Rathke's cyst with xanthogranulomatous change or chronic cystic craniopharingioma? A rare case.

A 9-year-old girl presented to our neurosurgery clinic complaining of visual disturbances for a week. Magnetic resonance imaging showed an extensive sellar lesion with suprasellar involvement and compression of the optic chiasm. Based on these findings, a cystic craniopharyngioma, a pituitary macroadenoma and - less likely - a Rathke's cleft cyst were considered as differential diagnoses. In view of the progressive loss of vision, the parents agreed to resection of the lesion through an endoscopic endonasal transtubercular approach, with the aim of a gross total resection. Microscopic examination revealed that the lesion was cystic, surrounded by an epithelium that was partly composed of columnar ciliated cells with interspersed mucous cells and partly had a flattened appearance. The observed findings were complex to interpret: if, on the one hand, the clinical-surgical and neuroradiologic data suggested a craniopharyngioma, this hypothesis was not supported by the microscopic data, because the presence of columnar ciliated epithelium associated with mucous cells was a microscopic feature inconsistent with a craniopharyngioma and was instead consistent with a Rathke's cleft cyst, a histologic diagnosis that was made. The incidence of Rathke's cleft cyst, which mimics clinical and neuroradiologic aspects of craniopharyngiomas, is extremely unusual, as only 2 cases have been described in the literature.

Poly-D,L-lactic acid polymer and cochlear implantation.

This case report describes a peculiar and innovative fixing procedure with a Poly-D,L-lactic acid (PDLLA) polymer in the unusual case of magnet dislodgment and rupture of the cochlear implant (CI) silicone sheath holding the magnet.

Post-Operative Patients' Satisfaction and Quality of Life Assessment in Adult Patients with Obstructive Sleep Apnea Syndrome (OSAS).

BACKGROUND: The treatment for severe OSAS includes maxillomandibular advancement surgical option in selected cases. The aim of this study was to evaluate the post-operative impact of bimaxillary surgery on satisfaction and consequently the quality of life of these patients. METHODS: This study included 18 patients with severe OSAS who received maxillomandibular advancement surgery. Patients were divided into Group A (operated by CAD/CAM) and Group B (conventional surgery). The impact of bimaxillary surgery on satisfaction and quality of life of these patients was evaluated by utilizing post-operative life quality and Rustemeyer's patient-satisfaction-based survey. RESULTS: A total of 18 adult OSAS patients (Group A: 11 patients, Group B: 7 patients) with a mean age of 44.39 years (SD ± 9.43) were included. Mean follow-up period was 32.64 months (SD ± 21.91). No intra-operative complications were seen in any patients. Post-operative complication was seen in one patient and the mandible did not integrate. According to the results, overall post-operative satisfaction score was 79.72% (SD ± 9.96). There was no significant difference among those in Group A and Group B. CONCLUSIONS: Maxillomandibular advancement surgery seems to be beneficial in terms of patients' satisfaction in severe adult OSAS patients and can be considered as a valuable option in selected cases.

Pediatric pituitary adenoma with mixed FSH and TSH immunostaining and FSH hypersecretion in a 6 year-old girl with precocious puberty: case report and multidisciplinary management.

OBJECTIVE: We describe a rare case of functioning gonadotropins-producing pediatric adenoma immunostaining positively for FSH and focally for TSH causing central precocious puberty associated to central hypothyroidism in a 6 year-old girl. MATERIALS AND METHODS: Clinical evaluation revealed precocious puberty, as confirmed by hormonal determination with elevated FSH and estradiol, while central hypothyroidism was biochemically diagnosed by a low fT4 and normal TSH. Head MRI showed the presence of a hyperintense pituitary lesion. The patient successfully underwent transsphenoidal endoscopic resection of the pituitary macroadenoma. RESULTS: Pathologic evaluation of the tissue resected at surgery confirmed the diagnosis of pituitary adenoma with positive immunohistochemistry for FSH and focally for TSH in a mixed pattern. Ten months after surgery, there were no neurological signs and symptoms. Postoperative head MRI showed no abnormalities and no evidence of tumor regrowth. CONCLUSIONS: Early and accurate diagnosis, multidisciplinary approach and close follow up are crucial factors for the favorable outcome.

