Probiotics for the management of upper respiratory diseases.

Probiotics represent an intriguing challenge in clinical practice. They are currently used worldwide in all fields of Medicine. The present Supplement reports some Italian experiences concerning a probiotic mixture (Abincol®) employed in patients with upper respiratory diseases. A group of Italian otolaryngologists conducted these experiences in a real-world setting. The results demonstrated that this compound might represent a useful therapeutic option in clinical practice. In particularly, this probiotic mixture was tested in patients with rhinosinusitis, pharyngotonsillitis, otitis media, and laryngotracheitis.

A probiotic mixture in patients with upper respiratory diseases: the point of view of the otorhinolaringologist.

Upper respiratory infections are widespread in clinical practice. Antibiotics are frequently used in the management of patients with airways infection. However, antibiotics can induce intestinal and respiratory dysbiosis that, in turn, worsens respiratory symptoms. Moreover, respiratory infections per se can cause dysbiosis. Consequently, probiotics may counterbalance the disturbed microbiota. The current clinical experience evaluated the efficacy and safety of an oral nutraceutical containing a probiotic mixture with Lactobacillus plantarum LP01 (1 billion of living cells), Lactobacillus lactis subspecies cremoris LLC02 (800 million living cells), and Lactobacillus delbrueckii subspecies delbrueckii LDD01 (200 million living cells), in 2928 outpatients with an upper respiratory infection and treated with antibiotics. Patients took one stick/daily for four weeks. Simultaneously, 2877 patients with an upper respiratory infection and treated with antibiotics were recruited as control. This probiotic mixture significantly diminished the presence and the severity of respiratory symptoms at the end of the probiotic course and, more evidently, after a 3-month follow-up. In conclusion, the current clinical experience suggested that this probiotic mixture may be considered an effective and safe therapeutic option in managing patients with an upper respiratory infection and treated with antibiotics.

Probiotics in the add-on treatment of rhinosinusitis: a clinical experience

Rhinosinusitis (RS) affects the nose and the paranasal sinus and is characterized by nasal and systemic symptoms. It may be classified as acute or chronic, based on duration. Rhinosinusitis may be clinically suspected, but the diagnosis is usually based on the endoscopy. Antibiotic therapy is frequently used for RS patients in clinical practice. However, antibiotics often induce intestinal dysbiosis associated with some clinical problems and respiratory microbiota impairment. The current clinical experience was conducted in patients with pharyngotonsillitis and treated with antibiotics. A one-month course of a probiotic mixture (Abincol® containing Lactobacillus plantarum LP01 (1 billion of living cells), Lactobacillus lactis subspecies cremoris LLC02 (800 million living cells), and Lactobacillus delbrueckii LDD01 (200 million living cells), was prescribed in the Group A, and was compared with no addon treatment, such as the Group B. Patients were evaluated at baseline (T0), at the end of antibiotic treatment (T1), at the end of probiotic course (T2), and at the end of 3-month follow-up (T3).

Probiotics in the add-on treatment of laryngotracheitis: a clinical experience.

Laryngotracheitis is a common disease, mainly characterized by dysphonia, cough, and sore throat. The diagnosis is usually based on the clinical ground, and antibiotic therapy is frequently used in clinical practice. However, antibiotics frequently induce intestinal dysbiosis associated with some clinical problems. The current clinical experience was conducted in patients with pharyngotonsillitis and treated with antibiotics. A one-month course of a probiotic mixture (Abincol® containing Lactobacillus plantarum LP01 (1 billion of living cells), Lactobacillus lactis subspecies cremoris LLC02 (800 million living cells), and Lactobacillus delbrueckii LDD01 (200 million living cells), was prescribed in the Group A, and was compared with no add-on treatment, such as the Group B. Patients were evaluated at baseline (T0), at the end of antibiotic treatment (T1), at the end of probiotic course (T2), and at the end of 3-month follow-up (T3). Globally, 833 outpatients with laryngotracheitis were enrolled: 425 in Group A and 408 in Group B. All of them were treated with a 7-10-day course of antibiotic therapy. The probiotic mixture reduced the duration of symptoms associated with antibiotic therapy already at the end of the antibiotic cycle. The intergroup comparison showed that probiotic group patients experienced less fever, tiredness, headache, pain, malaise, diarrhea, and nausea (p<0.001 for all) than control patients at T1. The probiotic course reduced the possible clinical relapse, and the use of additional medications at T2 and T3. In conclusion, the present clinical experience demonstrated that a probiotic mixture containing Lactobacillus plantarum LP01, Lactobacillus lactis subspecies cremoris LLC02, and Lactobacillus delbrueckii subspecies delbrueckii, was able to rapidly reduce symptoms associated with antibiotic therapy in patients with laryngotracheitis.

