Hemoglobin Is a Vital Determinant of Arterial Oxygen Content in Hypoxemic Patients with Pulmonary Arteriovenous Malformations.

RATIONALE: Arterial partial pressure of oxygen (PaO2), and oxygen saturation (SaO2) are commonly measured in respiratory practice, but arterial oxygen content (CaO2) refers to the volume of oxygen delivered to the tissues per unit blood volume. CaO2 is calculated from SaO2 and the hemoglobin concentration in blood, recognizing that each gram of hemoglobin can transport approximately 1.34mls of oxygen when fully saturated. OBJECTIVES: To prospectively evaluate serial changes in CaO2 in man, incorporating and excluding dynamic changes to oxygenation and hemoglobin parameters that may occur during life. METHODS: A cohort of 497 consecutive patients at risk of both hypoxemia and anemia were recruited. The patients had radiologically-proven pulmonary arteriovenous malformations (PAVMs) which result in hypoxemia due to right-to-left shunting, and concurrent hereditary hemorrhagic telangiectasia (HHT) which placed them at risk of iron deficiency anemia due to recurrent hemorrhagic iron losses. Presentation SaO2 (breathing room air, by pulse oximetry), hemoglobin, red cell and iron indices were measured, and CaO2 calculated by SaO2*hemoglobin*1.34mls/gram. Serial measurements were evaluated in 100 cases spanning up to 32.1 (median 10.5) years. RESULTS: Presentation CaO2 ranged from 7.6-27.5 (median 17.6) mls/dL. CaO2 did not change appreciably across the SaO2 quartiles. In contrast, hemoglobin ranged from 5.9-21.8g/dL (median 14.1g/dL), with a linear increase in CaO2 across hemoglobin quartiles. Following PAVM embolization and an immediate increase in SaO2, hemoglobin fell and CaO2 was unchanged 1.6-12 (median 4) months later. When hemoglobin fell due to iron deficiency, there was no change in SaO2. Similarly, when hemoglobin rose after iron treatment, there was no change in SaO2, and the expected CaO2 increment was observed. These relationships were not evident during pregnancy when hemoglobin fell, and PAVMs usually deteriorated: In pregnancy SaO2 commonly increased, and serial CaO2 values (incorporating hemodilution/anemia) more accurately reflected deteriorating PAVM status. An apparent fall in CaO2 with age in females was attributable to the development of iron deficiency. There was an unexplained increase in CaO2 with age in males in follow up after embolization. CONCLUSIONS: Hemoglobin/CaO2 should be further incorporated into oxygenation considerations. More attention should be given to modest changes in hemoglobin that substantially modify CaO2

In vivo assessment of gastrotomy closure with over-the-scope clips in an experimental model for varicocelectomy

BACKGROUND: Gastrotomy closure remains the major limiting factor for human translation of transgastric surgery; the over-the-scope clip (OTSC) system was proposed as a possibility for this purpose. Transgastric access is good for a pelvic approach, making varicocelectomy a possible indication for natural orifice transluminal endoscopic surgery (NOTES). OBJECTIVE: To evaluate the reliability of the OTSC system in vivo after transgastric testicular vessel ligation (varicocelectomy model). DESIGN: There were 3 experimental groups (5 animals in each): groups 1 and 3, gastrotomy dilation up to 18 mm, surgery was performed with a double-channel endoscope; group 2, gastrotomy dilation up to 13 mm, surgery was performed with a single-channel endoscope. SETTING: Surgical Sciences Research Domain, Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal. INTERVENTIONS: Bilateral testicular vessel ligation by transgastric access. Gastrotomy closed with the largest version of OTSC system (12 mm): a single clip in groups 1 and 2, and 2 clips in group 3. Animals were monitored for 2 weeks, killed, and submitted for necropsy. MAIN OUTCOME MEASUREMENTS: Adequacy of closure and healing after the use of the OTSC system. Statistical analysis. RESULTS: Vessel ligation was easily achieved in all groups. Although differences in the complication rate did not reach statistical significance (P = .099), there was a clear tendency for a better prognosis in groups 2 and 3 than group 1. In fact, only 2 animals from group 1 had complications related to incomplete gastrotomy closure. LIMITATIONS: Small number of animals per group; nonrandomized study. CONCLUSIONS: The OTSC system was shown to be easy and efficient for gastrotomy closure in a survival experimental model of varicocelectomy, when correctly matching the gastrotomy size with the clip size and/or number