Evaluation of acromegaly treatment direct costs with respect to biochemical control and follow-up length.

PURPOSE: Acromegaly is a severe chronic endocrine disease. Achieving biochemical control often needs a multimodal treatment approach, including prolonged medical treatment. Aim of the study is to evaluate the burden of treatment direct costs with respect to the different therapeutic strategies, disease control, and follow-up length. METHODS: Single center retrospective study on 73 acromegaly patients. Costs of acromegaly treatments were computed based on a detailed revision of patients' clinical charts. RESULTS: Median total treatment cost/patient was €47,343 during the entire follow-up (8 years), while median treatment cost/patient/year was €6811. The majority of patients received medical therapy (71/73, 97.3%). Median cost for first-line medical treatment (first-generation somatostatin receptor ligands) was lower compared to second-line treatments (pegvisomant monotherapy or combination therapies), considering both total (€22,824 vs €76,140; p < 0.001), and yearly cost/patient (€4927 vs €9161; p < 0.001). Sixty patients (82.2%) reached biochemical control at last follow-up (IGF-1 ≤ 1 xULN). The percentage of patients treated with first- or second-line medical therapies was comparable between controlled and uncontrolled patients (p = 1.000), and the yearly cost/patient did not significantly differ between the two groups (€6936 vs €6680; p = 0.829). Follow-up duration was significantly longer in controlled patients compared to the uncontrolled ones (8.7 vs 3.5 years; p = 0.019). CONCLUSIONS: Direct costs for the management of acromegaly have a significant burden on the healthcare systems. However, more than 80% of our patients reached biochemical control using multimodal approaches. Treatment modalities and yearly costs did not significantly differ between controlled and uncontrolled patients, while follow-up length represented a major determinant of biochemical outcome.

A metabolic inhibitor arms macrophages to kill intracellular fungal pathogens by manipulating zinc homeostasis.

Macrophages deploy numerous strategies to combat invasion by microbes. One tactic is to restrict acquisition of diverse nutrients, including trace metals, a process termed nutritional immunity. Intracellular pathogens adapt to a resource-poor environment by marshaling mechanisms to harvest nutrients. Carbon acquisition is crucial for pathogen survival; compounds that reduce availability are a potential strategy to control intracellular replication. Treatment of macrophages with the glucose analog 2-deoxy-D-glucose (2-DG) armed phagocytes to eliminate the intracellular fungal pathogen Histoplasma capsulatum in vitro and in vivo. Killing did not rely on altering access to carbon-containing molecules or changes in ATP, ER stress, or autophagy. Unexpectedly, 2-DG undermined import of exogenous zinc into macrophages, decreasing the quantity of cytosolic and phagosomal zinc. The fungus perished as a result of zinc starvation. This change in metal ingress was not ascribed to a defect in a single importer; rather, there was a collective impairment in transporter activity. This effect promoted the antifungal machinery of macrophages and expanded the complexity of 2-DG activities far beyond manipulating glycolysis. Mechanistic metabolic studies employing 2-DG will have to consider its effect on zinc transport. Our preclinical data support consideration of this agent as a possible adjunctive therapy for histoplasmosis.

Role of Anterior Nasal Packing in Endoscopic Skull Base Surgery: Italian Survey.

