Enhanced recovery after fetal spina bifida surgery: what is our global practice?

OBJECTIVE: Prenatal spina bifida closure results in improved outcomes for the child compared to postnatal surgery but is associated with significant maternal morbidity. Optimization of the perioperative care for women who underwent fetal spina bifida surgery could improve maternal and pregnancy outcomes. Enhanced Recovery After Surgery (ERAS) protocols are multimodal, evidence-based care plans that have been adopted for multiple surgical procedures to promote faster and better patient recovery and shorter hospitalization. This study aims to explore if fetal centers have implemented ERAS principles in this setting. Furthermore, we provide recommendations for the perioperative management of patients undergoing fetal spina bifida surgery. METHODS: Fifty-three fetal therapy centers offering prenatal surgery for open spina bifida were identified and invited to complete a digital questionnaire covering their pre-, intra- and postoperative management. An overall score was calculated per center based on the center's compliance with 20 key ERAS principles, extrapolated from ERAS guidelines for cesarean section, gynecologic oncology and colorectal surgery. Each item was scored 1 or 0 when the center did or did not comply with each principle, with a maximum score of 20. RESULTS: The questionnaire was completed by 46 centers in 17 countries (response rate 87%). Twenty-two centers (48%) exclusively perform open fetal surgery (laparotomy and hysterotomy), whereas 14 (30%) offer both open and fetoscopic procedures and 10 (22%) use fetoscopy only. The perioperative management of patients undergoing fetoscopic and open surgery was highly similar. The median ERAS score was 12 (mean 12.5, SD 2.4, range 8-17). Center compliance was the highest for the use of regional anesthesia (98%), avoidance of bowel preparation (96%), and thromboprophylaxis (96%), while the lowest compliance was achieved for preoperative carbohydrate loading (15%), postoperative nausea and vomiting prevention (33%), avoidance of overnight fasting (33%) and a 2-hour fasting period for clear fluids (20%). ERAS scores were similar in centers with a short (2-5 days), medium (6-10 days) and long (≥11 days) hospital stay (12.8 ± 2.4, 12.1 ± 2.0, and 10.3 ± 3.2, respectively, p=0.15). Furthermore, there was no significant association between ERAS score and surgical technique or center volume. CONCLUSION: The perioperative management of fetal spina bifida surgery is highly variable across fetal therapy centers worldwide. Standardizing protocols according to ERAS principles may improve patient recovery, reduce maternal morbidity, and shorten hospital stay after fetal spina bifida surgery. This article is protected by copyright. All rights reserved.

Level of polychlorinated biphenyls in tumor and blood serum of breast cancer patients and control subjects from Punjab, Pakistan.

The current study examined the level of Polychlorinated biphenyls (PCBs) in tumor and blood serum of female breast cancer patients and control individuals recruited from Punjab, Pakistan. Breast tumor and blood serum from 40 patients and only blood serum from ten control subjects were obtained and concentration of 32 PCB congeners was analyzed through Gas chromatography coupled with Mass spectrophotometry. Sociodemographic variables of the patients along with essential clinical and haematological parameters were taken as covariates. Tumor reflects the highest median (min-max) concentration (ng g-1 lw) of Æ©PCBs at 115.94 (0.05-17.75) followed by 16.53 (0.09-2.94) and 5.24 (0.01-0.59) in blood serum of cancer patients and control group respectively. Median concentrations (ng g-1 lw) of non-dioxine like Æ©PCBs were considerably higher at 83.04, 32.89 and 4.27 compared to 13.03 and 3.50 and 0.97 for dioxin like Æ©PCBs in tumor, serum of breast cancer patients and control subjects respectively. PCB-87 was most dominant congeners in tumor followed by PCB-170 and -82 whereas PCB-28 and -52 reflected greatest contribution in serum of breast cancer patients. Blood haemoglobin, potassium and chloride ions showed significant positive whereas body mass index reflect inverse relationship when regressed with Æ©PCBs in tumor. This pioneer study depicts elevated concentrations of PCBs in patients compared to control, reflecting potential positive association of PCBs with breast cancer which need further confirmation. We concluded that chronic exposure to PCBs might be associated with an increasing number of breast cancer incidences in developing countries like Pakistan, which should be further elucidated through detail in vitro and in vivo studies.

Correlation of fetal ventricular size and need for postnatal cerebrospinal fluid diversion surgery in open spina bifida.

