Tailored Concept for Accurate Neuroendoscopy: A Comparative Retrospective Single-Center Study on Image-Guided Neuroendoscopic Procedures.

OBJECTIVE: Precise planning and execution is key for neuroendoscopic interventions, which can be based on different available aiding technologies. The aim of this retrospective study is to report a case-based use of guided neuroendoscopy and to develop a stratification algorithm for the available technologies. METHODS: We reviewed consecutive neuroendoscopic cases performed at our center from 2016 to 2018. We distinguished between patients receiving a new burr hole (group A) and those with a preexisting burr hole (group B). Case-specific technical requirements for procedure planning and execution, complication rate, surgical outcome, and possible subsequent surgery were evaluated. From this experience, a stratification system was developed to tailor the available guiding technologies. RESULTS: A total of 309 neuroendoscopic interventions in 243 patients were included in the present study. The cases included hydrocephalic (81.6%) and nonhydrocephalic (18.4%) conditions. The interventions were supported by coordinate-based (group A, n = 49; group B, n = 67), guide-based (group A, n = 42; group B, n = 0), ultrasound-guided (group A, n = 50; group B, n = 7), or navigated augmented reality-guided (group A, n = 85; group B, n = 9) techniques. The overall complication rate was 4.5%. Stratified by the surgical indication, fontanel status, entry point localization, presence of a preexisting burr hole, ventricular size, and number of targets, an approach toward image-guided neuroendoscopy is suggested. CONCLUSIONS: Planning and technical guidance is essential in neuroendoscopic procedures. The stratified decision-making algorithm for different available technologies aims to achieve lower cost and time consumption, which was found to be safe and efficient. Further investigations are warranted to deliver solid data on procedure efficiency.

Navigated bedside implantation of external ventricular drains with mobile health guidance: technical note and case series.

PURPOSE: External ventricular drain (EVD) implantation is one of the fundamental procedures of emergency neurosurgery usually performed freehand at bedside or in the operating room using anatomical landmarks. However, this technique is frequently associated with malpositioning leading to complications or dysfunction. Here, we describe a novel navigated bedside EVD insertion technique, which is evaluated in a clinical case series with the aim of safety, accuracy, and efficiency in neurosurgical emergency settings. METHODS: From 2021 to 2022, a mobile health-assisted navigation instrument (Thomale Guide, Christoph Miethke, Potsdam, Germany) was used alongside a battery-powered single-use drill (Phasor Health, Houston, USA) for bedside EVD placement in representative neurosurgical pathologies in emergency situations requiring ventricular cerebrospinal fluid (CSF) relief and intracranial pressure (ICP) monitoring. RESULTS: In all 12 patients (8 female and 4 male), navigated bedside EVDs were placed around the foramen of Monro at the first ventriculostomy attempt. The most frequent indication was aneurysmal subarachnoid hemorrhage. Mean operating time was 25.8 ± 15.0 min. None of the EVDs had to be revised due to malpositioning or dysfunction. Two EVDs were converted into a ventriculoperitoneal shunt. Drainage volume was 41.3 ± 37.1 ml per day in mean. Mean length of stay of an EVD was 6.25 ± 2.8 days. Complications included one postoperative subdural hematoma and cerebrospinal fluid infection, respectively. CONCLUSION: Combining a mobile health-assisted navigation instrument with a battery-powered drill and an appropriate ventricular catheter may enable and enhance safety, accuracy, and efficiency in bedside EVD implantation in various pathologies of emergency neurosurgery without adding relevant efforts.

Biopsies of Caudal Brainstem Tumors in Pediatric Patients-A Single-Center Retrospective Case Series.