BACKGROUND: Nowadays, the endoscopic endonasal approach to sellar and parasellar region tumors is a common technique in neurosurgery, and surgical nuances, complications, and management strategies are shared in a multidisciplinary setting between neurosurgeons and ear, nose, and throat surgeons. Due to the heterogeneity of its variations, the role of the anterior nasal packing in endoscopic endonasal approach to the skull base surgery (EESBS) has not yet been unanimously accepted and no consensus or guidelines on its use exist. MATERIALS AND METHODS: A survey containing 10 questions about indications, management advantages, and pitfalls of the use of anterior nasal packing in EESBS was created by using an online open-source tool (SurveyMonkey). The questionnaire was sent to 39 Italian neurosurgical departments, which routinely adopt the endoscopic endonasal approach. RESULTS: Almost half of 39 selected centers (19; 48.7%) answered our survey. The main results can be summarized as 1) anterior nasal packing after EESBS is considered useful by 84% of participants, 2) prevention of epistaxis is the principal indication for anterior nasal packing, 3) the type of approach and skull base reconstruction influence the use of anterior nasal packing, and 4) nasal discomfort is considered the principal negative aspect of nasal packing. CONCLUSIONS: Our study identified that anterior nasal packing is commonly adopted in certain conditions, namely when extensive nasal dissection is performed. Furthermore, the choice to adopt or not the anterior nasal packing should be tailored taking in account specific conditions, such as acromegaly and Cushing disease. It represents an important factor in reducing postoperative sinonasal complications of EESB.

Clinical and Radiological Predictors of Biochemical Response to First-Line Treatment With Somatostatin Receptor Ligands in Acromegaly: A Real-Life Perspective.

Background: First-generation somatostatin receptor ligands (fg-SRLs) represent the first-line medical treatment for acromegaly, recommended in patients with persistent disease after neurosurgery, or when surgical approach is not feasible. Despite the lack of strong recommendations from guidelines and consensus statements, data from national Registries report an increasing use of medical therapy as first-line treatment in acromegaly. Objective: We retrospectively evaluated the potential role of a large number of clinical and radiological parameters in predicting the biochemical response to 6-month treatment with fg-SRLs, in a cohort of naïve acromegaly patients referred to a single tertiary center for pituitary diseases. Methods: Univariable and multivariable logistic regression and linear regression analyses were performed. Biochemical response was defined based on IGF-1 levels, represented as both categorical (tight control, control, >50% reduction) and continuous (linear % reduction) variables. Results: Fifty-one patients (33 females, median age 57 years) were included in the study. At univariable logistic regression analysis, we found that younger age (≤ 40 years; OR 0.04, p=0.045) and higher BMI (OR 0.866, p=0.034) were associated with a lower chance of achieving >50% IGF-1 reduction. On the contrary, higher IGF-1 xULN values at diagnosis (OR 2.304, p=0.007) and a T2-hypointense tumor (OR 18, p=0.017) were associated with a significantly higher likelihood of achieving >50% IGF-1 reduction after SRL therapy. Of note, dichotomized age, IGF1 xULN at diagnosis, and T2-hypointense signal of the tumor were retained as significant predictors by our multivariable logistic regression model. Furthermore, investigating the presence of predictors to the linear % IGF-1 reduction, we found a negative association with younger age (≤ 40 years; ß -0.533, p<0.0001), while a positive association was observed with both IGF-1 xULN levels at diagnosis (ß 0.330, p=0.018) and the presence of a T2-hypointense pituitary tumor (ß 0.466, p=0.019). All these variables were still significant predictors at multivariable analysis. Conclusions: Dichotomized age, IGF-1 levels at diagnosis, and tumor T2-weighted signal are reliable predictors of both >50% IGF-1 reduction and linear % IGF-1 reduction after 6 month fg-SRL treatment in naïve acromegaly patients. These parameters should be considered in the light of an individualized treatment for acromegaly patients.

Octreotide and Pasireotide Combination Treatment in Somatotroph Tumor Cells: Predominant Role of SST2 in Mediating Ligand Effects.