OBJECTIVES: Open spina bifida is a common cause of hydrocephalus in the postnatal period. In-utero closure of the fetal spinal defect decreases the need for postnatal cerebrospinal fluid (CSF) diversion surgery. Good prenatal predictors of the need for postnatal CSF diversion surgery are currently lacking. In this study, we aimed to assess the association of fetal ventriculomegaly and its progression over the course of pregnancy with the rate of postnatal hydrocephalus requiring intervention. METHODS: In this retrospective study, fetuses with a prenatal diagnosis of open spina bifida were assessed longitudinally. Ventricular diameter, as well as other potential predictors of the need for postnatal CSF diversion surgery, were compared between fetuses undergoing prenatal closure and those undergoing postnatal repair. RESULTS: The diameter of the lateral ventricle increased significantly throughout gestation in both groups, but there was no difference in maximum ventricular diameter at first or last assessment between fetuses undergoing prenatal closure and those undergoing postnatal repair. There was no significant difference in the rate of progression of ventriculomegaly between the two groups, with a mean progression rate of 0.83 ± 0.5 mm/week in the prenatal-repair group and 0.6 ± 0.6 mm/week in the postnatal-repair group (P = 0.098). Fetal repair of open spina bifida was associated with a lower rate of postnatal CSF diversion surgery (P < 0.001). In all subjects, regardless of whether they had prenatal or postnatal surgery, the severity of ventriculomegaly at first and last assessments was associated independently with the need for postnatal CSF diversion surgery (P = 0.005 and P = 0.001, respectively), with a greater need for surgery in fetuses with larger ventricular size, even after controlling for gestational age at assessment. CONCLUSIONS: In fetuses with open spina bifida, fetal ventricular size increases regardless of whether spina bifida closure is performed prenatally or postnatally, but the need for CSF diversion surgery is significantly lower in those undergoing prenatal repair. Ventriculomegaly is associated independently with the need for postnatal CSF diversion in fetuses with open spina bifida, irrespective of timing of closure. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Short- and long-term outcome following thoracoamniotic shunting for fetal hydrothorax.

OBJECTIVES: To assess short- and long-term outcome in a cohort of fetuses diagnosed with hydrothorax (FHT) which underwent thoracoamniotic shunting in utero, and to examine the antenatal predictors of survival and of survival with normal neurodevelopmental outcome. METHODS: This was a retrospective analysis of 132 fetuses that underwent thoracoamniotic shunting at our center between 1991 and 2014. Data were extracted from hospital obstetric and relevant neonatal intensive care and neonatal developmental follow-up databases. Outcomes included survival to discharge and survival with normal neurodevelopmental outcome beyond 18 months. Information on malformations, syndromes and genetic abnormalities were obtained from antenatal, postnatal and pediatric hospital records or by parent report. We compared pregnancy characteristics among those who survived vs non-survivors and among those with normal neurodevelopmental outcome vs those who were abnormal or died. We explored whether there was a trend in survival over the study period. RESULTS: The mean gestational age at diagnosis of FHT was 25.6 weeks. The fetus was hydropic at diagnosis in 61% of cases, 69% had bilateral effusions and 55% had bilateral shunts inserted. Other diagnoses were present in 24% of cases, two-thirds of which were discovered only postnatally. There were 16 intrauterine and 30 neonatal deaths, with a 65% survival rate overall. The mean gestational age at delivery of liveborns was 35.4 (range, 26.9-41.6) weeks, and 88/116 (76%) were preterm (< 37 weeks). Of 87 liveborn at the treatment center, 75% experienced some respiratory and/or cardiovascular morbidity after birth, many with a lengthy hospital stay (mean, 36 (range, 1-249) days). Overall, 84% of survivors were developmentally normal beyond 18 months and outcomes were better when pleural effusions were isolated, 92% of these cases being neurodevelopmentally normal. There was no trend in survival or neurodevelopmental outcome over time. Despite the presence of FHT and neonatal respiratory issues, most (89%) of the 55 survivors with relevant follow-up had no long-term pulmonary complications. Gestational age at delivery was the only factor independently predictive of both survival and survival with normal neurodevelopmental outcome. CONCLUSIONS: FHT is associated with other pathologies in a quarter of cases and carries a significant risk of prematurity, mortality and neonatal morbidity. The outcome is good in survivors but is best in isolated cases. Predictors of outcome at diagnosis are poor. Future improvement in diagnostics at time of identification of FHT may help to identify those that would benefit most from thoracoamniotic shunting. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Awareness and Observance Rate of the Patients' Rights Charter in General Hospitals; The Perspectives of Iranian Patients.

