Very Rapid Improvement in Extended Nitric Oxide Parameters Is Associated With Clinical and Functional Improvement in Patients With Chronic Rhinosinusitis With Nasal Polyps Treated With Dupilumab.

BACKGROUND AND OBJECTIVE: Dupilumab, an anti-IL-4 receptor a monoclonal antibody, was recently approved for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) and moderate-to-severe asthma. Onset of its clinical effects is rapid. CRSwNP is characterized by extended type 2 inflammatory involvement that can be assessed using extended nitric oxide analysis. We investigated whether dupilumab was associated with a rapid improvement in extended nitric oxide parameters, lung function, and clinical outcomes in patients with CRSwNP. METHODS: Consecutive patients with CRSwNP and an indication for dupilumab were evaluated for extended nitric oxide analysis (exhaled, FeNO; bronchial, JawNO; alveolar, CalvNO; nasal, nNO) and lung function 15 and 30 days after initiation of treatment and for clinical outcomes (nasal polyps score [NPS], quality of life questionnaires, visual analog scale [VAS] for the main symptoms, and the Asthma Control Test [ACT]) 30 days after initiation of treatment. RESULTS: We enrolled 33 patients. All extended nitric oxide and lung function parameters improved significantly after 15 days of treatment, remaining stable at 30 days. Scores on the NPS, VAS for the main RSwNP symptoms, quality of life questionnaires, and the ACT improved significantly 30 days after initiation of treatment. CONCLUSION: Dupilumab is associated with very rapid improvement in type 2 inflammation in all airway areas. This is associated with improved lung function and clinical parameters in patients with CRSwNP.

Design of a piezoelectrically actuated hydrocephalus shunt valve.

Hydrocephalus is currently managed by using traditional mechanical passive shunts. Due to their nature, these shunts have fundamental shortcomings including an increase in patient shunt dependency, absence of fault detection, and over drainage due to lack of shunt proactivity. There is a scientific consensus that the way forward to address these issues is through what is termed a smart shunt. The core component of this system is the mechatronic controllable valve. A design of a valve which utilises both the passive nature of the classical valves and the controllability feature of the fully automated valves is presented in this paper. The valve consists of a fluid compartment, a linear spring, and an ultrasonic piezoelectric element. The valve is designed to operate on a 5 V supply, to drain up to 300 mL/h, and it has an operational range between 10 and 20 mmHg. The design produced is considered feasible as it takes into consideration the multiple operation conditions associated with such an implanted system.

Very rapid improvement of extended nitric oxide parameters, associated with clinical and functional betterment, in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) treated with Dupilumab.

BACKGROUND AND OBJECTIVE: Background: Dupilumab, an anti-IL-4 receptor alpha monoclonal antibody, has been recently approved for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) and moderate to severe asthma, demonstrating a rapid onset of clinical effects. CRSwNP is characterized by an extended type-2 inflammatory involvement that can be assessed by extended nitric oxide analysis. Objective: In this study we investigated whether Dupilumab is associated with a rapid improvement in extended nitric oxide parameters, lung function and clinical outcomes in patients with CRSwNP. METHODS: : Consecutive patients with CRSwNP and indication to be treated with Dupilumab were evaluated for extended nitric oxide analysis (exhaled, FENO; bronchial, JawNO and alveolar, CalvNO components; nasal, nNO) and lung function 15 and 30 days after treatment initiation, and for clinical outcomes (nasal polyps score, NPS; quality of life questionnaires; visual analogue scales, VAS, for main symptoms, asthma control test, ACT) after 30 days of treatment initiation. RESULTS: 33 patients were enrolled. All extended nitric oxide and lung function parameters significantly improved after 15 days of treatment remaining stable at 30 days. NPS, VAS for main CRSwNP symptoms, quality of life questionnaires and ACT significantly improved after 30 days of treatment initiation. CONCLUSION: Dupilumab is associated with very rapid improvement in type 2 inflammation in all airway districts and this is associated with improved lung function and clinical parameters in patients with CRSwNP.

