Reply to Akça, B.; Bilotta, F. Time and Type of Administered Fluids during Cesarean Section Might Not Matter for Hemodynamic Outcomes, but There Are Significant Patient Safety Concerns Regarding Colloid Use in Parturients. Comment on "Theodoraki et al. Colloid Preload versus Crystalloid Co-Load in the Setting of Norepinephrine Infusion during Cesarean Section: Time and Type of Administered Fluids Do Not Matter. J. Clin. Med. 2023, 12, 1333".

We would like to take this opportunity to thank Drs Akça and Bilotta for their interest and their insightful comments [...].

Colloid Preload versus Crystalloid Co-Load in the Setting of Norepinephrine Infusion during Cesarean Section: Time and Type of Administered Fluids Do Not Matter.

Background and Goal of Study: Spinal anesthesia for cesarean section is frequently associated with a high incidence of hypotension, which may bring about untoward effects for both the mother and fetus. Recently, norepinephrine has emerged as a promising alternative in maintaining blood pressure in the obstetric setting. Fluid administration is another technique still widely used to prevent maternal hypotension. The optimal fluid strategy to prevent maternal hypotension has not been elucidated yet. It has been recently suggested that the main strategy in the prevention and management of hypotension should be the combination of vasoconstrictive medications and fluid administration. The aim of this randomized study was to compare the incidence of maternal hypotension in parturients receiving either colloid preload or crystalloid co-load in the setting of prophylactic norepinephrine infusion during elective cesarean section under combined spinal-epidural anesthesia. Materials and Methods: After ethics committee approval, 102 parturients with full-term singleton pregnancies were randomly allocated to either 6% hydroxyethyl starch 130/0.4 5 mL/kg before the onset of spinal anesthesia (colloid preload group) or Ringer's lactate solution 10 mL/kg concurrent with the subarachnoid injection (crystalloid co-load group). In both groups, norepinephrine 4 µg/min starting simultaneously with the administration of the subarachnoid solution was also administered. The primary outcome of the study was the incidence of maternal hypotension, defined as systolic arterial pressure (SAP) <80% of baseline. The incidence of severe hypotension (SAP < 80 mmHg), total dose of vasoconstrictive agents administered, as well as the acid-base status and Apgar score of the neonate and any incidence of maternal side effects were also recorded. Results: Data analysis was performed on 100 parturients: 51 in the colloid preload group and 49 in the crystalloid co-load group. No significant differences were demonstrated between the colloid preload group and the crystalloid co-load group in the incidence of hypotension (13.7% vs. 16.3%, p = 0.933) or the incidence of severe hypotension (0% vs. 4%, p = 0.238). The median (range) ephedrine dose was 0 (0-15) mg in the colloid preload group and 0 (0-10) mg in the crystalloid co-load group (p = 0.807). The incidence of bradycardia, reactive hypertension, requirement for modification of vasopressor infusion, time to the first occurrence of hypotension, and maternal hemodynamics did not differ between the two groups. There were no significant differences in other maternal side effects or neonatal outcomes between groups. Conclusions: The incidence of hypotension with a norepinephrine preventive infusion is low and comparable with both colloid preload and crystalloid co-load. Both fluid-loading techniques are appropriate in women undergoing cesarean delivery. It appears that the optimal regimen for prevention of maternal hypotension is a combined strategy of a prophylactic vasopressor such as norepinephrine and fluids.

Unusual Case of a Parasitic Extra-Uterine Leiomyoma Presenting With Lower Abdominal Pain.

Parasitic fibroids are a rare type of extrauterine benign tumors that may be spontaneous or iatrogenic in origin and often difficult to diagnose due to their various presentations. We report an unusual case of a parasitic leiomyoma in a 33-year-old nulliparous woman with remote pelvic history who presented to our institution with sudden-onset lower abdominal pain. We performed an exploratory laparotomy, which revealed a 6.3x4.6 cm mass in the space of the adnexa of the right parametrium. Histopathological examination revealed features compatible with a leiomyoma. It is clear that physicians need to assess clinical findings and imaging techniques in order to establish a correct diagnosis of parasitic myomas, even when a history of myomectomy or a laparoscopic morcellation is absent.

