Incidence and risk factors of bacterial sepsis and invasive fungal infection in neonates and infants requiring major surgery: an Italian multicentre prospective study.

BACKGROUND: Limited data are currently available on the incidence rates and risk factors for bacterial sepsis and invasive fungal infections (IFIs) among neonates and infants undergoing major surgery. AIM: To assess the incidence of bacterial sepsis and IFI, fungal colonization, risk factors for sepsis, and mortality in neonates and infants aged <3 months undergoing major surgery. METHODS: A multicentre prospective study was conducted involving 13 level-3 neonatal intensive care units in Italy, enrolling all infants aged ≤3 months undergoing major surgery. FINDINGS: From 2018 to 2021, 541 patients were enrolled. During hospitalization, 248 patients had a bacterial infection, and 23 patients had a fungal infection. Eighty-four patients were colonized by fungal strains. Overall, in-hospital mortality was 2.8%, but this was higher in infected than in uninfected infants (P = 0.034). In multivariate analysis, antibiotic exposure before surgery, ultrasound-guided or surgical placement of vascular catheters, vascular catheterization duration, and gestational age ≤28 weeks were all associated with bacterial sepsis. The risk of IFI was markedly higher in colonized infants (odds ratio (OR): 8.20; P < 0.001) and was linearly associated with the duration of vascular catheterization. Fungal colonization in infants with abdominal surgery increased the probability of IFI 11-fold (OR: 11.1; P < 0.001). CONCLUSION: Preventive strategies such as early removal of vascular catheters and the fluconazole prophylaxis should be considered to prevent bacterial and fungal sepsis in infants undergoing abdominal surgery, and even more so in those with fungal colonization.

Efficacy of continuous versus intermittent administration of nanoformulated benznidazole during the chronic phase of Trypanosoma cruzi Nicaragua infection in mice.

BACKGROUND: Benznidazole and nifurtimox are effective drugs used to treat Chagas' disease; however, their administration in patients in the chronic phase of the disease is still limited, mainly due to their limited efficacy in the later chronic stage of the disease and to the adverse effects related to these drugs. OBJECTIVES: To evaluate the effect of low doses of nanoformulated benznidazole using a chronic model of Trypanosoma cruzi Nicaragua infection in C57BL/6J mice. METHODS: Nanoformulations were administered in two different schemes: one daily dose for 30 days or one dose every 7 days, 13 times. RESULTS: Both treatment schemes showed promising outcomes, such as the elimination of parasitaemia, a reduction in the levels of T. cruzi-specific antibodies and a reduction in T. cruzi-specific IFN-γ-producing cells, as well as an improvement in electrocardiographic alterations and a reduction in inflammation and fibrosis in the heart compared with untreated T. cruzi-infected animals. These results were also compared with those from our previous work on benznidazole administration, which was shown to be effective in the same chronic model. CONCLUSIONS: In this experimental model, intermittently administered benznidazole nanoformulations were as effective as those administered continuously; however, the total dose administered in the intermittent scheme was lower, indicating a promising therapeutic approach to Chagas' disease.

Is the infectiousness of dogs naturally infected with Trypanosoma cruzi associated with poly-parasitism?

Interactions among different species of parasites co-infecting the same host could be synergistic or antagonistic. These interactions may modify both the frequency of infected hosts and their infectiousness, and therefore impact on transmission dynamics. This study determined the infectiousness of Trypanosoma cruzi-seropositive dogs (using xenodiagnosis) and their parasite load (quantified by qPCR), and tested the association between both variables and the presence of concomitant endoparasites. A cross-sectional serosurvey conducted in eight rural villages from Pampa del Indio and neighboring municipalities (northeastern Argentina) detected 32 T. cruzi-seropositive dogs out of 217 individuals examined for infection. Both the infectiousness to the vector Triatoma infestans and parasite load of T. cruzi-seropositive dogs examined were heterogeneous. A statistically significant, nine-fold higher mean infectiousness was registered in T. cruzi-seropositive dogs co-infected with Ancylostoma caninum and a trematode than in T. cruzi-seropositive dogs without these infections. The median parasite load of T. cruzi was also significantly higher in dogs co-infected with these helminths. An opposite trend was observed in T. cruzi-seropositive dogs that were serologically positive to Toxoplasma gondii or Neospora caninum relative to dogs seronegative for these parasites. Using multiple logistic regression analysis with random effects, we found a positive and significant association between the infectiousness of T. cruzi-seropositive dogs and co-infections with A. caninum and a trematode. Our results suggest that co-infections may be a modifier of host infectiousness in dogs naturally infected with T. cruzi.

