Laparoscopic Heller-Dor myotomy in elderly achalasia patients: a single center experience with PSM analysis.

INTRODUCTION: Achalasia is a rare esophageal motility disorder of unknown etiology. With the ageing of the general population, treatment in elderly patients has become increasingly common; however, the gold standard treatment in this population remains unclear. The aim of this study was to evaluate the outcomes of laparoscopic Heller-Dor myotomy (LHM) in geriatric patients. MATERIAL AND METHODS: In this study, consecutive achalasia patients undergoing LHM at the University Hospital 'Federico II' of Naples from November 2018 to November 2022 were prospectively enrolled. Patients were divided into two groups based on their age at intervention: elderly (≥70 years) and younger (<70 years). The two study groups were compared by minimizing the different distribution of covariates through a propensity score matching analysis (PSM). RESULTS: In both populations, there was a significant improvement in terms of manometric parameters and symptoms after surgery. After applying one-on-one PSM, we obtained a total population of 48 achalasia patients divided into two groups (24 patients each). No significant differences were found in terms of demographic characteristics as well as preoperative and intraoperative variables between two groups. At 12 months from surgery, integrated relaxation pressure (IRP) was significantly lower in patients ≥ 70 years (p = 0.032), while younger patients scored significantly less at the post-operative Eckardt score (p = 0.047). CONCLUSIONS: Laparoscopic Heller-Dor myotomy is a safe and effective treatment even in elderly patients with rapid post-operative recovery, improvement of symptoms and manometric parameters.

Robotic Surgery in Achalasia: State of the Art.

Introduction: Achalasia is a rare primary esophageal disorder characterized by impaired functioning of the lower esophageal sphincter. The goal of treatment is to reduce symptoms and improve the quality of life. The gold standard of surgical approach is Heller-Dor myotomy. The aim of this review is to describe the use of robotic surgery in patients with achalasia. Methods: The literature review was performed by searching on PubMed, Web of Science, Scopus and EMBASE for all studies on robotic surgery for achalasia, published from January 1, 2001, to December 31, 2022. We focused our attention on randomized controlled trials (RCTs), metaanalysis, systematic reviews, and observational studies on large cohorts of patients. Furthermore, we have identified relevant articles from the reference list. Conclusions: Taking into consideration our review and experience, RHM with partial fundoplication is safe, efficient, comfortable for the surgeon and characterized by a reduction of the intraoperative perforation rate of the esophageal mucosa. This approach may represent the future for the surgical treatment of achalasia especially with a reduction in costs.

Pentamidine niosomes thwart S100B effects in human colon carcinoma biopsies favouring wtp53 rescue.

S100B protein bridges chronic mucosal inflammation and colorectal cancer given its ability to activate NF-kappaB transcription via RAGE signalling and sequestrate pro-apoptotic wtp53. Being an S100B inhibitor, pentamidine antagonizes S100B-wtp53 interaction, restoring wtp53-mediated pro-apoptotic control in cancer cells in several types of tumours. The expression of S100B, pro-inflammatory molecules and wtp53 protein was evaluated in human biopsies deriving from controls, ulcerative colitis and colon cancer patients at baseline (a) and (b) following S100B targeting with niosomal PENtamidine VEhiculation (PENVE), to maximize drug permeabilization in the tissue. Cultured biopsies underwent immunoblot, EMSA, ELISA and biochemical assays for S100B and related pro-inflammatory/pro-apoptotic proteins. Exogenous S100B (0.005-5 µmol/L) alone, or in the presence of PENVE (0.005-5 µmol/L), was tested in control biopsies while PENVE (5 µmol/L) was evaluated on control, peritumoral, ulcerative colitis and colon cancer biopsies. Our data show that S100B level progressively increases in control, peritumoral, ulcerative colitis and colon cancer enabling a pro-inflammatory/angiogenic and antiapoptotic environment, featured by iNOS, VEGF and IL-6 up-regulation and wtp53 and Bax inhibition. PENVE inhibited S100B activity, reducing its capability to activate RAGE/phosphor-p38 MAPK/NF-kappaB and favouring its disengagement with wtp53. PENVE blocks S100B activity and rescues wtp53 expression determining pro-apoptotic control in colon cancer, suggesting pentamidine as a potential anticancer drug.