OBJECTIVE: The indication for performing biopsies in patients with diffuse lesions in the brain stem is controversial. The possible risks associated with the technically challenging interventions must be balanced against clarifying the diagnosis and the possible therapeutic options. We reviewed the feasibility, risk profile, and diagnostic yield of different biopsy techniques in a pediatric cohort. METHODS: We retrospectively included all patients aged <18 years who had undergone biopsy of the caudal brainstem region (pons, medulla oblongata) at our pediatric neurosurgical center from 2009 to 2022. RESULTS: We identified 27 children. Biopsies were performed using frameless stereotactic (Varioguide; n = 12), robotic-assisted (Autoguide; n = 4), endoscopic (n = 3), and open biopsy (n = 8) techniques. Intervention-related mortality was not observed. Three patients experienced a transient postoperative neurological deficit. No patient experienced intervention-related permanent morbidity. Biopsy yielded the histopathological diagnosis in all 27 cases. Molecular analysis was feasible for 97% of the cases. The most common diagnosis was H3K27M-mutated diffuse midline glioma (60%). Low-grade gliomas were identified in 14% of patients. Overall survival was 62.5% after 24 months of follow-up. CONCLUSIONS: Biopsies of the caudal brainstem in children were feasible and safe in the presented setup. The amount of tumor material acquired allowing for an integrated diagnosis and was obtained at reasonable risk. The selection of the surgical technique depends on the tumor location and growth pattern. We recommend the performance of brainstem tumor biopsies in children at specialized centers to better understand the biology and enable possible novel therapeutic options.

The Influence of Perioperative Antibiotic Prophylaxis on Wound Infection and on the Colonization of Wound Drains in Patients After Correction of Craniosynostosis.

Objective: Evidence for the duration of perioperative antibiotic prophylaxis (PAP) after the correction of craniosynostosis in children is scarce. We evaluated the necessary duration of PAP to ensure a minimal rate of postoperative wound infections. Methods: In this monocentric, retrospective, and prospective pilot study, two PAP protocols were compared. From August 2017 to May 2018, treatment group 1 (TG 1) was treated using the standard PAP protocol with at least three doses of antibiotics. Between May 2018 and March 2019, a shortened PAP with a single-shot administration was given to treatment group 2 (TG 2a and b). Endpoints of this study were wound infection rate, colonization rate of wound drains, and the course of treatment reflected by clinical and laboratory data. Results: A cohort of 187 children underwent craniosynostosis correction: 167 were treated according to protocols--95 patients with at least three doses (TG 1) and 72 patients with a single-shot of cefuroxime (TG 2a). Baseline characteristics were similar for both groups. We could not detect significant differences, neither for wound infection rates (TG 1: 1.1%, TG 2a: 0.0%, p = 0.38) nor for colonization rates of wound drains (TG 1: 4.8%, TG 2a: 10.5%, p = 0.27). Conclusions: Single-shot PAP had no adverse effects on the wound infection rate or the colonization rate of the wound drains compared with prolonged perioperative antibiotic prophylaxis. As a result, single-shot preoperative PAP is now applied to the majority craniosynostosis patients undergoing surgical correction in our unit.

Neuroendoscopic surgery in neonates - indication and results over a 10-year practice.

PURPOSE: Neuroendoscopic procedures for treatment of term and preterm newborn infants, such as endoscopic lavage for posthemorrhagic hydrocephalus, are gaining popularity despite sparse data. This single-institution report compiles all neuroendoscopic surgical procedures performed in neonates during a 10-year period. METHODS: Charts and electronic records were reviewed of all consecutive newborns who underwent a neuroendoscopic procedure before reaching a postmenstrual age of 44 weeks between 09/2010 and 09/2020. Available documentation was reviewed regarding the performed neuroendoscopic procedure, course of disease, complications, and all re-operations throughout the first year of life. RESULTS: During the 10-year study period, 116 infants (median gestational age at birth: 29 1/7 weeks) underwent a total of 153 neuroendoscopic procedures (median postmenstrual age at surgery: 35 0/7 weeks). The most common indication at the time of the neuroendoscopic procedures (n = 153) was intraventricular hemorrhage (IVH, n = 119), intraventricular infection (n = 15), congenital malformation (n = 8), isolated 4th ventricle (n = 7), multiloculated hydrocephalus (n = 3), and tumor (n = 1). Thirty-eight of 116 children (32.8%) underwent 43 operative revisions after 153 neuroendoscopic procedure (28.1%). Observed complications requiring surgical revision were secondary infection (n = 11), CSF fistula (n = 9), shunt dysfunction (n = 8), failure of ETV (n = 6), among others. 72 children (62%) of 116 children required permanent CSF diversion via a shunt. The respective shunt rates per diagnosis were 47 of 80 (58.8%) for previously untreated IVH, 11 of 13 (84.6%) for intraventricular infection. Shunt survival rate for the first year of life was 74% for the whole cohort. CONCLUSION: The experience with this large cohort of neonates demonstrates the feasibility of neuroendoscopic technique for the treatment of posthemorrhagic or postinfectious hydrocephalus. Rate and type of complications after neuroendoscopic procedures were within the expected range. Assessing the potential long-term benefits of neuroendoscopic techniques has to await results of ongoing studies.