Acute alcohol intoxication: a clinical overview.

Abstract: Alcohol is a legal and yet detrimental psychoactive substance, capable of establishing addiction and impacting the physical, mental, social, and economic health of people. Alcohol intake causes a large variety of tissue damages severely impacting the nervous system, digestive and cardiovascular systems and causing oral cavity, oropharyngeal, hypopharyngeal, esophageal, colon-rectal, laryngeal, liver and intrahepatic bile duct, and breast cancers. Alcohol can also play a role in the pathogenesis of diabetes mellitus, cardiomyopathy and hemorrhagic strokes. When drunk during pregnancy it is proved to be responsible for serious damage to fetuses causing a wide range of pathological conditions from miscarriage to Fetal Alcoholic Spectrum Disorder (FASD). Acute ethanol intoxication happens when the amount of alcohol consumed is greater than the disposal capacity of the liver, causing an accumulation of its metabolites displayed by initial dysphoria and disinhibition. Nausea, vomiting, memory loss could happen. Although, it can lead to more serious conditions like impaired speaking, impaired coordination, unstable gait, nystagmus, stupor, or coma. Respiratory depression and death could also happen in such cases. Unfortunately, diagnosis of acute alcohol intoxication is difficult because most of the drinkers deny or minimize their assumption. It is dramatically important to assess when the last intake happened to avoid withdrawal syndrome. Alcohol acute intoxication can be considered a serious harm to health and a relevant issue for healthcare provid-ers working in emergency rooms. Differential diagnosis is crucial to avoid serious outcomes. There is no consensus about therapies for acute intoxication, but supportive and symptomatic treatments were proved effective. The repercussions of alcohol misuse over drinkers' social, familiar, economical and working life enhance the importance of a multidisciplinary approach in such cases.

Pre-operative interventional radiology: could it have a role before complex laparoscopic surgery?

ABSTRACT: Bleedings occurring during a surgical intervention can be caused by haemostatic defects, but they are generally due to ineffective local haemostasis. Current coagulation systems may not be sufficient to achieve a good haemostasis, causing, at the same time, tissue dama-ge. Furthermore, the availability of such devices does not eliminate difficulties linked to the isolation of vessels, a crucial step of surgical procedures that require the removal of an organ or part of it, in case of inflammation or neoplasm. This difficulty is even more evident, and weighs more on operative times, when the surgeon engages with video-assisted surgery, where anatomical structures are difficult to detect and the manoeuvres of dissection and separation become more complex. The use of pre-operative radio-guided embolization of organ main arterial vessels with different embolic agents, could represent a great advantage, especially for mini-invasive procedures, such as laparoscopy in patients with high bleeding risk.

Colour Doppler-guided Haemorrhoidal Artery Ligation: a possible evolution of Transanal Haemorrhoidal Dearterialisation.

INTRODUCTION: Haemorrhoids are a very common disease, with a great economic burden. Many treatments have been developed for trying to solve the problem, being the standard not yet found. In 1995, Doppler-guided haemorrhoidal artery ligation was introduced, aiming to reduce postoperative pain and complications. In this work, an evolu-tion of the aforementioned surgical technique was described. MATERIALS AND METHODS: 183 patients treated with standard Doppler-Guided Haemorrhoidal Artery Ligation were statistically compared with 225 patients dealt with Colour Doppler-Guided Haemorrhoidal Artery Ligation. The procedures were performed under local anaes-thesia with patients in lithotomy position. A special proctoscope and a dedicated Colourdoppler US probe were employed in the second group. Superior haemorrhoidal artery terminal branches were con-secutively ligated according to provided technique in the first group and under vision in the second. In all cases, each ligation was followed by mucopexy. RESULTS: No significant differences between the two groups, in terms of post-operative pain, early complications (bleeding, urinary retention, incontinence) or patient satisfaction, were demonstrated. Recurrence rate was significantly higher in patients treated with stan-dard DG-HAL. No late complications (after one-year follow-up) were registered in both groups. CONCLUSIONS: Colour Doppler-Guided Haemorrhoidal Artery Li-gation represents an ideal management for 1-day surgery, and fulfils the requirements of minimally invasive surgery in patients with III-IV grade haemorrhoids. The absence of complications and the evidence of significant wellness of patients are the best advantages. Colour Doppler-Guided Haemorrhoidal Artery Ligation is a safe and easy procedure with good results and a very short-time training. It could be considered an easy and reliable method to treat symptomatic haemorrhoids.

