiling, known as metabarcoding, represents a reliable method to establish factors that may influence the composition of the bacterial population during NIs. The present study aimed to utilize high-resolution 16S rRNA profiling to identify high bacterial diversity by analyzing 11 inside and 10 outside environments from the General Hospital of Ribeirão Preto Medical School, Brazil. Our results identified a high bacterial diversity, and among these, the most abundant bacterial genera linked to NIs were Cutibacterium, Streptococcus, Staphylococcus, and Corynebacterium. A Acinetobacter was detected in cafeterias, bus stops, and adult and pediatric intensive care units (ICUs). Data suggest an association between transport and alimentation areas proximal to the hospital ICU environment. Interestingly, the correlation and clusterization analysis showed the potential of the external areas to directly influence the ICU pediatric department microbial community, including the outpatient's clinic, visitor halls, patient reception, and the closest cafeterias. Our results demonstrate that high-resolution 16S rRNA profiling is a robust and reliable tool for bacterial genomic surveillance. In addition, the metabarcoding approach might help elaborate decontamination policies, and consequently reduce NIs.

Bronchobiliary fistula after stenting of biliary duct as the management of iatrogenic bile duct injury during elective cholecystectomy.

BACKGROUND: Bronchobiliary fistula is a rare and complex entity defined by an abnormal communication between the biliary and bronchial systems. The etiopathogenesis is not completely understood, but the most common factors implicated are hepatobiliary tumors, biliary obstruction, iatrogenic damage or trauma. METHODS: Here we present a case of a 69-year-old man that developed a bronchobiliary fistula and a pulmonary abscess after migration of a bile duct stent placed as part of the treatment of an iatrogenic bile duct injury that occurred during elective cholecystectomy. RESULTS: A conservative approach, that included broad-spectrum antibiotic, removal of the stent, and sphincterotomy, was enough for the closure of the fistula and resolution of the symptoms. CONCLUSION: We emphasize the importance of prompt recognition of this entity and a concerted therapeutic strategy to optimize the probability of success, avoiding the destructive consequences of the bile in the pulmonary parenchyma and septic complications.

Combined superior mesenteric artery syndrome and nutcraker syndrome presenting as acute pancreatitis: a case report.

Superior mesenteric artery syndrome designates compression of the third part of the duodenum between the superior mesenteric artery and the aorta. This condition has a low incidence, being more common in thin young women. Nutcracker syndrome is compression of the left renal vein between the superior mesenteric artery and the aorta. Both entities are rare, and their coexistence has been reported in a few cases. Conservative treatment targeting weight gain is sufficient in most cases. An association between the superior mesenteric artery syndrome and acute pancreatitis has rarely been reported. We intend to describe the case of an 18-year-old girl who was admitted to the emergency room with epigastric pain and emesis. Our investigation revealed acute acalculous pancreatitis. During work-up, we discovered superior mesenteric artery syndrome and a compressed left renal vein. The patient is on conservative treatment, and her symptoms have improved.

A síndrome da artéria mesentérica superior designa compressão da terceira parte do duodeno pela artéria mesentérica superior e a aorta. Essa condição tem uma baixa incidência, sendo mais comum em mulheres jovens magras. A síndrome de quebra-nozes resulta da compressão da veia renal esquerda pela artéria mesentérica superior e a aorta. Ambas as entidades são raras, e a sua coexistência foi descrita em poucos casos. Tratamento conservador com o objetivo de ganho ponderal é suficiente na maioria dos casos. A associação entre a síndrome da artéria mesentérica superior e a pancreatite aguda foi raramente relatada. Pretendemos descrever o caso de uma jovem de 18 anos que recorreu ao serviço de urgência com epigastralgia e vômitos. A investigação realizada revelou pancreatite aguda alitiásica. Durante o estudo complementar, foi identificada a síndrome da artéria mesentérica superior, bem como uma veia renal esquerda comprimida. A paciente encontra-se em tratamento conservador, apresentando melhora clínica.