One of the most important indicators for assessing the quality of healthcare is the evaluation of patients' rights status and the interaction between patients and the healthcare providers. The patient rights charter improves communication between patients and service providers and enhances the quality of healthcare. This is a descriptive-analytic study that was performed on 500 patients referred to 25 general hospitals supervised by Tehran University of Medical Sciences. In this study, the observance rate of the patient rights charter was considered and the patient rights charter in the samples were studied based on dependency type of hospitals. The patients' opinions showed that the observance rate of the patient rights charter in the hospitals was 60.7%. Observance rate of patients' rights charter according to the dependency type of hospitals (governmental - private - public - charity) in all clauses of the patient rights charter was statistically significant (p = 0.000). The findings of this study indicate that the majority of clauses in the patients' rights charter is observed in hospitals. In the field of observing of the patient rights charter, increasing patient's awareness about their rights is a priority. And in the next step, comprehensive and assured laws are needed to observe patients' rights in healthcare centers.

Protective effects of Smyrnium cordifolium boiss essential oil on pentylenetetrazol-induced seizures in mice: involvement of benzodiazepine and opioid antagonists.

Smyrnium cordifolium as a wild plant is used in traditional medicine in Iran for the treatment of anxiety and insomnia. The anticonvulsant effect of this plant has not been studied to date, therefore this study aimed to evaluate the anticonvulsant effects of its essential oil and curzerene on seizure. Essential oil of the Smyrnium cordifolium plant was prepared by the hydro-distillation method. Gas chromatography and gas chromatography-mass spectroscopy analysis of the essential oil revealed its main components. Anticonvulsant effects of Smyrnium cordifolium essential oil (SCEO) and curzerene were examined on mice using the pentylentetrazole model (PTZ). Flumazenil (2 mg/kg, i.p) and naloxone (5 mg/kg, i.p) were injected into the relevant groups of mice to realize the anticonvulsant mechanism of SCEO and curzerene, respectively. The main identified components of the plant were curzerene (65.26%), δ-Cadinene (14.39%) and γ-elemene (5.15%), which comprised approximately 85.28% of SCEO. The ED50 values of SCEO and curzerene in the PTZ model were 223±15 and 0.25±0.09 mg/kg, respectively. Curzerene at the dosage of 0.4 mg/kg prolonged the onset time of seizure and decreased the duration of seizure among treated group compared to the saline group. At the dosage of 0.4 mg/kg, seizure and mortality protection rates for the treated group were 100%. Flumazenil and naloxone could suppress the anticonvulsant effects of SCEO and curzerene. It seems that SCEO and curzerene are useful for the treatment of absence seizure and this effect may be related to their effects on GABAergic and opioid systems.

[Polymorphic variant of MnSOD A16V and risk of diabetic retinopathy].

Dabetic retinopatny Is the most common microvascular complication of diabetes and a leading cause of blindness in industrialized countries. Oxidative stress plays an important role in the development of microangiopathic complications in diabetes. Manganese superoxide dismutase (MnSOD) is a key mitochondrial antioxidant enzyme in the cellular defense against agents that induce oxidative stress. The aim of the present study was to assess whether the MnSODA16V (C47T) polymorphism is associated with Diabetic retinopathy in northern Iran. 140 patients with Diabetic retinopathy and 140 healthy individuals, aged 30 to 75 years old, participated in this study. For genotyping of the MnSOD A16V polymorphism, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used. The prevalence of genotype frequencies of AA, AV, VW in Diabetic retinopathy subject were 5.71, 71.43 and 22.86%, respectively while in controls were 21.43, 38.57 and 40%, respectively. Significantly increased frequency of AV genotype was observed in patients compared with controls (OR = 6.94, 95% CI = 2.98-16.20, P< 0.0001). In conclusion, it is suggested that the MnSOD A16V polymorphism may be associated with the risk of Diabetic retinopathy in northern Iran. However, larger population-based studies are needed for clarifying the relation between Diabetic retinopathy and MnSOD A16V polymorphism.

Management and outcomes of acute appendicitis in pregnancy-population-based study of over 7000 cases.