Tertiary hyperparathyroidism: a review.

ABSTRACT: Tertiary hyperparathyroidism (HPT III) occurs when an excess of parathyroid hormone (PTH) is secreted by parathyroid glands, usually after longstanding secondary hyperparathyroidism. Some authorities reserve the term for secondary hyperparathyroidism that persists after successful renal transplantation. Long-standing chronic kidney disease (CKD) is associated with several metabolic disturbances that lead to increased secretion of PTH, including hyperphosphatemia, calcit-riol deficiency, and hypocalcaemia. Hyperphosphatemia has a direct stimulatory effect on the parathyroid gland cell resulting in nodular hyperplasia and increased PTH secretion. Prolonged hypocalcaemia also causes parathyroid chief cell hyperplasia and excess PTH. Af-ter correction of the primary disorder CKD by renal transplant, the hypertrophied parathyroid tissue fails to resolute, enlarge over and continues to oversecrete PTH, despite serum calcium levels that are within the reference range or even elevated. They also may become resistant to calcimimetic treatment. The main indication for treatment is persistent hypercalcemia and/or an increased PTH, and the primary treatment is surgery. Three procedures are commonly performed: total parathyroidectomy with or without autotransplantation, subtotal parathyroidectomy, and limited parathyroidectomy. It is important to remove superior parts of thymus as well. The most appropriate surgical procedure, whether it be total, subtotal, or anything less than subtotal including "limited" or "focused" parathyroidectomies, continues to be unclear and controversial. Surgical complications are rare, and para-thyroidectomy appears to be a safe and feasible treatment option for HPT III.

Scar endometriosis: not a rare cause for a painful scar.

CONCLUSION: High suspicion of scar endometriosis are painful no-dule in the abdominal scar. Wide surgical excision is the treatment of choice. INTRODUCTION: Endometriosis has been described as the presence of endometrial tissue outside uterine cavity. Scar endometriosis (SE) is a rare disease reported in 0.03-1.08% of women following gynaecologic surgery. In our retrospective observational cohort study we studied anamnesis, symptoms, surgical procedures and outcomes linked to scar endometriosis in our medical experience from 2004 to 2018. METHODS: We reviewed the medical records of 46 patients with a histopathological diagnosis of SE. All patients had a history of at least one previous caesarean section (n=46, 100%). Forty-two patients (91,3%) complained gradually growing nodular abdominal mass near or adjacent to caesarean incision scar, while only 4 patients (8,6%) complained aspecific abdominal pain. Ultrasound scan was performed in all patients (n=46, 100%) and mean size of the nodules at US was 26,8 ± 13,8 mm. RESULTS: All patients underwent surgery. Seven patients (15,2%) needed mesh implantation, while 39 patients (84,8%) underwent local resection with reconstruction of muscle fascia. Mean follow-up was 31,6 ± 14 months and no patients reported local recurrence of disease.

Epi-off-lenticule-on corneal collagen cross-linking in thin keratoconic corneas.