Lamin A/C recruits ssDNA protective proteins RPA and RAD51 to stalled replication forks to maintain fork stability.

Lamin A/C provides a nuclear scaffold for compartmentalization of genome function that is important for genome integrity. Lamin A/C dysfunction is associated with cancer, aging, and degenerative diseases. The mechanisms whereby lamin A/C regulates genome stability remain poorly understood. We demonstrate a crucial role for lamin A/C in DNA replication. Lamin A/C binds to nascent DNA, especially during replication stress (RS), ensuring the recruitment of replication fork protective factors RPA and RAD51. These ssDNA-binding proteins, considered the first and second responders to RS respectively, function in the stabilization, remodeling, and repair of the stalled fork to ensure proper restart and genome stability. Reduced recruitment of RPA and RAD51 upon lamin A/C depletion elicits replication fork instability (RFI) characterized by MRE11 nuclease-mediated degradation of nascent DNA, RS-induced DNA damage, and sensitivity to replication inhibitors. Importantly, unlike homologous recombination-deficient cells, RFI in lamin A/C-depleted cells is not linked to replication fork reversal. Thus, the point of entry of nucleases is not the reversed fork but regions of ssDNA generated during RS that are not protected by RPA and RAD51. Consistently, RFI in lamin A/C-depleted cells is rescued by exogenous overexpression of RPA or RAD51. These data unveil involvement of structural nuclear proteins in the protection of ssDNA from nucleases during RS by promoting recruitment of RPA and RAD51 to stalled forks. Supporting this model, we show physical interaction between RPA and lamin A/C. We suggest that RS is a major source of genomic instability in laminopathies and lamin A/C-deficient tumors.

Best additional management after non-curative endoscopic resection of esophageal squamous cell carcinoma: a systematic review and meta-analysis.

INTRODUCTION: Endoscopic resection (ER) is an accepted first-line treatment for superficial esophageal squamous cell carcinoma (ESCC), but when curative resection is not achieved, further treatment is not standardised. We aimed at evaluating outcomes of management strategies (esophagectomy, chemoradiotherapy/radiotherapy (CRT/RT) or follow-up (FUP)) after a non-curative ESCC ER. METHODS: A systematic review was performed evaluating outcomes of different management strategies after ESCC submitted to primary ER (T1a/T1b), without curative criteria (R1/Rx, T1a-m3/T1b, lymphovascular invasion (LVI) or poor differentiation). Primary outcomes included recurrence, overall survival (OS) and cancer-specific survival (CSS). Secondary outcomes consisted of treatment-related adverse events. RESULTS: Seventeen studies were included for qualitative analysis (16 observational and 1 randomized controlled trial) including 788 patients with ESCC submitted to ER, managed by additional CRT/RT (n = 530), surgery (n = 98) or FUP (n = 160). Eight studies suited quantitative analysis. Patients only followed up after ER experienced recurrence rates of 0-36.4% (OR 3.6 (95%CI 1.06-12.20) vs further treatments). When submitted to CRT/RT following non-curative ER, recurrence was observed in 0-27.2% (OR 8.00 (95%CI 1.74-36.80) whereas after surgery no recurrence was noticeable. Reported 5 y-OS after CRT/RT for non-curative ER ranged among 75-100% whereas, for those offered surgeries, 5 y-OS was 89.5%. OS ranged between 54.5% and 100% after FUP. CRT/RT and surgery-related adverse events ranged from 0% to 32% and 14% to 28.5%. CONCLUSIONS: Additional treatment should be provided in ESCC after non-curative ER. Adjuvant esophagectomy might be the preferred treatment to medically fit patients with high-risk features (namely LVI). Properly designed trials assessing the role of CRT/RT are needed to manage these patients.

Ultra-low dose radiotherapy in the management of low-grade orbital lymphomas.