OBJECTIVE: To compare outcomes and management practices among pregnant and nonpregnant women with acute appendicitis. DESIGN: Population-based matched cohort study. SETTING: United States of America. SAMPLE: A total of 7114 women with appendicitis among 7,037,386 births. METHODS: Logistic regression analyses to calculate the odds ratio (OR) and corresponding 95% confidence intervals (95% CIs) for variables and outcomes of interest. MAIN OUTCOME MEASURES: Maternal morbidities associated with appendicitis; management practices for pregnant and age-matched nonpregnant women with appendicitis. RESULTS: There was an overall incidence of 101.1 cases of appendicitis per 100,000 births. Appendicitis was diagnosed in 35,570 nonpregnant women during the corresponding time frame. Peritonitis occurred in 20.3% of pregnant women with appendicitis, with an adjusted OR of 1.3 (95% CI 1.2-1.4) when compared with nonpregnant women with appendicitis. In pregnancy, there was an almost two-fold increase in sepsis and septic shock, transfusion, pneumonia, bowel obstruction, postoperative infection and length of stay >3 days. Whereas 5.8% of appendicitis cases among pregnant women were managed conservatively, they were associated with a considerably increased risk of shock, peritonitis and venous thromboembolism as compared to surgically managed cases. CONCLUSIONS: Compared with nonpregnant women, pregnant women with acute appendicitis have higher rates of adverse outcomes. Conservative management should be avoided given the serious risk of adverse outcomes in pregnancy.

Effect of composite resin contamination with powdered and unpowdered latex gloves on its shear bond strength to bovine dentin.

The aim of the present study was to evaluate the effect of composite resin contamination with powdered and unpowdered latex gloves on the shear bond strength of etch-and-rinse and two-step self-etch adhesive systems. Standard flat dentin surfaces were prepared on the facial aspect of 120 bovine incisors and randomly assigned into two (n=60) groups: group 1: Single Bond (SB), group 2: Clearfil SE Bond (CSE). Furthermore, each group was randomly subdivided into three (n=20) based on the type of composite contamination (without contamination, contamination with powdered latex gloves, and contamination with unpowdered latex gloves). The adhesives were applied and resin composite bonded to the dentin. After thermocycling, the specimens were subjected to a shear bond strength test. Two-way analysis of variance (ANOVA) and a post hoc Bonferroni test were used for statistical analysis. One-way ANOVA was used to compare shear bond strength values in each group. Statistical significance was set at p < 0.02. Two-way ANOVA showed that the shear bond strength was significantly influenced by the type of composite surface contamination (p=0.001). In the SB group there were no significant differences between different surface treatments (p=0.08). In the CSE group a significant difference was observed between the subgroup without contamination and the subgroup with powdered latex glove contamination (p=0.01); however, no significant differences were observed between the other subgroups.

Implications for psychedelic-assisted psychotherapy: functional magnetic resonance imaging study with psilocybin.

BACKGROUND: Psilocybin is a classic psychedelic drug that has a history of use in psychotherapy. One of the rationales for its use was that it aids emotional insight by lowering psychological defences. AIMS: To test the hypothesis that psilocybin facilitates access to personal memories and emotions by comparing subjective and neural responses to positive autobiographical memories under psilocybin and placebo. METHOD: Ten healthy participants received two functional magnetic resonance imaging scans (2 mg intravenous psilocybin v. intravenous saline), separated by approximately 7 days, during which they viewed two different sets of 15 positive autobiographical memory cues. Participants viewed each cue for 6 s and then closed their eyes for 16 s and imagined re-experiencing the event. Activations during this recollection period were compared with an equivalent period of eyes-closed rest. We split the recollection period into an early phase (first 8 s) and a late phase (last 8 s) for analysis. RESULTS: Robust activations to the memories were seen in limbic and striatal regions in the early phase and the medial prefrontal cortex in the late phase in both conditions (P<0.001, whole brain cluster correction), but there were additional visual and other sensory cortical activations in the late phase under psilocybin that were absent under placebo. Ratings of memory vividness and visual imagery were significantly higher after psilocybin (P<0.05) and there was a significant positive correlation between vividness and subjective well-being at follow-up (P<0.01). CONCLUSIONS: Evidence that psilocybin enhances autobiographical recollection implies that it may be useful in psychotherapy either as a tool to facilitate the recall of salient memories or to reverse negative cognitive biases.

Indoleamine 2,3-dioxygenase is expressed in the endometrium of cycling mice throughout the oestrous cycle.