PURPOSE: To evaluate the safety and efficacy of corneal collagen cross-linking (CXL) performed on overlaying a corneal lenticule to thin recipient corneas of progressive keratoconus (KC) patients. METHODS: In this study were enrolled eyes of patients affected by progressive KC with a minimum corneal thickness less than 400 µm, after overlaying a lenticule of human corneal stroma prepared with the femtosecond laser. The lenticules used were 100 µm thick and of 8.5 mm diameter in all the cases. Both the host cornea and the lenticules were subjected to epithelial debridement. CXL was carried out according to the standard protocol. Visual acuity, refraction, slit-lamp examination, endothelial cell density, pachymetry and keratometry, anterior segment tomography (AS-OCT) and confocal microscopy were evaluated preoperatively and at 1, 3, 6 and 12 months postoperatively. RESULTS: CXL was performed in 10 eyes of 8 patients (main age 23), corneal thickness range 379-414 µm, mean 387.6 µm. One patient was lost at follow-up. In all other cases, visual acuity and the endothelial cell density remained stable over a 12-month follow-up. Preoperative mean K1 and mean K2 were 46.91 ± 1.9 and 50.75 ± 2.93, respectively, and at 12 months mean K1 was 47.36 ± 2.66 and mean K2 50.53 ± 3.35. The AS-OCT clearly showed a demarcation line in all patients at 1, 3 (mean depth 283 µm and 267 µm, respectively) and in some cases at 6 months. Reduced keratocyte density and stromal oedema were observed immediately up to 1 month after treatment, while a slight subepithelial haze was present at 1-month and completely disappeared by 6 months. CONCLUSION: This new technique seems to offer a therapeutic opportunity for young patients suffering from progressive KC with very thin corneas, in which the standard treatment is not indicate, and delay or avoid the need for a corneal transplant.

The role of ozonized oil and a combination of tobramycin/dexamethasone eye drops in the treatment of viral conjunctivitis: a randomized clinical trial.

PURPOSE: To determine whether topical tobramycin 0.3%/dexamethasone 0.1% plus ozonized oil eye drops reduces clinical signs and infectious viral titers of presumed viral conjunctivitis more than tobramycin/dexamethasone eye drops alone. METHODS: Prospective, single-blind, randomized, parallel-groups trial. Eighty patients with a clinical diagnosis of presumed viral conjunctivitis were randomizedly divided into two treatment groups: a study group and a control group, 40 for each group. Patients in the study group received topical tobramycin 0.3%/dexamethasone 0.1% eye drops, plus ozonized oil eye drops, both four times daily; patients in the control group received only topical tobramycin 0.3%/dexamethasone eye drops four times daily. The treatment was for seven days in both groups. Swabs were taken from the conjunctival fornix for adenovirus PCR analysis on the day of recruitment and at seven days follow-up. Clinical signs were also recorded on the day of recruitment and at follow-up examination: the main outcomes were conjunctival injection and conjunctival chemosis, graded on a 4-point clinical scale, presence or absence of superficial punctate keratitis and subepithelial corneal infiltrates. RESULTS: No statistically significant difference was reached in adenoviral infection negativization between the two groups, although the study group showed a higher number of PCR negative results at seven days follow-up. PCR real time detected adenoviral infection in 17 of 24 patients on the day of recruitment and it was positive in 4 patients on the seventh day (viral positivity reduction of 76%). In the control group PCR was positive for adenovirus in 18 of 24 patients on the day of recruitment and in 7 patients at seven days follow-up (reduction of 61%). There was statistically significant difference on conjunctival clinical signs between the study and control groups. Significant difference was also found on superficial punctate keratitis resolution between the study and the control group. In the former superficial punctate keratitis was detected in 14 eyes on the first day and in 5 eyes after seven days while in the latter superficial punctate keratitis was found in 124 eyes on the first day and in 6 eyes on the seventh day. No difference was found in subepithelial corneal infiltrates appearance between the two groups. CONCLUSIONS: The use of ozonized-oil containing eye drops in combination with topical tobramycin 0.3%/dexamethasone 0.1% eye drops four times daily seems to reduce the signs of conjunctivitis, and the duration of viral infection, although it does not affect the subepithelial corneal infiltrates appearance.