Background: Ultra-low dose radiotherapy (ULDRT) (2 × 2 Gy) has been used for symptomatic control of low-grade lymphomas with surprising local control rates, suggesting that these entities could respond to lower doses. These are particularly desirable for the treatment of orbital sites and some publications refer to high rates of complete responses. In this paper, we present our experience with the use of ULDRT for indolent orbital lymphomas. Materials and methods: Electronic files and treatment plans of patients treated with ULDRT for low-grade orbital lymphoma were retrospectively reviewed. Oncological outcomes and toxicities were collected and described for each patient. Results: Seven patients (median age of 75 years) with 8 lesions (3 follicular, 2 MALT, 1 marginal and 1 low-grade non-Hodgkin lymphoma) were considered for analysis. The majority had stage IE disease and one patient had bilateral disease. Six tumors were detected on imaging (median size of 20 mm). Involved orbital sites were periocular, conjunctival and palpebral; there was one case of intraocular (choroid) and one case of lacrimal gland involvement. One patient received consolidative rituximab after RT. The median follow-up time was 22 months. Two patients had partial response, one of them with persistent minimal choroidal disease and the other with partial response on CT. Five (71%) patients had clinical (n = 2) or radiologic (n = 3) complete response on treated sites. Reported late toxicities were minimal and included dry eye and pruritus. Conclusion: In our experience, ULDRT achieved a local control rate of 100% and complete response rate of 71% with minimal toxicity.

Renal lipotoxicity: Insights from experimental models.

In recent decades, there has been a progressive increase in the prevalence of obesity and chronic kidney disease. Renal lipotoxicity has been associated with obesity. Although lipids play fundamental physiological roles, the accumulation of lipids in kidney cells may cause dysfunction and/or renal fibrosis. Adipose tissue that exceeds their lipid storage capacity begins to release triglycerides into the bloodstream that can get stored in several organs, including the kidneys. The mechanisms underlying renal lipotoxicity involve intracellular lipid accumulation and organelle dysfunction, which trigger oxidative stress and inflammation that consequently result in insulin resistance and albuminuria. However, the specific pathways involved in renal lipotoxicity have not yet been fully understood. We aimed to summarize the current knowledge on the mechanisms by which lipotoxicity affects the renal morphology and function in experimental models of obesity. The accumulation of fatty acids in tubular cells has been described as the main mechanism of lipotoxicity; however, lipids and their metabolism also affect the function and the survival of podocytes. In this review, we presented indication of mitochondrial, lysosomal and endoplasmic reticulum alterations involved in kidney damage caused by obesity. The kidney is vulnerable to lipotoxicity, and studies of the mechanisms underlying renal injury caused by obesity can help identify therapeutic targets to control renal dysfunction.

Steinernema diaprepesi Nguyen & Duncan (Rhabditida: Steinernematidae), a new entomopathogenic nematode from Brazil.

Entomopathogenic nematodes (EPNs) can control pests due to their mutual association with bacteria. The use of these biological control agents is increasing worldwide due to advances in research about its control efficiency, range of action and mass production. The identification of EPNs adapted to specific environmental and climatic conditions is important for sustainable pest suppression in integrated management (IPM) programs. The objective is to report, for the first time, the occurrence of the Steinernema diaprepesi in Brazil. Steel mesh traps with Galleria mellonella Linnaeus (Lepidoptera: Pyralidae) larvae were buried in red latosol cultivated with Eucalyptus. Infective juveniles (IJs) were isolated from dead larvae and multiplied in healthy ones of this host to confirm its pathogenicity and to start a laboratory population from the strain found in the field. The DNA of the IJs was extracted and amplified using PCR technique with the universal primers D2A and D3B. The detection of S. diaprepesi is the first report of this nematode in Brazil, increasing the knowledge about its distribution in the world and the diversity of EPNs that must be considered as agents of biological pest control in the country.

Magic mushroom: all is not as it seems.