Probiotics in the add-on treatment of pharyngotonsillitis: a clinical experience.

Pharyngotonsillitis is a common disease, mainly characterized by a sore throat. It may be classified as acute or chronic, based on duration. The diagnosis is usually performed on the clinical ground, and antibiotic therapy is frequently used in clinical practice. However, antibiotics frequently induce intestinal dysbiosis associated with some clinical problems. Therefore, probiotics are commonly prescribed in patients treated with antibiotics. The current clinical experience was conducted in patients with pharyngotonsillitis and treated with antibiotics. A one-month course of a probiotic mixture (Abincol® containing Lactobacillus plantarum LP01 (1 billion of living cells), Lactobacillus lactis subspecies cremoris LLC02 (800 million of living cells), and Lactobacillus delbrueckii subspecies delbrueckii LDD01 (200 million of living cells), was prescribed in the Group A, and was compared with no add-on treatment, such as the Group B. Patients were evaluated at baseline (T0), at the end of antibiotic treatment (T1), at the end of probiotic course (T2), and at the end of 3-month follow-up (T3). Globally, 1118 outpatients were enrolled. Acute pharyngotonsillitis affected 795 subjects: 396 in Group A and 399 in Group B. Chronic pharyngotonsillitis affected 323 outpatients: 158 in Group A and 165 in Group B. All patients were usually treated with a 7-10-day course of antibiotic therapy. In patients with acute pharyngotonsillitis, the probiotic mixture significantly reduced the duration of all the symptoms (p<0.001 for all), except for the urinary tract infection, associated with antibiotic therapy which was already at the end of the antibiotic cycle (T1). The intergroup analysis showed that patients with chronic pharyngotonsillitis in Group A had significantly less tiredness, pain, and malaise (p<0.001 for all) than patients in Group B at T1. The probiotic course reduced the possible clinical relapse, and the use of additional medications at T2 and T3 in patients with both acute and chronic pharyngotonsillitis. In conclusion, the present clinical experience demonstrated that a probiotic mixture containing Lactobacillus plantarum LP01, Lactobacillus lactis subspecies cremoris LLC02, and Lactobacillus delbrueckii, was able to quickly reduce symptoms, possible relapse, and use of additional medications, associated with antibiotic therapy, in patients with both acute and chronic pharyngotonsillitis.

Probiotics in the add-on treatment of otitis media in clinical practice.

Otitis media (OM) affects the middle ear and is typically characterized by earache. OM may be classified as acute (AOM) or chronic (COM), based on symptom duration. OM may be clinically suspected, but the diagnosis is usually confirmed by the otoscopy. Antibiotic therapy is frequently used in clinical practice. However, antibiotics often induce intestinal and respiratory dysbiosis associated with some clinical problems. A one-month course of a probiotic mixture (Abincol® containing Lactobacillus plantarum LP01 (1 billion of living cells), Lactobacillus lactis subspecies cremoris LLC02 (800 million living cells), and Lactobacillus delbrueckii LDD01 (200 million living cells), was prescribed in the Group A, and was compared with no addon treatment, such as the Group B. Patients were evaluated at baseline (T0), at the end of antibiotic treatment (T1), at the end of probiotic course (T2), and at the end of 3-month follow-up (T3).

Non-pharmacological remedies for upper respiratory diseases in the pandemic COVID-19 era.