The role of cytokines in head and neck squamous cell carcinoma: A review.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, accounting for approximately 6% of all cancer cases and responsible for an estimated 1-2% of all cancer deaths. Much research evidence has accumulated in the recent years on the changes in the expression of pro-inflammatory and, to a lesser extent, anti-inflammatory cytokines, that (i) may have a role in the malignant transformation of HNSCC, (ii) may be used as diagnostic markers in the sera of patients because of their excessive production by the tumor cells and (iii) may act as possible immunotherapeutic targets. Among pro-inflammatory cytokines, interleukin-8 (IL--8) has been reported to have an important role in cancer invasion, angiogenesis and metastasis. Recent studies have shown an increased concentration of IL--8 in patients with HNSCC and a positive association with lymph node metastasis and tumor classification, although IL--8 was not significantly associated with shorter overall survival and cancer progression-free survival. Additional evidence on the pathological mechanism of origin, invasion, and metastasis of HNSCC, as well as a better understanding of the implications of cytokines, chemokines and growth factors, are of paramount importance for the advancement of research in head and neck oncology.

Pancoast tumour: current therapeutic options.

BACKGROUND: Pancoast's syndrome is caused by malignant neoplasm of superior sulcus of the lung which produces destructive lesions of thoracic inlet and comes along with the involvement of brachial plexus and stellate ganglion. Computed tomography (CT) or magnetic resonance imaging (MRI) scans can detect early lesions otherwise missed by routine radiographs and can also define the local extent or metastatic progression of the disease. Protocols involving combinations of irradiation, chemotherapy, and surgery are currently being under investigation to determine the best management. AIMS: This work reviewed the current diagnostic and therapeutic approaches to Pancoast's tumors. DISCUSSION: Patients with lung superior sulcus carcinoma should be considered for surgery only after an appropriate diagnostic assessment. The perfect candidate for surgery should have a confined to the chest disease with T3N0M0 staging. Inoperable patient with severe pain after irradiation therapy may benefit from palliative surgical resection. Medical therapy plays only a secondary role in lung cancers, patients with disseminated lung cancer might require palliative treatment and medical management of paraneoplastic syndrome symptoms. Following surgery, radiation and chemotherapy may improve local and systemic control by addressing individual adverse findings. CONCLUSIONS: The cooperation of surgeons, clinicians and radiologists represents the gold standard today and a multidisciplinary approach is essential to achieve the best outcome possible. Further studies are advisable in order to define the best surgical approach and the real advantage of mini-invasive surgery by comparison with open surgery.

Correlation of central and peripheral keratometric parameters after corneal collagen cross-linking in keratoconus patients.

PURPOSE: To evaluate the difference in the central and peripheral keratometric parameters in patients with keratoconus after corneal collagen cross-linking (CXL). METHODS: Forty-eight eyes of 32 patients (18 males, 16-28 years) affected by progressive keratoconus in different stages of evolution underwent CXL using the standard epithelium-off protocol. Corneal thickness and corneal curvature before CXL and after 6 and 12 months using the Sirius tomographer were analyzed. The values of the mean corneal thickness at the corneal apex (CAT), center of the pupil (PCT), thinnest point (CTTL) and along concentric circles of 2, 4, 6, 8, 8.5, 9, 9.5 and 10 mm diameter were evaluated; the values of the mean curvature at the corneal apex and at the points in which the inferior, superior, nasal and temporal meridians crossed the above-mentioned concentric circles were also evaluated. RESULTS: The mean preoperative values for CAT, PCT and CTTL were 461.4 ± 30.3, 475.3 ± 30.5 and 441 ± 32.0, respectively. The values after 12 months of CXL were 444.6 ± 36.2, 451.6 ± 36.7 and 418.2 ± 41.4. The peripheral corneal thickness at the eight points ranged from 479 to 733 preoperatively. At 12-month post-CXL, the values ranged from 444.6 to 734.1. The mean posterior curvature from apex to periphery ranged from - 4.5 to - 9.1 days preoperatively and from - 4.5 to - 9.2 days at 12 months. These were not statistically significant (ANOVA and unpaired T test). CONCLUSIONS: Our data suggest that CXL over an 8-mm zone can stabilize the peripheral cornea. Longer-term follow-up studies on the peripheral cornea after CXL will provide useful information.