Does injection of plasma rich in growth factors after temporomandibular joint arthroscopy improve outcomes in patients with Wilkes stage IV internal derangement? A randomized prospective clinical study.

The aim of this study was to evaluate the efficacy of injection of plasma rich in growth factors (PRGF) after temporomandibular joint (TMJ) arthroscopy in patients with Wilkes stage IV internal derangement. Ninety-two patients were randomized to two experimental groups: group A (42 joints) received injections of PRGF, group B (50 joints) received saline injections. Pain intensity on a visual analogue scale (VAS) and maximum mouth opening (MMO, mm) were measured before and after surgery and compared by analysis of variance (ANOVA). The mean age of patients was 35.8 years (range 17-67 years); 86 were female. Significant reductions in pain were noted in both groups after surgery: VAS 7.9 preoperative and 1.4 at 24 months postoperative. Significantly better clinical results were achieved in group A than in group B only at 6 and 12 months postoperative; no significant difference was noted at 18 or 24 months after the surgical intervention. MMO increased after surgery in both groups: 26.2mm preoperative and 36.8mm at 24 months postoperative. No significant differences in MMO were found when the two groups of patients were compared. In conclusion, the injection of PRGF does not add any significant improvement to clinical outcomes at 2 years after surgery in patients with advanced internal derangement of the TMJ.

High levels of Trypanosoma cruzi DNA determined by qPCR and infectiousness to Triatoma infestans support dogs and cats are major sources of parasites for domestic transmission.

The competence of reservoir hosts of vector-borne pathogens is directly linked to its capacity to infect the vector. Domestic dogs and cats are major domestic reservoir hosts of Trypanosoma cruzi, and exhibit a much higher infectiousness to triatomines than seropositive humans. We quantified the concentration of T. cruzi DNA in the peripheral blood of naturally-infected dogs and cats (a surrogate of intensity of parasitemia), and evaluated its association with infectiousness to the vector in a high-risk area of the Argentinean Chaco. To measure infectiousness, 44 infected dogs and 15 infected cats were each exposed to xenodiagnosis with 10-20 uninfected, laboratory-reared Triatoma infestans that blood-fed to repletion and were later individually examined for infection by optical microscopy. Parasite DNA concentration (expressed as equivalent amounts of parasite DNA per mL, Pe/mL) was estimated by real-time PCR amplification of the nuclear satellite DNA. Infectiousness increased steeply with parasite DNA concentration both in dogs and cats. Neither the median parasite load nor the mean infectiousness differed significantly between dogs (8.1Pe/mL and 48%) and cats (9.7Pe/mL and 44%), respectively. The infectiousness of dogs was positively and significantly associated with parasite load and an index of the host's body condition, but not with dog's age, parasite discrete typing unit and exposure to infected bugs in a random-effects multiple logistic regression model. Real-time PCR was more sensitive and less time-consuming than xenodiagnosis, and in conjunction with the body condition index, may be used to identify highly infectious hosts and implement novel control strategies.

An unusual intraparotid foreign body simulating a tumour: shrapnel from the Spanish Civil War.

A foreign body lodged for decades in the parotid gland, entering through the oral cavity or the skin, is extremely rare. Even less common is the clinical presentation of a foreign body lodged in the parotid gland simulating a tumour. The authors report the finding of a fragment of shrapnel lodged in the parotid gland for 63 years. The case is unusual owing to the rare clinical presentation, the length of time between the injury and the occurrence of symptoms and the associated mandibular osteolysis in the panoramic radiograph. Initial diagnoses considered were a tumour emerging in the parotid gland, a large odontogenic cyst or an odontogenic tumour with soft tissue extension. Sometimes neither fine needle aspiration nor radiology is capable of providing an accurate diagnosis before surgery.