First-generation somatostatin receptor ligands (fg-SRLs), such as octreotide (OCT), represent the first-line medical therapy in acromegaly. Fg-SRLs show a preferential binding affinity for somatostatin receptor subtype-2 (SST2), while the second-generation ligand, pasireotide (PAS), has high affinity for multiple SSTs (SST5 > SST2 > SST3 > SST1). Whether PAS acts via SST2 in somatotroph tumors, or through other SSTs (e.g., SST5), is a matter of debate. In this light, the combined treatment OCT+PAS could result in additive/synergistic effects. We evaluated the efficacy of OCT and PAS (alone and in combination) on growth hormone (GH) secretion in primary cultures from human somatotroph tumors, as well as on cell proliferation, intracellular signaling and receptor trafficking in the rat GH4C1 cell line. The results confirmed the superimposable efficacy of OCT and PAS in reducing GH secretion (primary cultures), cell proliferation, cAMP accumulation and intracellular [Ca2+] increase (GH4C1 cells), without any additive effect observed for OCT+PAS. In GH4C1 cells, co-incubation with a SST2-selective antagonist reversed the inhibitory effect of OCT and PAS on cell proliferation and cAMP accumulation, while both compounds resulted in a robust internalization of SST2 (but not SST5). In conclusion, OCT and PAS seem to act mainly through SST2 in somatotroph tumor cells in vitro, without inducing any additive/synergistic effect when tested in combination.

In Vitro and In Vivo Effect of Peptides Derived from 14-3-3 Paracoccidioides spp. Protein.

BACKGROUND: Paracoccidioidomycosis (PCM) is a chronic disease that causes sequelae and requires prolonged treatment; therefore, new therapeutic approaches are necessary. In view of this, three peptides from Paracoccidioides brasiliensis 14-3-3 protein were selected based on its immunogenicity and therapeutic potential. METHODS: The in vitro antifungal activity and cytotoxicity of the 14-3-3 peptides were evaluated. The influence of the peptides in immunological and survival aspects was evaluated in vivo, using Galleria mellonella and the expression of antimicrobial peptide genes in Caenorhabditis elegans. RESULTS: None of the peptides were toxic to HaCaT (skin keratinocyte), MRC-5 (lung fibroblast), and A549 (pneumocyte) cell lines, and only P1 exhibited antifungal activity against Paracoccidioides spp. The peptides could induce an immune response in G. mellonella. Moreover, the peptides caused a delay in the death of Paracoccidioides spp. infected larvae. Regarding C. elegans, the three peptides were able to increase the expression of the antimicrobial peptides. These peptides had essential effects on different aspects of Paracoccidioides spp. infection showing potential for a therapeutic vaccine. Future studies using mammalian methods are necessary to validate our findings.

Ipsilateral Nasoseptal Flap Pedicle for Transpterygoid Approach: Technical Note.

INTRODUCTION: Transpterygoid approach is an expanded endonasal approach (EEA) that allows surgical access to the medial infratemporal fossa, to the skull base area of petrous bone and to the Meckel's cave. During this approach, a sacrifice of sphenopalatine artery is often required, leading to the need of contralateral Hadad-Bassagasteguy flap (HBF) or alternative reconstructive techniques. MATERIALS AND METHODS: We report a case of spontaneous CSF leak due to a meningo-encephalocele in the left lateral recess of sphenoid sinus, in which an ispilateral nasoseptal flap was harvest and sphenopalatine artery was preserved. RESULTS: We described the surgical technique adopted to preserve the ipsilateral nasoseptal vascular pedicle during transpterygoid approach and we performed a review of the pertinent literature. CONCLUSION: Wide exposure of the pterygoid base through transpterygoid approach could be obtained preserving the sphenopalatine artery, allowing skull base reconstruction with ipsilateral nasoseptal flap.

The role of external ventricular drainage for the management of posterior cranial fossa tumours: a systematic review.