Surgical management of intracranial arachnoid cysts in pediatric patients: radiological and clinical outcome.

OBJECTIVE: Congenital intracranial cysts account for a significant portion of intracranial lesions in the pediatric population. The efficiency of surgical treatment in a pediatric cohort with intracranial arachnoid cysts (ACs) at different locations regarding clinical symptoms and mass effect was evaluated. METHODS: A retrospective study of all children who underwent surgical treatment of an intracranial AC during an 11-year period (2007-2018) was performed. Demographics, clinical symptoms, and radiological cyst size pre- and postoperatively, as well as the reoperation rate and possible treatment complications, were analyzed. RESULTS: A total of 116 intracranial cysts at 8 different anatomical locations were surgically treated in 113 children (median age 5 years and 10 months) predominantly by endoscopic technique (84%). The complication rate was 3%, and the reoperation rate was 16%. Preoperative cyst enlargement was significantly more common in infants (p < 0.0001), as was the need for reoperation (p = 0.023). After a median radiological follow-up of 26 months, > 50% reduction of cyst volume was seen in 53 cysts (46%), and 47 cysts (40%) showed a 10%-50% reduction. Acute clinical symptoms improved: nausea and vomiting, accelerated head growth, and headaches improved at 100%, 92% and 89%, respectively. However, chronic symptoms responded less favorably after a median clinical follow-up of 26 months. CONCLUSIONS: The strategy of predominantly endoscopic treatment with navigation planning is efficient to alleviate clinical symptoms and to significantly reduce the mass effect of pediatric intracranial cysts at different anatomical locations. The subgroup of infants requires close pre- and postoperative monitoring.

First experience with augmented reality neuronavigation in endoscopic assisted midline skull base pathologies in children.

INTRODUCTION: Endoscopic skull base approaches are broadly used in modern neurosurgery. The support of neuronavigation can help to effectively target the lesion avoiding complications. In children, endoscopic-assisted skull base surgery in combination with navigation systems becomes even more important because of the morphological variability and rare diseases affecting the sellar and parasellar regions. This paper aims to analyze our first experience on augmented reality navigation in endoscopic skull base surgery in a pediatric case series. PATIENTS AND METHODS: A retrospective review identified seventeen endoscopic-assisted endonasal or transoral procedures performed in an interdisciplinary setting in a period between October 2011 and May 2020. In all the cases, the surgical target was a lesion in the sellar or parasellar region. Clinical conditions, MRI appearance, intraoperative conditions, postoperative MRI, possible complications, and outcomes were analyzed. RESULTS: The mean age of our patients was 14.5 ± 2.4 years. The diagnosis varied, but craniopharyngiomas (31.2%) were mostly represented. AR navigation was experienced to be very helpful for effectively targeting the lesion and defining the intraoperative extension of the pathology. In 65% of the oncologic cases, a radical removal was proven in postoperative MRI. The mean follow-up was 89 ± 79 months. There were no deaths in our series. No long-term complications were registered; two cerebrospinal fluid (CSF) fistulas and a secondary abscess required further surgery. CONCLUSION: The implementation of augmented reality to endoscopic-assisted neuronavigated procedures within the skull base was feasible and did provide relevant information directly in the endoscopic field of view and was experienced to be useful in the pediatric cases, where anatomical variability and rarity of the pathologies make surgery more challenging.

Reduced rates of infection after myelomeningocele closure associated with standard perioperative antibiotic treatment with ampicillin and gentamicin.

