Cataract surgery is one of the most frequent surgeries in the world. It is a very safe procedure mostly performed under topical anesthesia in outpatients centers. Due to the growing lack of ...anesthesiologists, cataract surgeries are more frequently performed without an anesthesiologist present in the operating room. Although extremely rare, life-threatening complications may occur.
We report two cases of cataract surgery complicated by severe hypotension that required emergency resuscitation in the immediate postoperative period and hospitalization in intensive care unit. Anaphylactic shock was confirmed in the first case and suspected in the second.
Even though cataract surgery is a very safe procedure, it is essential to ensure the presence of an anesthesiologist to manage potential, though extremely rare, life-threatening complications such as anaphylactic reactions.
Recent data suggests the involvement of mitochondrial dynamics in cardiac ischemia/reperfusion (I/R) injuries. Whilst excessive mitochondrial fission has been described as detrimental, the role of ...fusion proteins in this context remains uncertain.
To investigate whether Opa1 (protein involved in mitochondrial inner-membrane fusion) deficiency affects I/R injuries.
We examined mice exhibiting Opa1delTTAG mutations (Opa1+/-), showing 70% Opa1 protein expression in the myocardium as compared to their wild-type (WT) littermates. Cardiac left-ventricular systolic function assessed by means of echocardiography was observed to be similar in 3-month-old WT and Opa1+/- mice. After subjection to I/R, infarct size was significantly greater in Opa1+/- than in WTs both in vivo (43.2±4.1% vs. 28.4±3.5%, respectively; p<0.01) and ex vivo (71.1±3.2% vs. 59.6±8.5%, respectively; p<0.05). No difference was observed in the expression of other main fission/fusion protein, oxidative phosphorylation, apoptotic markers, or mitochondrial permeability transition pore (mPTP) function. Analysis of calcium transients in isolated ventricular cardiomyocytes demonstrated a lower sarcoplasmic reticulum Ca2+ uptake, whereas cytosolic Ca2+ removal from the Na+/Ca2+ exchanger (NCX) was increased, whilst SERCA2a, phospholamban, and NCX protein expression levels were unaffected in Opa1+/- compared to WT mice. Simultaneous whole-cell patch-clamp recordings of mitochondrial Ca2+ movements and ventricular action potential (AP) showed impairment of dynamic mitochondrial Ca2+ uptake and a marked increase in the AP late repolarization phase in conjunction with greater occurrence of arrhythmia in Opa1+/- mice.
Opa1 deficiency was associated with increased sensitivity to I/R, imbalance in dynamic mitochondrial Ca2+ uptake, and subsequent increase in NCX activity.
Postoperative residual tumor is the major prognostic factor in ovarian cancer. The feasibility of complete cytoreductive surgery is assessed by laparoscopy. Our goal was to develop a predictive score ...prior to laparoscopy to evaluate the feasibility of complete cytoreductive surgery in patients with epithelial ovarian cancer.
We developed a score to predict incomplete cytoreductive surgery by performing multiple logistic regressions after bootstrap procedures on data from a retrospective cohort of 247 patients with advanced ovarian cancer. This score was validated on a different population of 45 patients with ovarian cancer.
Four criteria were independently associated with incomplete cytoreduction, confirmed by surgery: BMI ≥ 30 kg/m2 (adjusted odds ratio aOR, 3.07; 95% confidence interval 95% CI, 1.0-9.6), CA125 > 100 IU/L (aOR, 3.99; 95% CI, 1.6-10.1), diaphragmatic and/or omental carcinomatosis by CT-Scan (aOR, 5.82; 95% CI, 2.6-13.1), and positive parenchymal metastases by PET/CT (aOR, 3.59; 95% CI, 1.0-12.8). The 100-point score was based on these criteria. The area-under-the-curve of the score was 0.79 (95% CI, 0.73-0.86). In the validation group, no patient ranked in the high-risk group of incomplete cytoreductive surgery had a complete upfront cytoreductive surgery (95% CI 0-16). Three of 29 patients for whom primary complete cytoreduction was not possible were classified in the group at low risk of incomplete cytoreductive surgery (12%; 95% CI 4-27).
This pre-operative score may be useful for distinguishing which patients may have complete cytoreductive surgery from those who will receive neoadjuvant chemotherapy, while avoiding unnecessary laparoscopy.
Stromal interaction molecule 1 (STIM1) has been shown to control a calcium (Ca(2+)) influx pathway that emerges during the hypertrophic remodelling of cardiomyocytes. Our aim was to determine the ...interaction of Orai1 and Orai3 with STIM1 and their role in the constitutive store-independent and the store-operated, STIM1-dependent, Ca(2+) influx in cardiomyocytes.