Researching the Phenomenon of Poor Ovarian Responders and Management Strategies in IVF: A Narrative Review.

This narrative review aims to summarize all the latest studies published between 2015-2021 concerning the management protocols adopted for poor ovarian response (POR) cases. Patients defined as "poor responders" show minimal response to controlled ovarian hyperstimulation, although there is no standard definition for POR. Although infertility specialists are endeavoring to improve cycle outcomes in poor responders by adopting multiple management strategies, still the estimated risk of cycle cancellation is about 20%. All the studies performed during this study period were evaluated and their results were recorded. The latest published protocols to improve oocyte retrieval in poor responders include: anti-Mϋllerian hormone, clomiphene citrate, co-enzyme Q10, corifollitropin, dehydroepiandrosterone, double stimulation, Follicle Stimulation Hormone, Growth Hormone, Gonadotropin-releasing hormone agonists, letrozole, human chorionic gonadotropin, Luteinizing Hormone, progesterone and testosterone. CONCLUSION: Although many strategies have been suggested to manage POR, none has been proven superior to the others. Further large-scale randomized studies are needed to validate experimental techniques leading towards successful individualized treatment regimens.

Peripartum Ηysterectomy: A Four-Year Obstetric and Anesthetic Experience in a Tertiary Referral Hospital in Greece.

Background Although peripartum hysterectomy (PH) is a life-saving procedure in cases of abnormal placentation and postpartum hemorrhage, it can be associated with major obstetric and anesthetic complications. This retrospective study aimed to evaluate the incidence, etiology, perioperative anesthetic and obstetric management, complications, and fetal outcomes in women undergoing PH in a single tertiary referral hospital in Greece. Methodology This was a retrospective analysis of medical records of women who underwent emergency or elective PH in our hospital between January 2015 and December 2018. Results During the study period, 69 women who underwent a PH were identified. The incidence rate of elective and emergency PH was 4 and 1.2 per 1,000 deliveries, respectively. The main indication for PH was abnormal placentation (81.2%), followed by uterine atony (13%). Conversion to general anesthesia (GA) was performed in 21 (30.4%) cases. Conclusions This study showed a high prevalence of PH in our hospital compared to high-income countries. A neuraxial-only technique may be a safe alternative in individual cases of abnormal placentation. Conversion to GA can be reserved for complex surgical cases when massive hemorrhage is anticipated and, if possible, after the neonate has been delivered.

Prevalence of postpartum depression and antenatal anxiety symptoms during COVID-19 pandemic: An observational prospective cohort study in Greece.

INTRODUCTION: A significant proportion of pregnant women and women in the early postpartum period suffer from mental health problems. The COVID-19 pandemic represents a unique stressor during this period and many studies across the world have shown elevated rates of postpartum depression (PPD). METHODS: In this multicenter two-phase observational prospective cohort study, we aim to assess the prevalence of anxiety prior to labor (Generalized Anxiety Disorder-7), as well as PPD at 6-8 weeks postpartum using the Edinburgh Postnatal Depression Scale (EPDS). RESULTS: Of the 330 women analyzed, 13.2% reported symptoms of depression using EPDS cut-off score ≥13. High antenatal levels of anxiety (24.8% scored ≥10 in GAD-7) were documented. A significant proportion of postpartum women reported a decrease in willingness to attend antenatal education courses (36%) and fewer antenatal visits to their obstetrician (34%) due to pandemic. Higher antenatal anxiety increased the odds of being depressed at 6-8 weeks postpartum (EPDS ≥13). CONCLUSIONS: Compared to reported prevalence of PPD from previous studies before the COVID-19 era in Greece, we did not find elevated rates during the first wave of the pandemic. High anxiety levels were observed indicating that there is a need for close monitoring in pregnancy during the pandemic and anxiety screening to identify women who need support in the pandemic era. A well-planned maternity program should be employed by all the associated care providers to maintain the proper antenatal care adjusted to the pandemic strains as well as a follow-up after labor.