Third-generation cholecystectomy by natural orifices: transgastric and transvesical combined approach (with video)

BACKGROUND:An isolated transgastric port has some limitations in performing transluminal endoscopic cholecystectomy. However, transvesical access to the peritoneal cavity has recently been reported to be feasible and safe.OBJECTIVE:To assess the feasibility and the technical benefits of transgastric and transvesical combined approach to overcome the limitations of isolated transgastric ports.DESIGN:We created a transgastric and transvesical combined approach to perform cholecystectomy in 7 consecutive anesthetized female pigs. The transgastric access was achieved after perforation and dilation of the gastric wall with a needle knife and with a balloon, respectively. Under cystoscopic control, an ureteral catheter, a guidewire, and a dilator of the ureteral sheath were used to place a transvesical 5-mm overtube into the peritoneal cavity. By using a gastroscope positioned transgastrically and a ureteroscope positioned transvesically, we carried out cholecystectomy in all animals.RESULTS:Establishment of transvesical and transgastric accesses took place without complications. Under a carbon dioxide pneumoperitoneum controlled by the transvesical port, gallbladder identification, cystic duct, and artery exposure were easily achieved in all cases. Transvesical gallbladder grasping and manipulation proved to be particularly valuable to enhance gastroscope-guided dissection. With the exclusion of 2 cases where mild liver-surface hemorrhage and bile leak secondary to the sliding of cystic clips occurred, all remaining cholecystectomies were carried out without incidents.LIMITATIONS:Once closure of the gastric hole proved to be unreliable when using endoclips, the animals were euthanized; necropsy was performed immediately after the surgical procedure.CONCLUSIONS:A transgastric and transvesical combined approach is feasible, and it was particularly useful to perform a cholecystectomy through exclusive natural orifices

TERTp mutations and p53 expression in head and neck cutaneous basal cell carcinomas with different aggressive features

Cutaneous basal cell carcinoma (cBCC) is an economic burden to health services, due to its great morbidity and increasing incidence in old people. Infiltrative cBCCs and cBCCs with micronodular pattern are considered as more aggressive. The role of p53 expression and TERTp mutation on cBCC behavior remains to be clarified. We aimed to assess TERTp mutations and p53 expression in relation to the cBCC histological subtype in a cohort of patients referred to an ENT Department of a tertiary Hospital of Northern Portugal. We performed a retrospective clinicopathological and histological review of the head and neck cBCCs followed-up at the otorhinolaryngology department of Trás-os-Montes e Alto Douro hospital (January 2007–June 2018). We assessed TERTp mutations in 142 cBCCs and p53 protein expression, through immunohistochemistry, in 157 cBCCs. We detected TERTp mutations in 43.7% of cBCCs and p53 overexpression in 60.5% of cBCCs. We spotted association of p53 overexpression and TERTp mutation with necrosis. In the infitrative-growth pattern cBCCs, there was no significant association with the clinical and histological features evaluated, except for necrosis. In the indolent-growth cBCCs, we identified a significant association of TERTp mutation status with female sex, necrosis, multiple cBCCs, and p53 positive expression. Our results suggest that TERTp mutation may be useful to identify more aggressive features in the indolent-growth pattern cBCCs (nodular and superficial subtypes). Further studies with larger cohorts are warranted to clarify the relevance of TERTp mutation in cBCCs.This study was supported by FCT, the Portuguese Foundation for Science and Technology through a Ph.D. Grant to SM (SFRH/BD/137802/2018). This work was financed by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalization (POCI), Portugal 2020, and by Portuguese funds through FCT-Fundação para a Ciência e a Tecnolo-gia/Ministério da Ciência, Tecnologia e Inovação in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274). Additional funding by the European Regional Development Fund (ERDF) through the Operational Programme for Competitiveness and Internationalization—COMPETE2020, and Portuguese national funds via FCT, under project POCI-01-0145-FEDER-016390: CANCEL STEM and from the FCT, under the project POCI-01-0145-FEDER-031438: The other faces of telomerase: Looking beyond tumour immortalization (PDTC/MED-ONC/31438/2017)