Completeness of total mesorectum excision of laparoscopic versus robotic surgery: a review with a meta-analysis.

BACKGROUND: TME has revolutionized the surgical management of rectal cancer, and since the introduction of robotic TME (RTME), many reports have shown the feasibility and the safety of this approach. However, concerns persist regarding the advantages of robotic in surgery for the completeness of TME. The aim of this review is to compare robotic versus laparoscopic total mesorectal excision (TME) in rectal cancer, focusing on the completeness of TME. METHODS: A systematic search was performed in the electronic databases for all available studies comparing RTME versus conventional laparoscopic LTME with declared grade of mesorectum excision. Data regarding sample size, clinical and demographic characteristics, number of complete, nearly complete, and incomplete TME were extracted. Primary outcome was the number of complete TME in robotic and laparoscopic procedures. Secondary outcomes were the numbers of nearly complete and incomplete TME in robotic and laparoscopic rectal resections. RESULTS: Twelve articles were included in the final analysis. Complete TME was reported by all authors, involving 1510 procedures, showing a significant difference in favor of robotic surgery (OR = 1.83, 95% CI 1.08-3.10, p = 0.03). Nearly complete and incomplete TME showed no significant difference between the procedures. Meta-regression analysis showed that none of patients' and tumors' characteristics significantly impacted on complete TME. CONCLUSIONS: Our results underline that the robotic approach to rectal resection is the better way to obtain a complete TME. However, it is mandatory that randomized clinical trials should be performed to assess definitively if robotic minimally invasive surgery is better than a laparoscopic resection.

Incidence and risk factors of portomesenteric venous thrombosis after colorectal surgery for cancer in the elderly population.

BACKGROUND: Although it is known that portomesenteric venous thrombosis (PMVT) is associated with total colectomy and proctocolectomy in young patients with inflammatory bowel disease, little is known about incidence and risk factors of PMVT among the elderly population undergoing colorectal surgery for cancer. METHODS: Data of elderly patients (> 70 years) undergoing surgery for colorectal cancer were retrospectively registered. The occurrence of PMVT was correlated with the patients' characteristics and operative variables. Data collected included age, sex, obesity, ASA score, tumor degree, type of surgical resection, surgical approach (laparoscopic or open), and duration of surgery (from skin incision to the application of dressings). RESULTS: A total of 137 patients > 70 years who underwent surgery for colorectal cancer and developed an acute intraabdominal process with suggestive symptoms, needing a CT scan, were included. Three of these patients (2.1%) had portomesenteric venous thrombosis during the study period, which was proved with CT scan. There were no significant patients' characteristics or operative variables between patients with or without the occurrence of PMVT after surgery. Of interest, only operative time was significantly higher in patients with PMVT after surgery (256 ± 40 vs 140 ± 41, p < 0.001). CONCLUSIONS: PMVT as a cause of abdominal pain after colorectal surgery for cancer in the elderly population is uncommon. An index of suspicion for PMVT in an elderly postoperative colorectal cancer patient with sudden onset of abdominal pain must be maintained.

Laparoscopic hepatectomy for HCC in elderly patients: risks and feasibility.

BACKGROUND: Laparoscopic liver resection (LLR) appears to be safe and effective as open liver resection (OLR) for hepatocellular carcinoma (HCC). However, studies comparing LLR with ORL in elderly patients are limited. The purpose of this study is to compare the clinical outcomes of LLR versus OLR for HCC in elderly patients. METHODS: A retrospective analysis was made comparing laparoscopic (n = 11) and open (n = 18) liver resections in elderly patients performed at the University of Naples "Federico II" between January 2010 and December 2014. Demographic data, operative and postoperative outcomes were analyzed. RESULTS: Demographic and tumor characteristics of laparoscopic and OLRs were similar. There were also no significant differences in operating room time. Patients undergoing OLR had increased rate of minor complications (33 vs. 0%), longer lengths of stay (6 vs. 3 days) and higher blood loss (310 ± 84 vs. 198 ± 34 ml). There were no significant differences in major complication rates or 90-day mortality. DISCUSSION: LLR is safe and feasible as OLR for treatment of HCC in selected elderly patients.

Laparoscopic distal pancreatectomy in elderly patients: is it safe?