Paracentesis of an Ovarian Cyst During Second-Trimester Pregnancy.

A common issue is that modern obstetricians are required to manage ovarian cysts during pregnancy. Most lesions are benign and will spontaneously resolve, with a few exceptions. Management practices include conservative observation or surgery. Asymptomatic women with an ovarian cyst larger than 5 cm should undergo serial ultrasounds up to 16 weeks of pregnancy and, if the mass does not regress, further management with imaging or surgery is to be considered. This article presents a case of an ovarian cyst sized 21 cm in a second-trimester pregnancy and its management. Paracentesis was performed due to persisting symptoms. The procedure was performed with no complications for the mother and no adverse effects for the fetus. The patient was discharged in good health.

Peripartum Management of Gitelman Syndrome for Vaginal Delivery: A Case Report and Review of Literature.

We describe the anesthetic management of a spontaneous vaginal delivery at 38 weeks' gestation in a 36-year-old patient with Gitelman syndrome (GS). GS is a rare autosomal recessive renal tubulopathy characterized by hypomagnesemia, hypocalciuria, and secondary aldosteronism, which results in hypokalemia and metabolic alkalosis. To minimize any increase in catecholamine levels and consequent risk of ventricular arrhythmias, a labor epidural analgesia was administered using ropivacaine and fentanyl, along with intravenous magnesium and potassium supplementation. Ropivacaine was substituted for routine bupivacaine to decrease the risk of drug-induced cardiotoxicity. In the event of a cesarean section, the anesthetic plan was to continue with top-up epidural anesthesia and in case of failure, to convert to general anesthesia using propofol and rocuronium for induction. Delivery outcome was successful and uneventful.

Ketamine-induced neurotoxicity in neurodevelopment: A synopsis of main pathways based on recent in vivo experimental findings.

Ketamine, a phencyclidine derivative and N-methyl-D-aspartate (NMDA) receptor antagonist, is widely used as an anesthetic, analgesic, and sedative agent in daily pediatric practice. Experimental studies have suggested that early prenatal or postnatal exposure to ketamine can induce neuroapoptosis, and establish neurobehavioral deficits that are evident in adulthood. However, most of the currently available clinical evidence is derived from retrospective and observational clinical studies. We, herein, attempt a brief review of the cellular and molecular mechanisms suggested to mediate ketamine-induced developmental neurotoxicity, utilizing a selected number of recent in vivo experimental evidence.

Intraoperative Myomectomy during Caesarean Section.

OBJECTIVE: The aim of this article is to support intracaesarian myomectomy as an alternative method of treatment. CASE REPORT: This article presents a case of myomectomy during a caesarean section at 38+1 weeks' gestation, with a subserosal myoma on the left wall of the uterus. CONCLUSION: The postoperative period was free of complications, lending credit to the possibility that intracaesarean myomectomy can have a favourable outcome.

Cancer pain who cares? International and national patterns of evidence-based global guidelines recommendations for physicians on the Web (2011 vs. 2018).

PURPOSE: Although pain is a common event during treatment of cancer, its assessment and management remains suboptimal in everyday clinical practice at global level. METHODS: Considering both the important role of internet in daily life and that clinical guidelines are important for translating evidence in clinical practice, we performed a prospective study to scrutinize the magnitude of updated evidence-based cancer-pain guideline recommendation for physicians on the web. Changes over-time at a global level were scrutinized at two time points: 2011 for baseline and 2018 at first follow-up. Both anesthesiology and oncology societies were analyzed. RESULTS: In 2011 we scrutinized 181,00 WebPages and 370 eligible societies were identified; 364 of these were eligible for analyses both in 2011 and 2018. The magnitude of cancer pain updated and evidence-based guideline recommendations on the web for health care providers was extremely low at global level and at any time point considered: 1.1% (4/364) in 2011 and 4.7% (17/364) in 2018. Continental and intercontinental patterns, National's highest developmental index, oncology tradition and economic-geographic areas were not found to influence cancer pain web-guideline provision. In 2018, pain & supportive care societies provided the highest rate of updated evidence-based cancer-pain guidelines for clinicians. Only 3/25 medical oncology societies and 1/34 radiation oncology societies, provided own or e-link (to other societies') evidence-based guidelines in their websites. CONCLUSIONS: Major medical oncology and radiation oncology societies - at global level - fail to produce updated cancer pain recommendations for their physicians, with most of these providing no or inconsistent or outdated guidelines.