PURPOSE: Postnatal closure of a myelomeningocele (MMC) is a complex procedure with frequent complications following surgery. Bacterial colonization of the placode may cause infection and subsequent complications. The objectives of this study were to determine the preoperative bacterial colonization rates, to assess the antibiotic regimen, and to evaluate the overall postoperative infection rate. METHODS: All consecutive patients undergoing MMC closure in our hospital from January 2010 to January 2020 were evaluated. Epidemiological data, surgical data, complication characteristics, and microbiological results were documented. RESULTS: A total of 45 patients were evaluated; in 41 patients, a wound swab of the placode was performed directly before MMC closure (91%). All patients received a prophylactic antibiotic treatment for a mean of 5.6 ± 2.7 days around the performed MMC closure. In three patients with a wound swab (7.3%), a bacterial colonization could be detected-none of the patients developed a subsequent infection. Overall, 7 other patients developed an infection (15.6%), three local surgical site infections, and four shunt-related infections. After applying a standardized perioperative prophylactic antibiotic treatment with ampicillin and gentamicin, the infection rate was observed to be lower compared with that of a non-standardized treatment (6% vs. 45%; p = 0.019). CONCLUSIONS: In neonates who undergo MMC closure in the first 48 h after birth, the colonization rate of the placode was lower than previously reported. While the data presented cannot proof the benefit of a perioperative antibiotic prophylaxis, as compared with no prophylaxis, infection rates are low with a standardized antibiotic regime comprising ampicillin and gentamicin.

Secondary tethered cord syndrome in adult patients: retethering rates, long-term clinical outcome, and the effect of intraoperative neuromonitoring.

BACKGROUND: The strategy for surgical treatment of tethered cord syndrome in pediatric patients is well established but still bares challenges for adult patients. This retrospective study was performed to assess the surgical outcome of adult patients with a secondary tethered cord syndrome and to evaluate the benefit of intraoperative neuromonitoring. METHODS: Clinical charts of 32 consecutive adult patients who underwent in total 38 surgical untethering procedures at our facility between 2008 and 2018 were retrospectively analyzed. Epidemiological data, MRI scans, and postoperative results were evaluated. RESULTS: The retethering rate in our patient cohort was 16%. Main complaints were maximal pain (82%), bladder dysfunction (79%), paresthesia (68%), and weakness in the lower extremities (68%). Forty-eight months after surgery, patients' symptoms generally improved, with an average level of pain of 19.1% (95% CI, 5.7-32.5%), paresthesia 28.7% (95% CI, 12.6-44.8%), weakness in the lower extremities 27.7% (95% CI, 11.1-44.4%), and bladder dysfunction 60.2% (95% CI, 41.6-78.7%). The use of neuromonitoring appears to have a positive impact on patient weakness (OR = 0.07; 95% CI, 0.01-0.68) and paresthesia (OR = 0.03; 95% CI, 0.00-2.18). This benefit is less clear for the retethering rate (OR = 0.45; 95% CI, 0.06-3.26) or the overall clinical outcome (OR = 0.70; 95% CI, 0.14-3.45). The presence of a preoperative Chiari syndrome, syringomyelia, or scoliosis had no relevant influence on the retethering rate. CONCLUSIONS: Our data confirms that untethering surgery in adult patients is relatively safe and has a reasonable chance of clinical improvement of pain, paresthesia, and weakness in the lower extremities. The use of intraoperative monitoring has a positive influence on the improvement of preoperative paralysis.

Seizures following surgery for supratentorial extratemporal low-grade tumors in children: a multicenter retrospective study.

OBJECTIVE: Resection of brain tumors may lead to new-onset seizures but may also reduce seizure rates in patients presenting with seizures. Seizures are seen at presentation in about 24% of patients with brain tumors. For lesional epilepsy in general, early resection is associated with improved seizure control. However, the literature is limited regarding the occurrence of new-onset postoperative seizures, or rates of seizure control in those presenting with seizures, following resections of extratemporal low-grade gliomas (LGGs) in children. METHODS: Data were collected retrospectively from 4 large tertiary centers for children (< 18 years of age) who underwent resection of a supratentorial extratemporal (STET) LGG. The patients were divided into 4 groups based on preoperative seizure history: no seizures, up to 2 seizures, more than 2 seizures, and uncontrolled or refractory epilepsy. The authors analyzed the postoperative occurrence of seizures and the need for antiepileptic drugs (AEDs) over time for the various subgroups. RESULTS: The study included 98 children. Thirty patients had no preoperative seizures, 18 had up to 2, 16 had more than 2, and 34 had refractory or uncontrolled epilepsy. The risk for future seizures was higher if the patient had seizures within 1 month of surgery. The risk for new-onset seizures among patients with no seizures prior to surgery was low. The rate of seizures decreased over time for children with uncontrolled or refractory seizures. The need for AEDs was higher in the more active preoperative seizure groups; however, it decreased with time. CONCLUSIONS: The resection of STET LGGs in children is associated with a low rate of postoperative new-onset epilepsy. For children with preoperative seizures, even with uncontrolled epilepsy, most have a significant improvement in the seizure activity, and many may be weaned off their AEDs.