We characterized the expression profile of Orai proteins and their interaction with STIM1 in both normal and hypertrophied adult rat ventricular cardiomyocytes. Orai1 and 3 protein levels were unaltered during the hypertrophic process and both proteins co-immunoprecipitated with STIM1. The level of STIM1 and Orai1 were significantly greater in the macromolecular complex precipitated by the Orai3 antibody in hypertrophied cardiomyocytes. We then used a non-viral method to deliver Cy3-tagged siRNAs in vivo to adult ventricular cardiomyocytes and silence Orai channel candidates. Cardiomyocytes were subsequently isolated then the voltage-independent, i.e. store-independent and store-operated Ca(2+) entries were measured on Fura-2 AM loaded Cy3-labelled and control isolated cardiomyocytes. The whole cell patch-clamp technique was used to measure Orai-mediated currents. Specific Orai1 and Orai3 knockdown established Orai3, but not Orai1, as the critical partner of STIM1 carrying these voltage-independent Ca(2+) entries in the adult hypertrophied cardiomyocytes. Orai3 also drove an arachidonic acid-activated inward current.
Cardiac Orai3 is the essential partner of STIM1 and drives voltage-independent Ca(2+) entries in adult cardiomyocytes. Arachidonic acid-activated currents, which are supported by Orai3, are present in adult cardiomyocytes and increased during hypertrophy.
Abstract The aim of these recommendations of the French National College of Gynaecologists and Obstetricians was to focus the surgeon's attention on those aspects which could allow him/her to ...prevent, or at least limit, the incidence of these serious complications, in the absence of a previous laparotomy or specific risk factors (obesity, gauntness, large pelvic mass or pregnancy), four widely evaluated techniques can be used in a first line approach (Grade B): blind trans-umbilical technique following creation of pneumoperitoneum with a needle, open laparoscopy (Hasson technique), left upper quadrant entry (pneumoperitoneum and insertion of the first trocar) and direct trans-umbilical trocar with no prior pneumoperitoneum. The currently existing trials do not allow one or another of these techniques to be preferred. Radially expanding insertion systems and optical trocars cannot be recommended as a first-line approach, as a consequence of their currently insufficient degree of evaluation (Grade C). Trans-umbilical (blind or open) laparoscopic entry in a slim woman must be associated with care, as a result of the proximity of the large vessels (Grade B). If a blind trans-umbilical insertion technique is decided upon, one option can be to insufflate into the left upper quadrant (professional consensus). In the case of a previous midline laparotomy, whatever the technique used, initial entry is recommended at a distance from the scars (Grade B). It is recommended to carry out micro-laparoscopy in the LUQ, because this is the most completely evaluated technique for this indication (Grade C). One option is to use open laparoscopy at a distance from the existing scars (professional consensus). During pregnancy, the insertion position of the first laparoscopic trocar will need to be adapted according to the volume of the uterus (Grade B). Starting from 14 WG, trans-umbilical Veress needle insufflation is contraindicated (Grade C). Two trocar insertion techniques are thus recommended: open laparoscopy (using the trans-umbilical or supra-umbilical routes, depending on the volume of the uterus) or micro-laparoscopy via the left upper quadrant (Grade C). After the second quarter of pregnancy, with laparoscopy the patient will need to be placed on a table inclined towards her left side, in order to minimize compression of the inferior vena cava (Grade B). In the case of laparoscopy during pregnancy, the insufflation pressure must be maintained at a maximum of 12 mm Hg (Grade B). After 24 WG, if laparoscopy is performed, it is recommended to apply open laparoscopy, above the level of the umbilicus (professional consensus). Patients must be informed of the risks inherent to the insertion of trocars during laparoscopy (vascular, bowel or bladder injury) (Grade B). The more benign the pathology requiring an operation, the more detailed the supplied information must be, including that concerning rare but serious complications (Grade B).