Facing internet fake-medicine and web para-pharmacy in the total absence of official recommendations from medical societies.

PURPOSE: Internet fake information, parapharmacy and counterfeit drugs are a market of hundreds of billion dollars. Misleading internet data decrease patients' compliance to medical care, promote use of questionable and detrimental practices, and jeopardize patient outcome. This is particularly harmful among cancer patients, especially when pain and nutritional aspects are considered. Provision of Web recommendations for the general audience (patients, relatives, general population) from official medical-providers might be useful to outweigh the detrimental internet information produced by non-medical providers. METHODS: 370 oncology and anesthesiology related societies were analyzed. Our objective was to evaluate the magnitude of web-recommendation for cancer cachexia and cancer pain for the general audience provided by official medical organizations' web sites at global level. RESULTS: Magnitude of web-recommendations at global level was surprisingly scant both for coverage and consistency. Seven official medical societies provided updated web-recommendation for cancer cachexia to their patients/family members, and 15 for cancer pain. Scantiness was unrelated by continent, developmental index, oncology tradition, economic-geographic area and society type scrutinized. CONCLUSIONS: Patients need expert advice when exposed to fake internet information largely dominated by paramedical market profits. In this era of "new media" the patients' net-education represents a new major educational challenge for medical societies.

Management of a Pregnant Patient With Central Poststroke Pain Syndrome Ultimately Having a Cesarean Delivery: A Case Report.

Cerebrovascular events, along with the early presentation of central pain, during pregnancy, are uncommon. We report a case of a parturient with intense central poststroke pain after an ischemic cerebrovascular incident at 15 weeks of gestation, attributed to cerebral venous thrombosis. After a multidisciplinary team consultation, she was scheduled for cesarean delivery at 35 weeks of gestation, under combined spinal-epidural anesthesia. Due to severe left-sided neurological deficits and ipsilateral intense neuropathic pain, the neuraxial technique was successfully performed using the paramedian approach.

Exposure to ethanol during neurodevelopment modifies crucial offspring rat brain enzyme activities in a region-specific manner.

The experimental simulation of conditions falling within "the fetal alcohol spectrum disorder" (FASD) requires the maternal exposure to ethanol (EtOH) during crucial neurodevelopmental periods; EtOH has been linked to a number of neurotoxic effects on the fetus, which are dependent upon the extent and the magnitude of the maternal exposure to EtOH and for which very little is known with regard to the exact mechanism(s) involved. The current study has examined the effects of moderate maternal exposure to EtOH (10 % v/v in the drinking water) throughout gestation, or gestation and lactation, on crucial 21-day-old offspring Wistar rat brain parameters, such as the activities of acetylcholinesterase (AChE) and two adenosine triphosphatases (Na(+),K(+)-ATPase and Mg(2+)-ATPase), in major offspring CNS regions (frontal cortex, hippocampus, hypothalamus, cerebellum and pons). The implemented experimental setting has provided a comparative view of the neurotoxic effects of maternal exposure to EtOH between gestation alone and a wider exposure timeframe that better covers the human third trimester-matching CNS neurodevelopment period (gestation and lactation), and has revealed a CNS region-specific susceptibility of the examined crucial neurochemical parameters to the EtOH exposure schemes attempted. Amongst these parameters, of particular importance is the recorded extensive stimulation of Na(+),K(+)-ATPase in the frontal cortex of the EtOH-exposed offspring that seems to be a result of the deleterious effect of EtOH during gestation. Although this stimulation could be inversely related to the observed inhibition of AChE in the same CNS region, its dependency upon the EtOH-induced modulation of other systems of neurotransmission cannot be excluded and must be further clarified in future experimental attempts aiming to simulate and to shed more light on the milder forms of the FASD-related pathophysiology.