Orthognathic surgery in pycnodysostosis: a case report.

Pycnodysostosis is an extremely rare genetic osteosclerosis caused by cathepsin K deficiency. It is a human autosomal recessive genetic disorder characterized mainly by osteosclerosis of the skeleton due to decreased bone turnover. It is characterized by short stature, brachycephaly, short and stubby fingers, open cranial sutures and fontanelle, and diffuse osteosclerosis. Multiple fractures of the long bones and osteomyelitis of the jaw are frequent complications. The authors describe an 18-year-old girl with a clinical and radiological diagnosis of pycnodysostosis and the ortho-surgical treatment undertaken. Bimaxillary orthognathic surgery was carried out using rigid fixation and bone grafts. The authors recommend bimaxillary orthognathic surgery as a choice for treating the dentofacial deformities of pycnodysostosis, emphasizing the good and stable results obtained in terms of facial aesthetics and occlusion.

Angiolipoma in head and neck: report of two cases and review of the literature.

Angiolipomas are either encapsulated or non-encapsulated fatty tumours. They are distinguished from other lipomas by the excessive degree of vascular proliferation and because they are mixed with mature adipocytes. They commonly occur in the trunk and extremities and are rare in the maxillofacial area. Only 36 cases in the head and neck have been reported in the literature. The authors report the first non-infiltrating intramasseterine angiolipoma, and a case of non-infiltrating angiolipoma of the cheek. These tumours appear as homogenous low-density areas on CT with no contrast enhancement. MRI gives better tumour delineation and clear definition of the location and longitudinal extent of the mass. Histopathology demonstrates mature adipose tissue and the proliferation of numerous small branching blood vessels. Management of angiolipomas requires complete surgical excision.

Herida por asta de toro en el área maxilofacial: revisión de la literatura y presentación de un caso / Maxillofacial injury by bull goring: literature review and case report

Introducción. Las heridas por asta de toro son relativamente frecuentesen España y países iberoamericanos, donde los espectáculos con estos animalesson habituales. Dichas heridas presentan unas características específicas que las diferenciande cualquier otro tipo de heridas.Material y método. Se presenta el caso de un paciente varón de 18 años, remitido alHospital 12 de Octubre por el SAMUR tras sufrir una cornada en la región cérvicofacialdurante los encierros de San Sebastián de los Reyes en el verano de 2005. Elpaciente presenta una herida inciso-contusa y anfractuosa desde la región supraclavicularizquierda hasta la comisura labial ipsilateral, con fractura mandibularconminuta a nivel de ángulo izquierdo y cuerpo derecho, fractura dentoalveolar depiezas 1.3 a 2.3, y laceración severa de la musculatura lingual y suelo de boca.Discusión. La mayor parte de los politraumatizados por asta de toro son varones, conuna edad media de 30. Las victimas suelen ser participantes espontáneos, aficionadosa los eventos taurinos y no toreros profesionales.Si bien las heridas por asta de toro pueden producirse en cualquier parte del cuerpo,la localización más frecuente en todas las series revisadas es el miembro inferior. Laregión cérvicofacial es una de las menos afectadas en todas las series. Todos los autorescoinciden en la baja incidencia de heridas pese a la gran cantidad de aficionadosy curiosos atraídos y por esta modalidad de festejos taurinos. Por todas las característicasparticulares del mecanismo de lesión, el tratamiento debe ser urgente y deberealizarse un traslado lo más rápidamente posible a un hospital. Todos los autoresestán de acuerdo en que inicialmente el paciente con una lesión por asta de torodebe ser considerado un paciente politraumatizado y tratado como tal...AU)