Indoleamine 2,3-dioxygenase (IDO), an enzyme responsible for tryptophan catabolism, is thought to be required to prevent the rejection of the allogenic fetus by maternal T cells and to protect against intra- and extra-cellular pathogens. Consequently, we studied the expression of IDO in the endometrium of female Balb/c mice during the oestrous cycle. At each phase, the endometrium was peeled away and the relative expression of IDO mRNA was detected by semi-quantitative RT-PCR. The presence of IDO protein was confirmed in each phase by Western blotting and immunohistochemistry. Our results showed that IDO is expressed in the endometrium of cycling mice during all the phases of oestrous cycle. The expression of IDO was highest at the oestrus and lowest at the dioestrus. By means of Western blotting and immunohistochemistry, we obtained evidence that IDO protein is synthesised in the endometrium of cycling mice throughout the oestrous cycle. In accordance with RT-PCR results, IDO protein was predominant at the oestrus phase. IDO protein was mainly localised in the glandular and luminal epithelial cells. Our results support the concept of IDO providing a mechanism of innate immunity to protect from ascending infections of the female reproductive tract. In addition, considering the fact that mating only occurs during the oestrus phase, the high expression of IDO in this phase is likely to be a mechanism that induces immunological tolerance of the fetus.

Systemic lupus erythematosus in the Fars Province of Iran.

Clinical features of systemic lupus erythematosus (SLE) have been described from different geographical regions in the world. However, data from many Middle East countries, including Iran, are scarce. This study aims to demonstrate the demographic, clinical, and laboratory characteristics in Iranian patients with SLE. In this prospective study, all the patients referring to Shiraz educational hospitals (Nemazi-Hafez) with SLE (American College of Rheumatology criteria) during a 5-year period (2001 to 2006) were included. A complete history was taken; physical examination and routine hematological, serological, and immunological tests were done for each patient. There were 356 women and 54 men with an average age of 30.27 years at the onset of disease. Of the patients, 78% had hematological abnormalities, 65.5% had articular involvement, 54.5% had photosensitivity, and 60.5% had malar rash. Serositis occurred in 38% of patients of whom 12% had pericarditis and 26% had pleuritis. Nephritis was diagnosed in 48% of the cases and consisted always of glomerular nephritis. Biopsy-proven lupus nephritis was in most cases class IV(49.7% of all the biopsies). Oral ulcers were observed in 28% of patients. Neuropsychiatric manifestations, gastrointestinal involvement, and lymphadenopathy were observed in 31.5%, 8.3%, and 14.2% of patients, respectively. In all, 93% of patients were positive for antinuclear antibodies, whereas antidouble-stranded DNA was positive in 83% of patients. Coomb's positive hemolytic anemia appeared in 12.4% of the cases. Rheumatoid factor was detected in 9.7% of patients, and lupus erythematosus cell was seen in 32.5% of them. In all, 196 (47.8%) patients represented hypocomplementemia. Regarding hematological manifestations, 74.5% had microcytic hypochromic anemia, 64.6% had leukopenia, and 44.6% had thrombocytopenia; 18 (4.4%) patients died during the study period of which eight (2%) died because of cardiopulmonary involvement. Generally, there was more cutaneous, serositis, and neuropsychiatric involvement in our population than other Middle East countries. Serositis was associated with poorer prognosis, and the pattern of disease in these patients was much more sever than patients without serositis (P = 0.001). This is the first study of its kind in Iran. More multicenter studies should be undertaken in Iran to describe the pattern of SLE.

Protection of human and murine hepatocytes against Fas-induced death by transferrin and iron.

Recent studies in a murine model show that transferrin (Tf) interferes with Fas-mediated hepatocyte death and liver failure by decreasing pro-apoptotic and increasing anti-apoptotic signals. We show here in vitro in murine and human hepatocyte cell lines and in vivo in mice that Fas-induced apoptosis is modulated by exogenous Tf and iron. The results obtained with iron-free Tf (ApoTf), iron-saturated Tf (FeTf), and the iron chelator salicylaldehyde isonicotinoyl hydrazone (SIH) in its iron-free and iron-saturated (FeSIH) forms indicate that apoptosis-modulating effects of Tf are not mediated by iron alone. Both the Tf molecule and iron affect multiple aspects of cell death, and the route of iron delivery to the cell may be critical for the final outcome of cellular Fas signaling. Survival of hepatocytes 'stressed' by Fas signals can be manipulated by Tf and iron and may be a target for prophylactic and therapeutic interventions.