Can acetylcholinesterase activity be considered as a reliable biomarker for the assessment of cadmium-induced neurotoxicity?

Gonçalves et al. (2012) recently reported the findings of a long-awaited study on the effects of long-term dietary-induced exposure to cadmium (Cd) on the acetylcholinesterase (AChE) activity of adult rodents' brain regions. Their study can be regarded as a significant contribution to the field, as there is paucity of information on the AChE activity in brain regions following exposure to Cd. However, the Cd-induced modulation of AChE activity is an issue surrounded by controversy. We, herein, discuss and summarize the relative in vivo and in vitro experimental data, and set out to answer the straightforward question: can AChE activity be considered as a reliable biomarker for the assessment of Cd-induced neurotoxicity? At this time, we can not answer in the affirmative because of the variation in techniques used and conclusions reached. We make a plea that authors aiming to explore this potential use of brain AChE activity in the future: (a) are aware of the biases that their experimental approach might exert upon this neurochemical parameter, (b) avoid the use of anaesthesia as a mode of sacrifice and clarify its timing, (c) decide upon the use of previously-studied in vivo experimental schemes (so that they can provide comparable results), and finally, (d) identify pharmacological, biochemical and molecular approaches that are appropriate to clarify the implicated mechanism(s) through which Cd modifies AChE activity.

Cancer cachexia: global awareness and guideline implementation on the web.

BACKGROUND: Cancer cachexia is a common associate of cancer and has a negative impact on patients' survival. Nonetheless, cancer cachexia assessment and management are frequently less than satisfactory in daily practice. AIM: To scrutinise global cancer cachexia awareness and relative web guideline implementation among oncology societies. METHODS: Systematical identification of scientific and policymaker oncology societies and their guideline implementation on cancer cachexia. Assessment of the general level of awareness on cancer cachexia and evaluation of intercontinental and national variations on guideline implementation. RESULTS: 144,000 web pages were scrutinised, and 275 oncology societies identified covering a large array of oncology setting (educational/clinical/research/policymaker); 71 were international (African, American, Asian, European, Oceania and Intercontinental), 110 belonged to the top 10 countries with the highest development index and 94 pertained to 10 countries with a long lasting tradition in medical oncology (not included in the top 10 high developed countries). Overall, only 10/275 web sites provided guidelines; six of them (2.2%) provided guidelines for physicians and four (0.7%) for patients. Half of the guidelines (4/10) were outdated. All guidelines for physicians reported references, while only one of the recommendations for patients reported references to support its sentences. CONCLUSIONS: Cancer cachexia global awareness appears extremely low; guideline implementation on the web was inconsistent for any category analysed (nation vs continent vs international vs society type vs physician vs patient oriented) and for updating.

Serotoninergic impairment and aggressive behavior in Alzheimer's disease.

The overall goal of all therapeutic interventions in Alzheimer's disease (AD) is to: (a) optimize the impaired functions and (b) restore an affordable quality of life for both the patient and his surroundings. AD has been characterized by a significant serotoninergic impairment. It is well known that impaired serotoninergic function is related to aggressive behavior. We, herein, review the past and recent evidence that seems to link the serotoninergic system with aggressive manifestations in AD patients. Managing the aggressive behavior of these patients might be of significant medical, social and economical importance. However, there is still a long way to go until we verify the exact pathophysiological mechanism(s) involved in the induction of aggression in AD patients. The current data underlines a complex relationship between the observed serotoninergic impairment in AD patients and the (a) cholinergic system, (b) the endocrine (hormonal) state, (c) the nutritional habits, (d) the genetic background and (e) the caregiving environment.