Introduction. Injuries produced by bull goring are relativelycommon in Spain and South American countries, where bullfightsare scheduled regularly. These wounds have specific characteristicsthat differentiate them from any other type of wounds.Material and methods. In the summer of 2005, an 18-year-oldmale patient was brought to the Hospital 12 de Octubre byemergency services after being gored in the cervicofacial regionduring the running of the bulls in San Sebastián de los Reyes. Thepatient had an anfractuous, penetrating and blunt wound extendingfrom the left supraclavicular region to the left lip commissure,comminuted fracture of the left mandibular angle and rightmandibular body, dentoalveolar fractures of pieces 1.3 to 2.3, andsevere laceration of the lingual musculature and mouth floor.Discussion. Most patients who suffer multiple injuries as a result ofbull goring are men, with a mean age of 30 years. Victims usuallyare spontaneous participants, bullfighting fans rather thanprofessional bullfighters. The wounds produced by the horns of thebull may be located anywhere in the body, but the most frequentlocation in all the series reviewed was the lower limb. The cervicofacialregion is one of less frequently affected regions in all the series. Allauthors agree that these injuries have a low incidence despite thehuge number of bullfight fans and curious spectators who areattracted by bullfight events. Emergency treatment is requiredbecause of the particular characteristics of the mechanism of injury.The patient should be taken as rapidly as possible to a hospital.Authors generally agree that any patient who has been gored by abull must be considered initially, for purposes of management, asa patient with multiple injuries...(AU)

Anti-Trypanosoma cruzi effects of cyclosporin A derivatives: possible role of a P-glycoprotein and parasite cyclophilins.

Cyclophilins are target molecules for cyclosporin A (CsA), an immunosuppressive antimicrobial drug. We have previously reported the in vitro anti-Trypanosoma cruzi activity of H-7-94 and F-7-62 non-immunosuppressive CsA analogues. In this work, we continue the study of the parasiticidal effect of H-7-94 and F-7-62 CsA analogues in vitro and in vivo and we analyse 3 new CsA derivatives: MeIle-4-CsA (NIM 811), MeVal-4-CsA (MeVal-4) and D-MeAla-3-EtVal-4-CsA, (EtVal-4). The most efficient anti-T. cruzi effect was observed with H-7-94, F-7-62 and MeVal-4 CsA analogues evidenced as inhibition of epimastigote proliferation, trypomastigote penetration, intracellular amastigote development and in vivo T. cruzi infection. This trypanocidal activity could be due to inhibition of the peptidyl prolyl cis-trans isomerase activity on the T. cruzi recombinant cyclophilins tested. Furthermore, CsA and F-7-62 derivative inhibited the efflux of rhodamine 123 from T. cruzi epimastigotes, suggesting an interference with a P-glycoprotein activity. Moreover, H-7-94 and F-7-62 CsA analogues were not toxic as shown by cell viability and by aminopyrine-N-demethylase activity on mammalian cells. Our results show that H-7-94, F-7-62 and MeVal-4 CsA analogues expressed the highest inhibiting effects on T. cruzi, being promissory parasiticidal drugs worthy of further studies.

Analysis of the Trypanosoma cruzi cyclophilin gene family and identification of Cyclosporin A binding proteins.

The Trypanosoma cruzi cyclophilin gene family comprises 15 paralogues whose nominal masses vary from 19 to 110 kDa, namely TcCyP19, TcCyP20, TcCyP21, TcCyP22, TcCyP24, TcCyP25, TcCyP26, TcCyP28, TcCyP29, TcCyP30, TcCyP34, TcCyP35, TcCyP40, TcCyP42 and TcCyP110. Under the conditions used, only some of the T. cruzi cyclophilin paralogue products could be isolated by affinity chromatography. The 15 paralogues were aligned with 495 cyclophilins from diverse organisms. Analyses of clusters formed by the T. cruzi cyclophilins with others encoded in various genomes revealed that 8 of them (TcCyP19, TcCyP21, TcCyP22, TcCyP24, TcCyP35, TcCyP40, TcCyP42 and TcCyP110) have orthologues in many different genomes whereas the other 7 display less-defined patterns of their sequence attributes and their classification to a specific group of cyclophilin's orthologues remains uncertain. Seven epimastigote cDNA clones encoding cyclophilin isoforms were further studied. These genes were found dispersed throughout the genome of the parasite. Amastigote and trypomastigote mRNAs encoding these 7 genes were also detected. We isolated 4 cyclosporin A-binding proteins in T. cruzi epimastigote extracts, which were identified by mass spectrometry as TcCyP19, TcCyP22, TcCyP28 and TcCyP40. Cyclosporin A-binding to these cyclophilins might be of importance to the mechanism of action of Cyclosporin A and its non-immunosuppressive analogues, whose trypanocidal effects were previously reported, and therefore, of potential interest in the chemotherapy of Chagas' disease.