The cysteine protease caspase-1 (Casp-1) contributes to innate immunity through the assembly of NLRP3, NLRC4, AIM2, and NLRP6 inflammasomes. Here we ask whether caspase-1 activation plays a ...regulatory role in house dust mite (HDM)-induced experimental allergic airway inflammation. We report enhanced airway inflammation in caspase-1-deficient mice exposed to HDM with a marked eosinophil recruitment, increased expression of IL-4, IL-5, IL-13, as well as full-length and bioactive IL-33. Furthermore, mice deficient for NLRP3 failed to control eosinophil influx in the airways and displayed augmented Th2 cytokine and chemokine levels, suggesting that the NLPR3 inflammasome complex controls HDM-induced inflammation. IL-33 neutralization by administration of soluble ST2 receptor inhibited the enhanced allergic inflammation, while administration of recombinant IL-33 during challenge phase enhanced allergic inflammation in caspase-1-deficient mice. Therefore, we show that caspase-1, NLRP3, and ASC, but not NLRC4, contribute to the upregulation of allergic lung inflammation. Moreover, we cannot exclude an effect of caspase-11, because caspase-1-deficient mice are deficient for both caspases. Mechanistically, absence of caspase-1 is associated with increased expression of IL-33, uric acid, and spleen tyrosine kinase (Syk) production. This study highlights a critical role of caspase-1 activation and NLPR3/ASC inflammasome complex in the down-modulation of IL-33 in vivo and in vitro, thereby regulating Th2 response in HDM-induced allergic lung inflammation.
Protein kinase C (PKC) θ, a serine/threonine kinase, is involved in TH2 cell activation and proliferation. Type 2 innate lymphoid cells (ILC2s) resemble TH2 cells and produce the TH2 cytokines IL-5 ...and IL-13 but lack antigen-specific receptors. The mechanism by which PKC-θ drives innate immune cells to instruct TH2 responses in patients with allergic lung inflammation remains unknown.
We hypothesized that PKC-θ contributes to ILC2 activation and might be necessary for ILC2s to instruct the TH2 response.
PRKCQ gene expression was assessed in innate lymphoid cell subsets purified from human PBMCs and mouse lung ILC2s. ILC2 activation and eosinophil recruitment, TH2-related cytokine and chemokine production, lung histopathology, interferon regulatory factor 4 (IRF4) mRNA expression, and nuclear factor of activated T cells (NFAT1) protein expression were determined. Adoptive transfer of ILC2s from wild-type mice was performed in wild-type and PKC-θ–deficient (PKC-θ−/−) mice.
Here we report that PKC-θ is expressed in both human and mouse ILC2s. Mice lacking PKC-θ had reduced ILC2 numbers, TH2 cell numbers and activation, airway hyperresponsiveness, and expression of the transcription factors IRF4 and NFAT1. Importantly, adoptive transfer of ILC2s restored eosinophil influx and IL-4, IL-5 and IL-13 production in lung tissue, as well as TH2 cell activation. The pharmacologic PKC-θ inhibitor (Compound 20) administered during allergen challenge reduced ILC2 numbers and activation, as well as airway inflammation and IRF4 and NFAT1 expression.
Therefore our findings identify PKC-θ as a critical factor for ILC2 activation that contributes to TH2 cell differentiation, which is associated with IRF4 and NFAT1 expression in allergic lung inflammation.
Recent data suggests the involvement of mitochondrial dynamics in cardiac ischemia/reperfusion (I/R) injuries. Whilst excessive mitochondrial fission has been described as detrimental, the role of ...fusion proteins in this context remains uncertain. To investigate whether Opa1 (protein involved in mitochondrial inner-membrane fusion) deficiency affects I/R injuries. We examined mice exhibiting Opa1.sup.delTTAG mutations (Opa1.sup.+/- ), showing 70% Opa1 protein expression in the myocardium as compared to their wild-type (WT) littermates. Cardiac left-ventricular systolic function assessed by means of echocardiography was observed to be similar in 3-month-old WT and Opa1.sup.+/- mice. After subjection to I/R, infarct size was significantly greater in Opa1.sup.+/- than in WTs both in vivo (43.2#177;4.1% vs. 28.4#177;3.5%, respectively; p0.01) and ex vivo (71.1#177;3.2% vs. 59.6#177;8.5%, respectively; p0.05). No difference was observed in the expression of other main fission/fusion protein, oxidative phosphorylation, apoptotic markers, or mitochondrial permeability transition pore (mPTP) function. Analysis of calcium transients in isolated ventricular cardiomyocytes demonstrated a lower sarcoplasmic reticulum Ca.sup.2+ uptake, whereas cytosolic Ca.sup.2+ removal from the Na.sup.+ /Ca.sup.2+ exchanger (NCX) was increased, whilst SERCA2a, phospholamban, and NCX protein expression levels were unaffected in Opa1.sup.+/- compared to WT mice. Simultaneous whole-cell patch-clamp recordings of mitochondrial Ca.sup.2+ movements and ventricular action potential (AP) showed impairment of dynamic mitochondrial Ca.sup.2+ uptake and a marked increase in the AP late repolarization phase in conjunction with greater occurrence of arrhythmia in Opa1.sup.+/- mice. Opa1 deficiency was associated with increased sensitivity to I/R, imbalance in dynamic mitochondrial Ca.sup.2+ uptake, and subsequent increase in NCX activity.
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