Genetic landscape of ultra-stable chronic lymphocytic leukemia patients.

Background: Chronic lymphocytic leukemia (CLL) has a heterogeneous clinical course. Beside patients requiring immediate treatment, others show an initial indolent phase followed by progression and others do not progress for decades. The latter two subgroups usually display mutated IGHV genes and a favorable FISH profile. Patients and methods: Patients with absence of disease progression for over 10 years (10-34) from diagnosis were defined as ultra-stable CLL (US-CLL). Forty US-CLL underwent extensive characterization including whole exome sequencing (WES), ultra-deep sequencing and copy number aberration (CNA) analysis to define their unexplored genetic landscape. Microarray analysis, comparing US-CLL with non-US-CLL with similar immunogenetic features (mutated IGHV/favorable FISH), was also carried out to recognize US-CLL at diagnosis. Results: WES was carried out in 20 US-CLL and 84 non-silent somatic mutations in 78 genes were found. When re-tested in a validation cohort of 20 further US-CLL, no recurrent lesion was identified. No clonal mutations of NOTCH1, BIRC3, SF3B1 and TP53 were found, including ATM and other potential progression driving mutations. CNA analysis identified 31 lesions, none with known poor prognostic impact. No novel recurrent lesion was identified: most cases showed no lesions (38%) or an isolated del(13q) (31%). The expression of 6 genes, selected from a gene expression profile analysis by microarray and quantified by droplet digital PCR on a cohort of 79 CLL (58 US-CLL and 21 non-US-CLL), allowed to build a decision-tree capable of recognizing at diagnosis US-CLL patients. Conclusions: The genetic landscape of US-CLL is characterized by the absence of known unfavorable driver mutations/CNA and of novel recurrent genetic lesions. Among CLL patients with favorable immunogenetics, a decision-tree based on the expression of 6 genes may identify at diagnosis patients who are likely to maintain an indolent disease for decades.

Colorectal cancer in patients with type 2 diabetes mellitus: a single-center experience.

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of colorectal cancer (CRC). The aim of the study is to evaluate the prevalence of CRC in a cohort of Caucasian patients with T2DM and the association with other variables previously known to be related with increased risk of CRC. We retrospectively evaluated the data of 741 consecutive Caucasian patients with T2DM who underwent colonoscopic screening in our tertiary referral center. A control cohort of 333 patients with thyroid disease was selected to evaluate the difference in the incidence of CRC. At a median follow-up of 132.5 months (range 33.3-175.7), 67 cases of cancer (prevalence 9%) occurred; among these, 14 cases of CRC were reported (prevalence 1.88%) among the diabetic patients, while only two case (one of these was a CRC) (overall prevalence 0.006%, prevalence of CRC 0.003%) occurred in the control group; the difference between the prevalence of CRC was statistically significant (chi-square 4.21, p=0.04). The median duration of T2DM to CRC diagnosis was 168 months (range 12-768). At the univariate analysis, older age (p=0.001, r 0.138) and diabetes duration (p=0.001, r 0.138) were related to higher risk of cancer, while metformin seems to be protective towards cancer (p=0.07, r -0.098). In the subset of patients with CRC, the age (RR = 2.25; 95% CI: 0.30 - 17.31; p less than 0.001), the diabetes duration (RR = 1.93; 95% CI: 0.25 – 14.77; p = 0.001) and the sulphonylureas treatment (RR = 2.33; 95% CI: 0.78 – 7.38; p = 0.007) were independently correlated with CRC. In our study, the prevalence of CRC in the cohort of patients with T2DM was higher compared to that from the National Tumor Register in 2010 (0.5%). Furthermore, we could speculate that sulphonylureas may play a role in CRC carcinogenesis impairing the physiological insulin secretion.