BACKGROUND: Laparoscopic distal pancreatectomy (LDP) appears to be safe and effective as open distal pancreatectomy (ODP) for benign or borderline malignant lesion. However, studies comparing LDP with ODP in elderly patients are limited. The purpose of this study is to compare the clinical outcomes of these two several approaches in elderly patients. METHODS: A retrospective analysis was carried out by comparing laparoscopic (n = 7) and open (n = 15) distal pancreatectomy in elderly patients performed at the University of Naples "Federico II" and University of Perugia between January 2012 and December 2015. Demographic data, operative and postoperative outcomes were analyzed. RESULTS: Demographic and tumor characteristics of laparoscopic and ODP were similar. There were also no significant differences in operating room time. Patients undergoing LDP had lower blood loss, first flatus time, diet start time and postoperative hospital stay. There were no significant differences in complication rates or 90-day mortality. DISCUSSION: LDP is safe and feasible as ODP in selected elderly patients.

Artificial intelligence applied to laparoscopic cholecystectomy: what is the next step? A narrative review.

Artificial Intelligence (AI) is playing an increasing role in several fields of medicine. AI is also used during laparoscopic cholecystectomy (LC) surgeries. In the literature, there is no review that groups together the various fields of application of AI applied to LC. The aim of this review is to describe the use of AI in these contexts. We performed a narrative literature review by searching PubMed, Web of Science, Scopus and Embase for all studies on AI applied to LC, published from January 01, 2010, to December 30, 2023. Our focus was on randomized controlled trials (RCTs), meta-analysis, systematic reviews, and observational studies, dealing with large cohorts of patients. We then gathered further relevant studies from the reference list of the selected publications. Based on the studies reviewed, it emerges that AI could strongly improve surgical efficiency and accuracy during LC. Future prospects include speeding up, implementing, and improving the automaticity with which AI recognizes, differentiates and classifies the phases of the surgical intervention and the anatomic structures that are safe and those at risk.

Artificial intelligence in screening and diagnosis of surgical diseases: A narrative review.

Artificial intelligence (AI) is playing an increasing role in several fields of medicine. It is also gaining popularity among surgeons as a valuable screening and diagnostic tool for many conditions such as benign and malignant colorectal, gastric, thyroid, parathyroid, and breast disorders. In the literature, there is no review that groups together the various application domains of AI when it comes to the screening and diagnosis of main surgical diseases. The aim of this review is to describe the use of AI in these settings. We performed a literature review by searching PubMed, Web of Science, Scopus, and Embase for all studies investigating the role of AI in the surgical setting, published between January 01, 2000, and June 30, 2023. Our focus was on randomized controlled trials (RCTs), meta-analysis, systematic reviews, and observational studies, dealing with large cohorts of patients. We then gathered further relevant studies from the reference list of the selected publications. Based on the studies reviewed, it emerges that AI could strongly enhance the screening efficiency, clinical ability, and diagnostic accuracy for several surgical conditions. Some of the future advantages of this technology include implementing, speeding up, and improving the automaticity with which AI recognizes, differentiates, and classifies the various conditions.

Day-surgery inguinal hernia repair in the elderly: single centre experience.

BACKGROUND: Inguinal hernioplasty is well established as a day-surgery procedure, our purpose is to assess the safeness of this approach in elderly patients. METHODS: A total of 292 inguinal hernioplasty were performed between June 2009 and February 2013. Patients were divided into 3 groups depending on the age and postoperative complications were compared in these groups. RESULTS: Despite of a large number of higher risk (ASA 3-4) patients and a higher rate of comorbidity in older patients, unplanned admission postoperative, symptoms and complications were comparable with those for the younger patients. CONCLUSIONS: Ambulatory surgery is feasible also in older patients. Age, comorbidity and higher ASA risk should not be a barrier to elective day surgery.

Emergency groin hernia repair: implications in elderly.

BACKGROUND: Groin hernia is one of the most frequently encountered pathologies occurring in old age and it is often the cause of emergency procedures. In our study we evaluate the impact of emergency procedures in over 75 patients compared to younger patients. METHODS: We conducted a retrospective study about patients who underwent emergency hernioplasty between September 2007 and January 2013. Bilateral hernias and recurrences were excluded. We divided patients into two groups by age (under and over 75 years old) and then analyzed the early postoperative surgical complications. RESULTS: A total of 48 patients were enrolled, 18 were included in under 75 group and 30 in over 75. In the older group we found a higher rate of comorbidity and also a significant higher rate of postoperative complications. Two patients of over 75 group died. CONCLUSIONS: Our data suggests that a quick diagnosis and elective surgical procedures are desirable in order to avoid the complications that occur in emergency operations.