Posterior cranial fossa tumours frequently develop hydrocephalus as first presentation in up to 80% of paediatric patients and 21.4% of adults, although it resolves after tumour removal in 70-90% and 96%, respectively. New onset hydrocephalus is reported in about 2.1% of adult and 10-40% of paediatric patients after posterior fossa surgery. There is no consensus concerning prophylactic external ventricular drainage (EVD) placement that is frequently used before posterior fossa lesion removal, as well in those cases without clear evidence of hydrocephalus. The aim of the study was to define the most correct management for patients who undergo posterior fossa tumour surgery, thus identifying cohorts of patients who are at risk of persistent hydrocephalus prior to surgery. A systematic review of literature has been performed, following PRISMA guidelines. Most of the studies reported CSF shunt only in the presence of hydrocephalus, whereas only a few authors suggested its prophylactic use in the absence of signs of ventricular dilatation. Predictive factors for postoperative hydrocephalus has been identified, including young age (< 3 years), severe symptomatic hydrocephalus at presentation, EVD placement before surgery, FOHR index > 0.46 and Evans index > 0.4, pseudomeningocele, CSF leak and infection. The use of pre-resection CSF shunt in case of signs and symptoms of hydrocephalus is mandatory, although it resolves in the majority of cases. As reported by several studies included in the present review, we suggest CSF shunt also in case of asymptomatic hydrocephalus, whereas it is not indicated without evidence of ventricular dilatation.

Accuracy of splint vs splintless technique for virtually planned orthognathic surgery: A voxel-based three-dimensional analysis.

PURPOSE: This study compared two transferring methods for virtually planned orthognathic surgery - the CAD/CAM intermediate splint and the customized surgical guide with fixation plates. METHODS: This was a prospective clinical study in which participants were consecutively recruited and underwent bimaxillary orthognathic surgery. They were divided into two groups based on the transferring method used. The pre- and postoperative CBCTs were aligned using voxel-based landmark-free registration, and the discrepancies for selected points were compared with the planned displacement of the virtually planned surgery. The maxilla and mandible were analyzed separately, and translation and rotation movements were considered. RESULTS: A total of 16 patients, divided into two groups of eight patients each, were included in this study. The splintless group was significantly more accurate for the translation movement along the x-axes for points A (p = 0.008; mean absolute error 0.527 ± 0.387 for the splint group and 0.137 ± 0.067 for the splintless group) and Ans (p = 0.045; mean absolute error 0.535 ± 0.446 for the splint group and 0.156 ± 0.002 for the splintless group). For the mandible there was a significant difference in accuracy along the x-axes for points B (p = 0.049; mean absolute errors 1.728 ± 1.181 and 0.697 ± 0.519 for the splint and splintless groups, respectively), LL3 (p = 0.049; mean absolute error 1.629 ± 0.912 and 0.851 ± 0.797 for the splint and splintless groups, respectively), LR3 (p = 0.049; mean absolute error 1.711 ± 0.906 and 0.844 ± 0.780 for the splint and splintless groups, respectively), with the splintless group being more accurate. For the rotation the splintless group was significantly more accurate along the y-axes (p = 0.04; mean absolute error 1.62 ± 0.78 and 0.49 ± 0.31 for the splint and splintless groups, respectively) and z-axes (p = 0.04; mean absolute error 0.63 ± 0.45 and 0.17 ± 0.05 for the splint and splintless groups, respectively) for the maxilla, while no significant difference was found for the mandible. CONCLUSIONS: Overall, the customized fixation plate system is more accurate than the intermediate CAD/CAM splint for transferring the virtual plan into the operation room.

Discordant GH and IGF-1 Results in Treated Acromegaly: Impact of GH Cutoffs and Mean Values Assessment.