DENTES DUPLOS: A IMPORTÂNCIA DO DIAGNÓSTICO PRECOCE

Introdução: Dentes duplos são anomalias da formação dentária decorrentes da união de dois germes dentários (fusão) ou da tentativa de divisão destes (geminação). A fusão pode ocorrer entre dois dentes normais ou entre um dente normal e outro supranumerário, é mais frequente na dentição decídua, sendo mais observada em incisivos e caninos, com maior frequência nos incisivos inferiores

Mass spectrometry imaging identifies palmitoylcarnitine as an immunological mediator during Salmonella Typhimurium infection

Salmonella Typhimurium causes a self-limiting gastroenteritis that may lead to systemic disease. Bacteria invade the small intestine, crossing the intestinal epithelium from where they are transported to the mesenteric lymph nodes (MLNs) within migrating immune cells. MLNs are an important site at which the innate and adaptive immune responses converge but their architecture and function is severely disrupted during S. Typhimurium infection. To further understand host-pathogen interactions at this site, we used mass spectrometry imaging (MSI) to analyse MLN tissue from a murine model of S. Typhimurium infection. A molecule, identified as palmitoylcarnitine (PalC), was of particular interest due to its high abundance at loci of S. Typhimurium infection and MLN disruption. High levels of PalC localised to sites within the MLNs where B and T cells were absent and where the perimeter of CD169+ sub capsular sinus macrophages was disrupted. MLN cells cultured ex vivo and treated with PalC had reduced CD4+CD25+ T cells and an increased number of B220+CD19+ B cells. The reduction in CD4+CD25+ T cells was likely due to apoptosis driven by increased caspase-3/7 activity. These data indicate that PalC significantly alters the host response in the MLNs, acting as a decisive factor in infection outcome

The MHC Gene Region of Murine Hosts Influences the Differential Tissue Tropism of Infecting Trypanosoma cruzi Strains

We have previously demonstrated that both parasite genetic variability and host genetic background were important in determining the differential tissue distribution of the Col1.7G2 and JG T. cruzi monoclonal strains after artificial infections in mice. We observed that the JG strain was most prevalent in hearts of mouse lineages with the MHC haplotype H-2d (BALB/c and DBA2), while Col1.7G2 was predominant in hearts from C57BL/6 mice, which have the H-2b haplotype. To assess whether the MHC gene region indeed influenced tissue tropism of T. cruzi, we used the same two parasite strains to infect C57BL/6 (H-2b) and C57BLKS/J (H-2d) mice; the latter strain results from the introgression of DBA2 MHC region into the C57BL/6 background. We also performed ex vivo infections of cardiac explants from four congenic mice lineages with the H-2b and H-2d haplotypes arranged in two different genetic backgrounds: C57BLKS/J (H-2d) versus C57BL/6 (H-2b) and BALB/c (H-2d) versus BALB/B10-H2b (H-2b). In agreement with our former observations, Col1.7G2 was predominant in hearts from C57BL/6 mice (H-2b), but we observed a clear predominance of the JG strain in hearts from C57BLKS/J animals (H-2d). In the ex vivo experiments Col1.7G2 also prevailed in explants from H-2b animals while no predominance of any of the strains was observed in H-2d mice explants, regardless of the genetic background. These observations clearly demonstrate that the MHC region influences the differential tissue distribution pattern of infecting T. cruzi strains, which by its turn may be in a human infection the determinant for the clinical forms of the Chagas disease

Ferritins: furnishing proteins with iron

Ferritins are a superfamily of iron oxidation, storage and mineralization proteins found throughout the animal, plant, and microbial kingdoms. The majority of ferritins consist of 24 subunits that individually fold into 4-α-helix bundles and assemble in a highly symmetric manner to form an approximately spherical protein coat around a central cavity into which an iron-containing mineral can be formed. Channels through the coat at inter-subunit contact points facilitate passage of iron ions to and from the central cavity, and intrasubunit catalytic sites, called ferroxidase centers, drive Fe2+ oxidation and O2 reduction. Though the different members of the superfamily share a common structure, there is often little amino acid sequence identity between them. Even where there is a high degree of sequence identity between two ferritins there can be major differences in how the proteins handle iron. In this review we describe some of the important structural features of ferritins and their mineralized iron cores and examine in detail how three selected ferritins oxidise Fe2+ in order to explore the mechanistic variations that exist amongst ferritins. We suggest that the mechanistic differences reflect differing evolutionary pressures on amino acid sequences, and that these differing pressures are a consequence of different primary functions for different ferritins