BACKGROUND: The late adverse effects of radiotherapy are caused by microvascular injury or depletion of differentiated cells. METHODS: Here we describe a clinical case of a late and unusual complication related to radiotherapy, in a patient with a history of squamous cell carcinoma of the anal canal. RESULTS: The patient presented with a large perianal vegetating lesion suspicious of local recurrence, however the biopsy of the lesion did not show malignancy. CONCLUSION: Fortunately, all is not as it seems, and what appeared as a suspected relapse turned out to be a benign reactive lesion, consequence of radiotherapy.

Development of native forest species of the Atlantic forest in soil contaminated with hormonal herbicides.

Hormonal herbicides, used in pastures, can suffer drift and reach forests. The sensitivity and potential phytoremediation of native species to herbicide residues should be evaluated. The objective of this study is to evaluate the initial development of native Atlantic Forest tree species in soil contaminated with hormonal herbicides. The experiment was conducted in a greenhouse in a 4 x 8 factorial scheme. The first factor had the control and the herbicide Tordon® in three doses (0.166, 0.333 and 0.666 L ha-1) and the second consisted of the forest species Anadenanthera colubrina (Vell.), Cassia ferruginea (Schrad.) Schrad. ex DC., Dalbergia villosa (Benth.) Benth., Machaerium nyctitans (Vell.) Benth., Machaerium opacum Vogel, Piptadenia gonoacantha (Mart.) JF Macbr., Senegalia polyphylla (DC.) Britton and Rose, Senna macranthera (DC Collad.) HS Irwin and Barnaby. The emergence, height, survival, emergence speed index, intoxication, root volume, stem diameter, root and shoot dry mass, leaf area and leaf numbers of the forest species were evaluated. The A. colubrina, D. villosa and M. opacum initial development was reduced by the herbicides 2.4-D plus picloram residues. S. macranthera and P. gonoacantha are tolerant to this mixture and, therefore, show potential for phytoremediation of degraded areas containing residues of these compounds.

Effects of the herbicide trifluralin in the initial development of Piptadenia gonoacantha (Fabales: Fabaceae).

Trifluralin, a pre-emergent herbicide, is widely used in Brazil in the weed grass management in restoration areas. The objective was to evaluate the tolerance of Piptadenia gonoacantha to trifluralin. The treatments had three trifluralin doses (445, 890, and 1335 g a.i. ha-1), applied in pre-sowing, as well as the control, without herbicide. Visual intoxication, seed germination, survival rate, emergence speed index (EMI), mean germination period, seedling height, and diameter, micromorphometric parameters of plant roots collected at 60 d after sowing, root length (RL) and volume, leaf area (LA), leaf numbers, root and shoot dry matter, and fluorescence of chlorophyll a at 30, 45, and 60 d after sowing were analyzed. Visual intoxication values above 50% were observed only with 1335 g a.i. ha-1. The herbicide did not affect seed germination, EMI, average germination period, seedling height, and diameter, root micromorphometric parameters, length, dry matter or root volume, and chlorophyll a fluorescence. The dose 1335 g a.i. ha-1 caused a reduction of 41.5% in survival, 50.3% in the LA, 36.7% in the number of leaves (LN), and 59.8% in the aerial dry mass of seedlings. The trifluralin presents potential for restoration programs of degraded areas with this forest species.

Oat, Wheat, and Sorghum Genotype Reactions to Meloidogyne incognita and Meloidogyne javanica.

Meloidogyne spp. are the most economically important species of plant-pathogenic nematodes. Plant resistance and crop rotation are the main nematode management methods. Thus, the objective was to evaluate the resistance of seven wheat genotypes, five oat genotypes, ten sorghum hybrids, and three sorghum-sudangrass genotypes to Meloidogyne incognita and Meloidogyne javanica. The crops were sowed in pots with an autoclaved substrate. A single plant/pot was left after thinning. The soil was infested with 5,000 eggs of the studied nematodes. Tomato (cv. Rutgers) plants were used as the standard for nematode susceptibility. The evaluations were conducted 60 d after inoculation. Gall and egg-mass indexes were obtained according to a 0-5 scale. Plants with a reproduction factor higher than 1.0 were classified as susceptible (S) and lower than 1.0 as resistant (R). Wheat and oat genotypes did not allow M. incognita and M. javanica reproduction, proving resistance to these organisms. Sorghum genotypes had different reactions to M. incognita and M. javanica. The tomato (cv. Rutgers) plants demonstrated the viability of the nematode inoculum for the three crops. The wheat and oat genotypes and the sorghum hybrids 'BRS-610', 'BRS-800', and '307.343' can be used in crop rotation systems for M. incognita and M. javanica management.