Local anesthesia for treatment of hernia in elder patients: Levobupicavaine or Bupivacaine?

BACKGROUND: Inguinal hernia is one of the most common diseases in the elderly. Treatment of this pathology is exclusively surgical and relies almost always on the use of local anesthesia. While in the past hernia surgery was carried out mainly by general anesthesia, in recent years there has been growing emphasis on the role of local anesthesia. METHODS: The aim of our study was to compare intra-and postoperative analgesia obtained by the use of levobupivacaine to the same obtained by bupivacaine. Bupivacaine is one of the main local anesthetics used in the intervention of inguinal hernioplasty. Levobupivacaine is an enantiomer of racemic bupivacaine with less cardiotoxicity and neurotoxicity. The study was conducted from March 2011 to March 2013. We collected data of eighty patients, male and female, aged between 65 and 86 years, who underwent inguinal hernioplasty with local anesthesia. RESULTS: Evaluation of intra-operatively pain shows that minimal pain is the same in both groups. Mild pain was more frequent in the group who used levobupivacaine. Moderate pain was slightly more frequent in the group who used bupivacaine. Only one reported intense pain. Two drugs seem to have the same effect at a distance of six, twelve, eighteen and twentyfour hours. Bupivacaine shows a significantly higher number of complications, as already demonstrated by previous studies. Degree of satisfaction expressed by patients has been the same in the two groups. Levobupivacaine group has shown a greater request for paracetamol while patients who experienced bupivacaine have showed a higher request of other analgesics. CONCLUSIONS: Clinical efficacy of levobupivacaine and racemic bupivacaine are actually similar, when used under local intervention of inguinal hernioplasty. In the field of ambulatorial surgery our working group prefers levobupivacaine for its fewer side effects and for its easy handling.

Upper extremity vein thrombosis: an alert symptom of breast cancer in elderly patients. Experience on personal casuistry and review of the literature.

BACKGROUND: Breast Cancer in elderly patients is a significant health problem representing an important source of morbidity and mortality. Although the most common presentation is the presence of a palpable lump there may be, especially in the elderly population, rare clinical manifestations such as thromboembolic events that often involve the upper limbs. METHODS: We retrospectively reviewed a ten year clinical casuistry of patients with Breast Cancer who presented for an initial diagnosis of upper extremity vein thrombosis. RESULTS: 13 patients with initial diagnosis of upper limbs vein thrombosis (1M-12 F; age range 48-76; median age 70 years) resulted affected from Breast Cancer. The diagnosis of vein thrombosis represented the first clinical manifestation related to thier malingancy. All patients of our casuistry had positive ER/PR receptor status. CONCLUSIONS: A case of upper vein extrmity thrombosis in an elderly patient should prompt a high index of suspicion for breast malignancy in order to avoid diagnostic delay that may retard appropriate treatment.

Cyanoacrylate in Colorectal Surgery: Is It Safe?

Anastomotic leakage (AL) of a gastrointestinal (GI) anastomosis continues to be an important complication in GI surgery. Since its introduction more than 60 years ago, Cyanoacrylate (CA) has gained popularity in colorectal surgery to provide "prophylaxis" against AL. However, although in surgical practice it is increasingly used, evidence on humans is still lacking. The aim of this study is to analyze in humans the safety of CA to seal colorectal anastomosis. All consecutive patients from Jannuary 2022 through December 2022 who underwent minimally invasive colorectal surgery were retrospectively analyzed from a prospectively maintained database. Inclusion criteria were a histological diagnosis of cancer, a totally minimally invasive procedure, and the absence of intraoperative complications. 103 patients were included in the study; N-butyl cyanoacrylate with metacryloxisulfolane (Glubran 2®) was used to seal colorectal anastomosis, no adverse reactions to CA or postoperative complications related to inflammation and adhesions occurred; and only one case of AL (0.9%) was recorded. We can consider this study an important proof of concept on the safety of CA to seal colorectal anastomosis. It opens the possibility of starting prospective and comparative studies in humans to evaluate the effectiveness of CA in preventing colorectal AL.