Retethering after transection of a tight filum terminale, postoperative MRI may help to identify patients at risk.

PURPOSE: Retethering after transection of a tight filum terminale (TFT) deemed to be a rare and usually only years after initial surgery occurring complication. Possible perioperative factors that might influence the retethering rate or help to allow a prognostic risk assessment are still poorly investigated. The aim of this study was to analyze our patient cohort who underwent a TFT transection by assessing clinical outcome, retethering rate, and pre- and postoperative MRI studies. METHODS: All consecutive patients undergoing transection of a TFT from January 2011 to December 2018 were evaluated. Inclusion criteria were defined as exclusive TFT intervention and a minimum follow up period of 1 year. Epidemiological data, treatment modalities, complication characteristics, and MRI studies were recorded and analyzed. RESULTS: A total of 58 patients met our inclusion criteria. The retethering rate in our patient cohort was 5.2% (3/58); one of the three patients developed two episodes of a retethering. Patients with an unchanged conus level, no improvement in the syringomyelia, and an unchanged thickness of the spinal cord postoperatively seem to have a significant higher risk to develop a retethering episode in the follow-up. CONCLUSION: Retethering after transection of the filum terminale did occur more often than expected. Certain existing factors on the routine postoperative MR images may help to identify patients with an increased likelihood to develop a retethering episode. These results may contribute to improve the follow-up for patients after transection of a TFT and may facilitate adequate treatment.

TROPHY registry study design: a prospective, international multicenter study for the surgical treatment of posthemorrhagic hydrocephalus in neonates.

INTRODUCTION: Among children with hydrocephalus, neonates with intraventricular hemorrhage (IVH) and posthemorrhagic hydrocephalus (PH) are considered a group with one of the highest complication rates of treatment. Despite continued progress in neonatal care, a standardized and reliable guideline for surgical management is missing for this challenging condition. Thus, further research is warranted to compare common methods of surgical treatment. The introduction of neuroendoscopic lavage has precipitated the establishment of an international registry aimed at elaborating key elements of a standardized surgical treatment. METHODS: The registry is designed as a multicenter, international, prospective data collection for neonates aged 41 weeks gestation, with an indication for surgical treatment for IVH with ventricular dilatation and progressive hydrocephalus. The following initial temporizing surgical interventions, each used as standard treatment at participating centers, will be compared: external ventricular drainage (EVD), ventricular access device (VAD), ventricular subgaleal shunt (VSGS), and neuroendoscopic lavage (NEL). Type of surgery, perioperative data including complications and mortality, subsequent shunt surgeries, ventricular size, and neurological outcome will be recorded at 6, 12, 36, and 60 months. RESULTS: An online, password-protected website will be used to collect the prospective data in a synchronized manner. As a prospective registry, data collection will be ongoing, with no prespecified endpoint. A prespecified analysis will take place after a total of 100 patients in the NEL group have been entered. Analyses will be performed for safety (6 months), shunt dependency (12, 24 months), and neurological outcome (60 months). CONCLUSION: The design and online platform of the TROPHY registry will enable the collection of prospective data on different surgical procedures for investigation of safety, efficacy, and neurodevelopmental outcome of neonates with IVH and hydrocephalus. The long-term goal is to provide valid data on NEL that is prospective, international, and multicenter. With the comparison of different surgical treatment modalities, we hope to develop better therapy guidelines for this complex neurosurgical condition.

Experience in shunt management on revision free survival in infants with myelomeningocele.