In the pandemic coronavirus disease 2019 (COVID-19) era, the need to use preventive-curative treatments is compelling. A series of non-pharmacological compounds, including supplements (oligoelements and vitamins), probiotics, and nutraceuticals, might affect the risk of COVID-19 or reducing clinical severity. Non-pharmacological remedies are easily available and usually have no relevant side effects. There is evidence that bacterial and molecular substances may potentiate the immune system against respiratory viruses. Moreover, these compounds might exert essential anti-inflammatory and antioxidant activity in COVID-19. Furthermore, nasal lavage may be an additional resource for reducing the viral load and restore the integrity of respiratory patency. Therefore, preventive courses using non-pharmacological remedies could be prescribed to reinforce the immune response and adequate treatment of upper respiratory infection with natural compounds could be considered a reasonable way to manage people in the pandemic COVID-19 era.

Broser® (bromelain, escin and selenium), oral nutraceutical, monotherapy in patients with inflammatory otorhinolaryngological disorders.

Inflammation is a common pathogenic mechanism involved in many otorhinolaryngological (ORL) disorders. Broser® is an oral nutraceutical currently containing bromelain 100 mg, escin 30 mg, and selenium 42.5 mcg. It could exert a safe and effective anti-inflammatory activity by virtue of these components. Therefore, the aim of the current survey, conducted in clinical practice of 84 Italian ORL centers, was to evaluate its safety and efficacy in the treatment of patients.

Emerging from gastroesophageal reflux (EMERGE): an Italian survey - I the viewpoint of the gastroenterologist.

Gastroesophageal reflux disease (GERD) is defined as a "disease that develops when the reflux of stomach contents induces troublesome symptoms and/or complications". From a therapeutic point of view, many options have been proposed, including proton pump inhibitors (PPI), antihistamines (H2- receptor antagonists), antacid chemical compounds, antireflux barrier (using alginates), prokinetics, inhibitors of gastric sphincters, protection of mucosal tissue, neuromodulators, nociceptor antagonists, lifestyle modification, and surgery. A new medical compound has been recently launched in Italy: Marial® (manufactured by Aurora, Milan, Italy) containing magnesium alginate and E-Gastryal®. The aim of this survey was to analyse the patients' characteristics and the prescriptive approach considering both the past or current treatments and clinical features during a visit in 56 gastroenterological centers, distributed in the whole of Italy. One thousand eight hundred forty-nine patients (46.5% males, and 53.5% females, mean age 48.59 years) were visited. Patients with positive reflux symptoms index (RSI+) had higher GIS scores than RSI- subjects. PPIs (both as monotherapy or plus add-on) were the most common medication prescribed before the visit. There was a significant change of prescription to Marial® at the visit. More precisely,, Marial® was preferentially prescribed to about a quarter of the patients, particularly to those with lower GIS score, whereas PPI plus add-on option was preferred for patients with higher GIS score. In conclusion, the current experience demonstrated that GERD may be managed considering a patient-centred work-up by using the GIS questionnaire. GIS score may be able to define the medication choice that includes also the new medical compound Marial®.

Emerging from gastroesophageal reflux (EMERGE): An Italian survey - II the viewpoint of the patient.

Gastroesophageal reflux disease (GERD) is a very common disease, as about a quarter of the Western population has GERD symptoms at least weekly and GERD is the most frequent reason for outpatient gastroenterology consultation. GERD treatment is based on proton pump inhibitor (PPI) use, but PPI may be ineffective in some patients and potentially unsafe if administered for very long time. A new medical compound (Marial®) has been introduced on the Italian market. This product contains magnesium alginate and a phytopolymer: it may be able to repair ulcer/erosion, protect mucosal tissue, and contrast acid contents. The current survey was conducted on a large group of GERD patients visited at 56 Italian gastroenterological offices. Patients were treated with PPI alone, PPI plus add-on, or Marial® for 4 weeks: the choice was decided by each gastroenterologist on the basis of the best practice criterion. A reflux symptoms index (RSI) questionnaire was used to weekly assess the clinical features. Marial® and PPI plus add-on significantly reduced RSI scores, from the second week. Noteworthy, Marial® was more effective than PPI plus add-on. In conclusion, the current survey demonstrated that patients with GERD perceived a significant improvement of GERD symptoms measured by the RSI questionnaire. Marial® was as effective as PPI plus add-on.

Gastric reflux: the therapeutical role of Marial® .