GERD in elderly patients: surgical treatment with Nissen-Rossetti laparoscopic technique, outcome.

BACKGROUND: The gastro-esophageal reflux disease (GERD) is one of the most frequent disease of the upper gastro-entheric tract. Surgical treatment is reserved to selected patients, affected by severe forms of disease and/or without compliance to medical therapy.In 95%-60% of the patients submitted to surgical antireflux intervention, a notable improvement of the quality of life is observed.Functional evaluations performed on pre and post--surgical pHmetric and manometric examination have provided new acquisitions about improvements in the restoration of anatomical and functional integrity of the esophagus-gastric antireflux barrier. METHODS: 45 elderly patients with GERD were recruited in a 27 months period. All patients were subjected to laparoscopic Nissen-Rossetti 360° fundoplication. The subjects had a pre-surgical evaluation with:• 24 hours pHmetry,• esophageal manometry,The same evaluation was repeated 1 month and 6 months after surgical intervention. RESULTS: In our series all patients get benefit from surgical treatment, with an improvement of pHmetric and manometric parameters and a regression of complications of GERD such as Barrett's metaplasia. In 8.33% of patients a PPI therapy was necessary, after the surgical intervention, to control symptoms. CONCLUSIONS: The role of surgery in GERD concerns selected patients. Nissen-Rossetti mini-invasive approach is performed with an acceptable percentage of complications (3%-10%). This technique is associated with a good control of GERD symptoms in a short and middle term and with an improvement of functional parameters, such as pHmetric and manometric.

Comparative study between Levobupivacaine and Bupivacaine for hernia surgery in the elderly.

BACKGROUND: The inguinal hernia is one of the most common diseases in the elderly. Treatment of this type of pathology is exclusively surgical and relies almost always on the use of local anesthesia. While in the past hernia surgery was carried out mainly by general anesthesia, in recent years there has been growing emphasis on the role of local anesthesia. METHODS: The aim of our study was to compare intra-and postoperative analgesia obtained by the use of levobupivacaine compared with that of bupivacaine. Bupivacaine is one of the main local anesthetics used in the intervention of inguinal hernioplasty. Levobupivacaine is an enantiomer of racemic bupivacaine with less cardiotoxicity and neurotoxicity. The study was conducted from April 2010 to May 2012. We collected data of forty male patients, aged between 73 and 85 years, who underwent inguinal hernioplasty with local anesthesia for the first time. RESULTS: Minimal pain is the same in both groups. Mild pain was more frequent in the group who used bupivacaine, moderate pain was slightly more frequent in the group who used levobupivacaine, and the same for intense pain. It is therefore evident how Bupivacaine is slightly less preferred after four and twenty four hours, while the two drugs seem to have the same effect at a distance of twelve and forty-eight hours. Bupivacaine shows a significantly higher number of complications, as already demonstrated by previous studies. The request for an analgesic was slightly higher in patients receiving levobupivacaine. CONCLUSIONS: After considering all these elements, we can conclude that the clinical efficacy of levobupivacaine and racemic bupivacaine are essentially similar, when used under local intervention of inguinal hernioplasty.

Morpho-functional gastric pre-and post-operative changes in elderly patients undergoing laparoscopic cholecystectomy for gallstone related disease.

BACKGROUND: Cholecystectomy, gold standard treatment for gallbladder lithiasis, is closely associated with increased bile reflux into the stomach as amply demonstrated by experimental studies. The high prevalence of gallstones in the population and the consequent widespread use of surgical removal of the gallbladder require an assessment of the relationship between cholecystectomy and gastric mucosal disorders.Morphological evaluations performed on serial pre and post - surgical biopsies have provided new acquisitions about gastric damage induced by bile in the organ. METHODS: 62 elderly patients with gallstone related disease were recruited in a 30 months period. All patients were subjected to the most appropriate treatment (Laparoscopic cholecystectomy). The subjects had a pre-surgical evaluation with:• dyspeptic symptoms questionnaire,• gastric endoscopy with body, antrum, and fundus random biopsies,• histo-pathological analysis of samples and elaboration of bile reflux index (BRI).The same evaluation was repeated at a 6 months follow-up. RESULTS: In our series the duodeno-gastric reflux and the consensual biliary gastritis, assessed histologically with the BRI, was found in 58% of the patients after 6 months from cholecystectomy. The demonstrated bile reflux had no effect on H. pylori's gastric colonization nor on the induction of gastric precancerous lesions. CONCLUSIONS: Cholecystectomy, gold standard treatment for gallstone-related diseases, is practiced in a high percentage of patients with this condition. Such procedure, considered by many harmless, was, in our study, associated with a significant risk of developing biliary gastritis after 6 months during the postoperative period.