OBJECTIVE: Depending on the etiology of hydrocephalus in childhood, the shunt therapy still remains challenging due to frequent shunt complications leading to possible revisions such as shunt infection or shunt malfunction. In myelomeningocele (MMC) patients who often require shunt therapy, higher revisions rates were reported. In a single-center retrospective study, experiences on shunt regimen on hydrocephalus associated with MMC are presented. METHODS: Data of 160 infant hydrocephalus cases younger than 1 year of age at the time of implantation were retrospectively reviewed from the hospital database. These patients received an adjustable differential pressure valve with gravitational unit and antibiotic impregnated catheters as a primary or secondary implant during the time period of April 2007 to July 2015. The subgroup of infants cases with MMC (n = 44; age 50.6 ± 80.6 days) were compared to the remaining cohort of other hydrocephalus etiology (control group). The shunt and valve revision free survival rates were recorded until July 2017. RESULTS: During the mean follow-up of 48.7 ± 19.2 (7-114) months, the shunt revision free survival was 87% at 1 year and 49% at 60 months in the MMC cohort. The control group showed a shunt survival rate of 68% at 1 year and 39% at 60 months. Similarly, the valve revision free survival rate showed a significant higher rate of 92% at 1 year and 69% at 60 months in the MMC group compared to the control group (75% at 1 year and 51% at 60 months; p < 0.05). During the entire follow-up period, 37% of the MMC infants underwent a revision operation in contrast to the control group of 40%. CONCLUSION: The presented shunt strategy showed improved revision free survival rates in infants with a MMC-related hydrocephalus in comparison to other etiologies of hydrocephalus in infants, which might relate to infection prophylaxis and high drainage resistance integrated in the shunt system.

GAVCA Study: Randomized, Multicenter Trial to Evaluate the Quality of Ventricular Catheter Placement with a Mobile Health Assisted Guidance Technique.

BACKGROUND: Freehand ventricular catheter placement may represent limited accuracy for the surgeon's intent to achieve primary optimal catheter position. OBJECTIVE: To investigate the accuracy of a ventricular catheter guide assisted by a simple mobile health application (mhealth app) in a multicenter, randomized, controlled, simple blinded study (GAVCA study). METHODS: In total, 139 eligible patients were enrolled in 9 centers. Catheter placement was evaluated by 3 different components: number of ventricular cannulation attempts, a grading scale, and the anatomical position of the catheter tip. The primary endpoint was the rate of primary cannulation of grade I catheter position in the ipsilateral ventricle. The secondary endpoints were rate of intraventricular position of the catheter's perforations, early ventricular catheter failure, and complications. RESULTS: The primary endpoint was reached in 70% of the guided group vs 56.5% (freehand group; odds ratio 1.79, 95% confidence interval 0.89-3.61). The primary successful puncture rate was 100% vs 91.3% (P = .012). Catheter perforations were located completely inside the ventricle in 81.4% (guided group) and 65.2% (freehand group; odds ratio 2.34, 95% confidence interval 1.07-5.1). No differences occurred in early ventricular catheter failure, complication rate, duration of surgery, or hospital stay. CONCLUSION: The guided ventricular catheter application proved to be a safe and simple method. The primary endpoint revealed a nonsignificant improvement of optimal catheter placement among the groups. Long-term follow-up is necessary in order to evaluate differences in catheter survival among shunted patients.

Inhibition of term decidual NK cell cytotoxicity by soluble HLA-G1.

OBJECTIVES: Soluble (s)HLA-G1 is produced by trophoblast cells. Aim was to analyze the capacities and mechanisms of sHLA-G1 to regulate interleukin (IL)-2-induced cytotoxicity of natural killer (NK) cells from human deciduas. METHODS: Natural killer cells were isolated from decidual layers of term placentae, stimulated or not with IL-2 and supplemented with various concentrations of recombinant soluble HLA-G1 (sHLA-G1). For NK cell cytotoxicity assays, K562 cells were used as targets. Expression of signal transducer and activator of transcription 3 (STAT3) and perforin was analyzed by Western blotting. Apoptosis was examined by assessment of poly(ADP-ribose) polymerase cleavage. NK cells were analyzed by flow cytometry for IL-2receptor-alpha (IL-2R alpha; CD25) and transferrin receptor CD71 expression. RESULTS: Interleukin-2 increases CD71, STAT3, perforin expression and cytotoxic potential of NK cells. Expression of CD71, STAT3 and perforin decreased simultaneously with cytotoxicity and dose-dependently when sHLA-G1 (1.6 micro g/mL-1.6 ng/mL) was added to IL-2 stimulated cultures. sHLA-G1 did not induce apoptosis and CD25 expression was not affected. CONCLUSION: Interleukin-2R alpha expression is not controlled by sHLA-G1, but its signal transducer STAT3 as well as several downstream effects, such as perforin expression, proliferation and cytotoxicity. The control of STAT3 bioavailability through sHLA-G1 may be a key regulator of the mentioned effects.