The worldwide relevance of gastroesophageal reflux disease (GERD) has had a considerable increase in recent years. The guidelines for the diagnosis and treatment of GERD are well consolidated and continuously updated. Recently, the extra-esophageal manifestations of reflux have been considered from a multidisciplinary point of view, so the symptoms of the laryngo-pharyngeal reflux (LPR) have been precisely defined. At present, a new Medical Compound (Marial®) has the indication for the treatment of both GERD and LPR. Clinical experience has initially confirmed its effectiveness in both disorders.

Correlation between the reflux finding score and the GERD impact scale in patients with gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is a very common disorder. As there is no gold standard diagnostic tool, patient-based strategy is adopted in clinical practice. In this regard, there are questionnaires able to easily and rapidly assess symptom severity directly by the patient. The GERD Impact Scale (GIS) and the Reflux Symptom Index (RSI) have been validated as diagnostic tools in routine clinical care. The present study aimed to correlate RIS values with GIS scores in a large cohort of GERD patients visited at gastroenterological clinics. Globally, 785 subjects (51.2% males, 48.8% females, mean age: 49.59 years) were visited in 56 Italian gastroenterological offices. The current study demonstrates that a GIS value >19 may be a reliable cut-off to define the positivity of the test, and GIS and RSI were significantly correlated. Therefore, both tests may be recommended for GERD patients in clinical practice.

Use of platelet rich plasma in human infertility.

Successful embryo implantation requires good quality embryo but also needs a receptive endometrium site. In our clinical practice, we daily verify that an adequate endometrial growth is reached for successful implantation. To understand whether platelet rich plasma (PRP) can improve endometrium thickness and performance, PRP treatment was carried out after at least three of the classic medical protocols currently in use had been unsuccessfully adopted. Eight patients with more than 3 cryo-transfers cancelled because of failure of endometrial growth, defined as endometrium less than 6 mm, with negative hysteroscopic screening for endometrial pathology, and with negative bacteriologic screening, before present and all previous treatment, were selected to undergo PRP treatment. In 7 out of 8 treatments, an endometrial thickness greater than 6.5 mm (mean 6.9 mm) was reached, with endometrial three-layer pattern, before progesterone administration and embryo transfer was performed. In 6 out of 7 patients, who underwent embryo transfer, beta-HCG were positive, with 2 biochemical abortions, one miscarriage at 6-week pregnancy, two babies born and one drop-out. In this study, 8 patients had extraordinarily poor endometrial quality, and the endometrium was non-responsive to conventional estrogenic therapy, resulting in cycle cancellation. After application of PRP, the endometrial thickness was satisfactory in all the patients except one. Of these, beta-HCG was positive in 6 women, the pregnancy was progressing normally in 2 women, and one had an early miscarriage. We can suppose that the multiple implantation failures were caused by inefficient expression adhesion molecules, which can hypothetically be more represented after PRP application.

Photobiomodulation in the treatment of chronic non-responding wounds.

We present a protocol of care and therapeutic approach to skin lesions, called AIMED (Anti Inflammatory Regenerative Medicine), which is based on the circularity of its phases and applied therapeutic methodologies. We used photobiomodulation (PBM) for the examination non-responding skin lesions. PBM is an adjuvant treatment for the stimulation of regenerative cellular processes, reduction of inflammation and pain and biochemical modulation of molecular response. We used PBM for the examination of skin lesions, which were not responding to other therapies. LumiHealTM protocol treatment has been applied for 3 months on 8 patients affected by infected vascular ulcers of the lower limbs resistant to previous treatments. Three patients reached positive results immediately, and the remaining 5, at the first follow-up. The use of LumiHealTM in combination with other treatments, method allowed an effective and rapid improvement of the lesions via modulation of the immune response.

Regenerative medicine in the treatment of gastro-esophageal reflux disease and laryngo-pharyngeal reflux. From research to cure.