Weight history from birth through childhood and youth in relation to adult lung function, in Danish juvenile obese and non-obese men.

OBJECTIVE: To investigate the associations of birth weight, body mass index (BMI) during childhood and youth, and current BMI with adult lung function. DESIGN: Population-based longitudinal study of juvenile obese and non-obese men, who were identified at draft board examination (age range: 19-27 y) and who participated in a follow-up examination in 1981-1983 (age range: 25-48 y). Birth weight, childhood weight and height measurements from 7 to 13 y of age were obtained from school health records. Current BMI and lung function were assessed at follow-up. SETTING: Copenhagen and adjacent regions, Denmark. SUBJECTS: In total, 193 juvenile obese men at draft board examination and 205 randomly selected nonobese controls from the same population. MAIN OUTCOME MEASURES: Lung function measured by forced expiratory volume in 1 s (FEV(1)) and forced vital capacity (FVC), adjusted for age and height. RESULTS: After adjusting for current BMI, smoking and education, birth weight was positively related to FEV(1), although only with borderline statistical significance. BMI at age 7 y was positively associated with both FEV(1) and FVC, whereas BMI at later ages in childhood and in youth was not associated with these measures. There was a strong negative linear relation between current BMI and lung function among those currently overweight and obese (BMI 25 kg/m(2)), whereas no association was seen in the non-obese (BMI <25 kg/m(2)). CONCLUSION: Our findings confirm the detrimental effect of high current BMI on adult lung function, and further suggest that early childhood growth has a protective influence.

Characterisation of a cyclophilin isoform in Trypanosoma cruzi.

The immunosuppressive drug cyclosporin A (CsA) has shown antiparasitic activity against several protozoans and helminths, when complexed to proteins called cyclophilins (CyPs). In this paper, the molecular characterisation of one member of the CyP family in Trypanosoma cruzi is reported. TcCyP19 gene proved to be highly conserved compared to CyPs from other organisms and was highly homologous to a Trypanosoma brucei brucei CyPA. This gene was expressed in Escherichia coli and the purified recombinant protein exhibited a peptidyl prolyl cis-trans isomerase activity that was inhibited by CsA (IC(50) = 18.4 + /-0.8 nM). The TcCyP19 gene was located on two chromosomal bands in T. cruzi CL Brener clone.

[Trypanosoma cruzi genome: transcriptional mapping and karyotype correlation; molecular characterization of a surface antigen from the Tc13 family]. / Genoma del Trypanosoma cruzi. Correlación entre el mapa transcripcional y el cariotipo caracterización molecular de un antígeno de superficie de la familia TC13.

We describe herein the genome mapping of Trypanosoma cruzi, the etiological agent of Chagas' disease, by hybridization of a cosmid library gridded in high density filters with cDNA from an epimastigote expression library as probes. We also show the correlation of some cosmid contigs with parasite chromosomal bands. With libraries from the T. cruzi Genome Project we have characterized a new member of the Tc13 family belonging to the superfamily of trypomastigote surface antigens. Starting with a Tulahuén strain (Tul 2 stock) clone, homologous to these antigens, we have sequenced and characterized the complete gene in the CL Strain (CL Brener clone). We have also found homologies with different ESTs which characterization would lead to further knowledge of this antigen family.