Transhepatic Transcatheter Pulmonary Valve Replacement.

Transcatheter pulmonary valve replacement (TPVR) is complicated in patients without adequate femoral or internal jugular vascular access. Transhepatic vascular access has been shown to be safe and effective across a spectrum of diagnostic and interventional procedures. Closure of the hepatic venous tract can be accomplished with a multitude of readily available vascular occlusion devices. The rates of major adverse events are low: 5% to 8% with hemoperitoneum and complete heart block are most significant. To our knowledge, this is the first report of using transhepatic access for TPVR; closure of the hepatic venous tract was achieved with an Amplatzer vascular plug type II.

Prognostic impact of thrombocytosis in gastric cancer-A retrospective study.

BACKGROUND: Solid tumors are a common cause of secondary thrombocytosis, which has been identified as a prognostic factor in various cancers. However, the impact of thrombocytosis on the prognosis of gastric cancer is not yet well defined. The aim of this study was to assess the prevalence and prognostic value of thrombocytosis in patients with gastric cancer. METHODS: This was a retrospective study of patients with gastric carcinoma treated surgically, with curative intent, in our hospital, Centro Hospitalar Vila Nova de Gaia/Espinho, between January 2009 and December 2019. Clinical files were consulted and clinicopathological characteristics were analyzed. RESULTS: In the present sample (n = 352), the prevalence of pretreatment thrombocytosis was 16.5%. Thrombocytosis was associated with more advanced T stage, greater number of metastatic nodes, and more frequent lymphatic and venous permeation. The presence of thrombocytosis had a negative impact on disease-free survival (hazard ratio [HR] 3.54, 95% confidence interval [CI] 2.35-5.33, P < .001) and overall survival (HR 4.45, 95% CI 2.95-6.71, P < .001). CONCLUSIONS: The presence of pretreatment thrombocytosis had a negative impact on overall survival and disease-free survival and thus could be used as an independent prognostic factor.

Midgut Cell Damage and Oxidative Stress in Partamona helleri (Hymenoptera: Apidae) Workers Caused by the Insecticide Lambda-Cyhalothrin.

The stingless bee Partamona helleri plays a role in pollinating both native and cultivated plants in the Neotropics. However, its populations can be reduced by the pyrethroid insecticide lambda-cyhalothrin. This compound may cross the intestinal barrier and circulate through the hemolymph, affecting various non-target bee organs. The aim of the present study was to assess the extent of cellular damage in the midgut and the resulting oxidative stress caused by lambda-cyhalothrin in P. helleri workers. Bees were orally exposed to lambda-cyhalothrin. The lethal concentration at which 50% of the bees died (LC50) was 0.043 mg a.i. L-1. The P. helleri workers were fed this concentration of lambda-cyhalothrin and their midguts were evaluated. The results revealed signs of damage in the midgut epithelium, including pyknotic nuclei, cytoplasm vacuolization, changes in the striated border, and the release of cell fragments, indicating that the midgut was compromised. Furthermore, the ingestion of lambda-cyhalothrin led to an increase in the activity of the detoxification enzyme superoxide dismutase and the levels of the NO2/NO3 markers, indicating oxidative stress. Conversely, the activities of the catalase and glutathione S-transferase enzymes decreased, supporting the occurrence of oxidative stress. In conclusion, the ingestion of lambda-cyhalothrin by P. helleri workers resulted in damage to their midguts and induced oxidative stress.