We present our observational study on 40 patients treated with the medical device containing sodium hyaluronic acid and magnesium alginate, performing a lubricating and hydrating action. This device is in the form of a gel, with topical action to contrast gastroesophageal reflux and to exert a mechanical role of protection of the mucosal tissues (mouth-pharyngo-esophageal mucosa and gastric mucose.). Forty patients were recruited aged between 22- and 72-years-old with painful dyspeptic Gastro Esophageal Reflux Disease (GERD) symptomatology in acute or in clinical phase (25 patients) and with pharyngolaryngo- tracheal symptomatology (15 patients). Patients were divided into two clinical groups: Group A was treated with the medical device, while Group B with conventional treatments without the medical device. Subjects of both groups were also treated with proton pump inhibitors (PPIs). Follow-up was at 10, 20 and 30 days and patients were evaluated for reduction of their subjective symptoms, reduction of symptomatic and occasional therapies, reduction of inflammatory process or disappearance of epithelial lesions of the examined mucosa, healing process. The reduction of subjective symptoms was observed at 10 days in the patient with food bolus (disappearance after 5 days) and in patients with a reduction of 70%. A relevant reduction in the use of symptomatic drugs was noted. Our data are relevant considering symptom relief (heartburn, reflux and dyspepsia). New scenarios for the treatment of inflammatory diseases of the digestive and respiratory tract mucosa are at the horizon. Interdisciplinary translational research brings to the development of novel medical devices (as the one described in this study) with a high safety profile, and extremely active on the inflammation-repair-regeneration complex of different tissues and organs.

Photobiomodulation with polarized light in the treatment of cutaneous and mucosal ulcerative lesions.

In recent decades, regenerative medicine has achieved an important evolution at both a conceptual level and scientific production, which explains the current and future possibilities of therapy and daily clinical practice. The main aim of regenerative medicine is the complex system of repair/regeneration. The current literature on the subject demonstrates the advantage of visible light therapy for skin injuries and diseases with the photobiomodulation in which light at low energy levels modulates intra- and extra-cellular photoreceptors by molecular and cellular processes that can stimulate both anti-inflammatory mechanisms and cell proliferative response. The irradiation effects are activated soon after exposure. The anti-inflammatory action on some classes of cytokines and cells (e.g. mast cells and macrophages) is completed with the stimulation of the nitric oxide production, which has an anti-inflammatory and vasodilation action, and gives analgesic relief. Our attention focused on photobiomodulator medical device emitting polarized light. 30 patients (19 women and 11 men) were enrolled in the present study. They were treated for chronic lesions using Bioptron® Light Therapy System device. Patients were initially subjected to Bioptron® light for 20 min after cleansing of the lesion. The operating protocol provides 24 sessions: twice per week for 12 weeks. Twenty patients have been studied for symptoms, histological samples and ulcer characteristics. After 2 months, a reduction of 50% of the lesions was recorded in 18 patients (60%), while in the remaining patients a slower healing was observed. The total wound healing was achieved after 3 months in 13 patients (43%). The examined parameters of the symptom were exudation, pain and signs of infection. Results at 1 and 3 months were, Exudation: at 1 month reduction and positive modulation was observed in 16 patients (53%) and in 25 patients at 3 months; Pain: (evaluated with Vas scale), decreased in 21 patients at 1 month (70%) and in 100% of cases at 3 months; Infections: regressed or disappeared in 100% of cases after the first month. Today, it is no longer time for monotherapy applications, especially in regenerative medicine and the adoption of biophysical therapies can play a positive anti-inflammatory and regenerative role enhancing the function of non-invasive therapies.

Chronic inflammation therapy combined with low dose cytokines in the treatment of chronic ulcers of lower limbs.

Prevalence of chronic venous leg ulcers has increased from 55% to 75% in 10 years. We treat chronic vascular lesions according to a cyclic multiphase method that follows the instrumental and differential etiologic diagnosis of ulcers of the lower limbs. The AIMED (Anti Inflammatory Regenerative Medicine) operating model follows the diagnostic phase and is structured in 5 interconnected phases. Mare evaluation, pH control, biofilm removal and prevention and infections are approached according to the International Guidelines. Low-dose cytokine therapy to contrast the inflammatory process are administrated to the patients. Chronic skin lesions of these patients, treated according to the AIMED protocol, have been evaluated twice a week. The clinical evaluation parameters evaluated by us were: reduction of pain at 15 and 30 days, reduction of 50% of the injury at 30 days, characteristics of perilesional skin (edema, erythema) and global profile of the patient. The so-called Low Dose Cytokines therapy is changing the previous therapeutic algorithms thanks to a safe and effective systemic cytokines-receptors interactive physiological process.