CONTEXT: Discordant growth hormone (GH) and insulin-like growth factor-1 (IGF-1) values are frequent in acromegaly. OBJECTIVE: To evaluate the impact of different GH cutoffs on discordance rate. To investigate whether the mean of consecutive GH measurements impacts discordance rate when matched to the last available IGF-1 value. DESIGN: Retrospective study. SETTING: Referral center for pituitary diseases. PATIENTS: Ninety acromegaly patients with at least 3 consecutive evaluations for GH and IGF-1 using the same assay in the same laboratory (median follow-up 13 years). INTERVENTIONS: Multimodal treatment of acromegaly. MAIN OUTCOME MEASURES: Single fasting GH (GHf) and IGF-1 (IGF-1f). Mean of 3 GH measurements (GHm), collected during consecutive routine patients' evaluations. RESULTS: At last evaluation GHf values were 1.99 ± 2.79 µg/L and age-adjusted IGF-1f was 0.86 ± 0.44 × upper limit of normality (mean ± SD). The discordance rate using GHf was 52.2% (cutoff 1 µg/L) and 35.6% (cutoff 2.5 µg/L) (P = 0.025). "High GH" discordance was more common for GHf <1.0 µg/L, while "high IGF-1" was predominant for GHf <2.5 µg/L (P < 0.0001). Using GHm mitigated the impact of GH cutoffs on discordance (GHm <1.0 µg/L: 43.3%; GHm <2.5 µg/L: 38.9%; P = 0.265). At receiver-operator characteristic curve (ROC) analysis, both GHf and GHm were poor predictors of IGF-1f normalization (area under the curve [AUC] = 0.611 and AUC = 0.645, respectively). The prevalence of disease-related comorbidities did not significantly differ between controlled, discordant, and active disease patients. DISCUSSION: GH/IGF-1 discordance strongly depends on GH cutoffs. The use of GHm lessen the impact of GH cutoffs. Measurement of fasting GH levels (both GHf and GHm) is a poor predictor of IGF-1f normalization in our cohort.

In Vitro and In Vivo Inhibitory Activity of Limonene against Different Isolates of Candida spp.

Commensal yeast from the genus Candida is part of the healthy human microbiota. In some cases, Candida spp. dysbiosis can result in candidiasis, the symptoms of which may vary from mild localized rashes to severe disseminated infections. The most prevalent treatments against candidiasis involve fluconazole, itraconazole, miconazole, and caspofungin. Moreover, amphotericin B associated with prolonged azole administration is utilized to control severe cases. Currently, numerous guidelines recommend echinocandins to treat invasive candidiasis. However, resistance to these antifungal drugs has increased dramatically over recent years. Considering this situation, new therapeutic alternatives should be studied to control candidiasis, which has become a major medical concern. Limonene belongs to the group of terpene molecules, known for their pharmacological properties. In this study, we evaluated in vitro the limonene concentration capable of inhibiting the growth of yeast from the genus Candida susceptible or resistant to antifungal drugs and its capacity to induce fungal damage. In addition, intravaginal fungal infection assays using a murine model infected by Candida albicans were carried out and the fungal burden, histopathology, and scanning electron microscopy were evaluated. All of our results suggest that limonene may play a protective role against the infection process by yeast from the genus Candida.

Type I Interferons Rule with an Iron Fist.

Pathogens rely on nutrient assimilation, particularly essential metal incorporation, to successfully survive in the host. In this issue of Cell Host & Microbe, Riedelberger et al. (2020) convincingly demonstrate that type I interferons (IFNs-I) promote dysregulation of iron homeostasis in macrophages upon infection with Candida glabrata and exacerbate infection.

A hydrosilver gel for plaque control in adults affected by chronic periodontitis: Effects on the 'red complex' bacterial load. A prospective longitudinal pilot study using polymerase chain reaction analysis.

In subjects affected by chronic periodontitis, the chemical control of plaque is a strategy aiming primarily at controlling infection and bacterial loading. The aim is to evaluate the bacterial loading of the so-called 'red complex' associated with a short-term use of a hydrosilver gel (HSG) by using an in vivo model in adult subjects affected by chronic periodontitis. This prospective short-term clinical trial involved 10 adult volunteers using a 15-day in vivo model. After receiving professional prophylaxis at baseline (t0), each volunteer performed daily applications of HSG at home. After 15 days (t1) from the first application, subgingival plaque samples were collected, and the bacterial loading of species belonging to the red complex was evaluated using polymerase chain reaction (PCR) analyses. The bacterial loading of the red complex showed no statistically significant difference between t0 and t1, although it tended to decrease. HSG can be used at home as an adjunct to domestic oral care because it seems a promising tool, but further studies are needed to involve a larger sample and a longer follow-up.