Diverticular disease hospital cost impact analysis: evaluation of testings and surgical procedures in inpatient and outpatient admissions.

BACKGROUND: Diverticular Disease (DD) is a common condition in Italy and in other western countries. There is not much data concerning DD's impact on budget and activity in hospitals. METHODS: The aim is to detect the clinical workload and the financial impact of diverticular disease in hospitals.Retrospective observational study of all patients treated for diverticular disease during the period of seven years in AOU Federico II. Analysis of inpatient and outpatient investigations, treatment, hospitalization and financial refunds. RESULTS: A total of 738 patients were treated and 840 hospital discharge records were registered. There were a total number of 4101 hospitalization days and 753 outpatient accesses. The investigations generated were 416 endoscopies, 197 abdominal CT scans, 177 abdominal ultrasound scans, 109 X-rays tests. A total of 193 surgical operations were performed. The total cost of this activity was € 1.656.802 or 0.2% of the total budget of the hospital. € 1.346.218, were attributable to the department of general surgery, 0.9% of the department's budget . CONCLUSIONS: The limited impact of diverticular disease on the budget and activity of AOU Federico II of Naples is mainly due to the absence of an emergency department.

Feasibility of inguinal hernioplasty under local anaesthesia in elderly patients.

BACKGROUND: The aim of this study is to evaluate the feasibility and the safety of hernioplasty under local anaesthesia in elderly patients with significant comorbidity. METHODS: A total of 218 patients underwent inguinal hernia repair with mesh between June 2009 and July 2012. Presence of comorbid conditions and complications were compared between patients younger and older than 70 years. RESULTS: Hernia repair in older patients were more likely associated with comorbid conditions than in their younger counterparts ( hypertension: 25% vs 8.16%; cardiovascular diseases: 50% vs 22%; benign prostatic hypertrophy 60% vs 30%). The most common postoperative complications in both groups were recurrence, wound infection, urinary retention. There was a slightly higher rate of complication in elderly group. CONCLUSIONS: Inguinal hernia repair with local anaesthesia is quite safe and results in a good success rate in elderly patients despite a higher rate of comorbidity typical of this kind of patient.

Peripheral blood mono-nuclear cells implantation in patients with peripheral arterial disease: a pilot study for clinical and biochemical outcome of neoangiogenesis.

BACKGROUND: Substantial progresses in the management of peripheral arterial disease (PAD) have been made in the past two decades. Progress in the understanding of the endothelial-platelet interaction during health and disease state has resulted in better antiplatelet drugs that can prevent platelet aggregation, activation and thrombosis during angioplasty and stenting. A role in physiological and pathological angiogenesis in adults has been recently shown in bone marrow-derived circulating endothelial progenitors (BM-DCEPs) identified in the peripheral blood. These findings have paved the way for the development of therapeutic neovascularization techniques using endothelial progenitors. METHODS: This pilot study includes five patients, aged 60 to 75, with a history of claudication and recruited from September 2010 to February 2011 at the A.O.U. Federico II of Naples.PBMNCs have been implanted three times in the limb with the worst ABI value in all the patients included in the study.The clinical follow up was performed during the subsequent 12 months from the beginning of the treatment. RESULTS: In four patients there was a regression of ulcerative lesions.One patient's condition improved after the first implantation but later did not respond to the further treatments.All patients achieved a pain relief as judged by the numeric pain scale. Pain relief remained satisfactory in three patients for one year. Pain gradually returned to the pre-treatment level in two patients.All patients referred an ameliorating in their quality of life expressed even by an improvement in claudication free walking distance.These improvements are reflected also by intra-arterial digital subtraction angiography (IADSA) that shows an improvement of arterial vascularization. CONCLUSIONS: The data from this study suggest an efficacy of BM-DCEPs implantation in terms of improvement of the vascularization and quality of life in patients affected by Peripheral Arterial Disease. Nevertheless a double-blind placebo-controlled study is needed to confirm our findings.