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Background: High concentration protein formulation (HCPF) development needs to balance protein stability attributes such as conformational/colloidal stability, chemical stability, and solution properties such as viscosity and osmolality., Methodology: A three-phase design is established in this work. In Phase 1, conformational and colloidal stability are measured by 384-well-based high-throughput (HT) biophysical screening while viscosity reduction screening is performed with HT viscosity screening. Collectively, the biophysical and viscosity screening data are leveraged to design the phase 2 of short-term stability study, executed using 96-well plates under thermal and freeze/thaw stresses. In phase 2, samples are analyzed by stability-indicating assays and processed with pair-wise Student's t-test analyses to choose the final formulations. In phase 3, the final formulations are then confirmed through a one-month accelerated stability in glass vials., Results: Using a model antibody A (mAb-A), the initial HT screening successfully established the 384-well based platform. A lead formulation was chosen from the second round based on statistical analyses and subsequently tested against the commercial formulation of mAb-A as a control. Compared to the control, the lead formulation reduced the viscosity of mAb-A by 30% and decreased subvisible particles after thermal stress by 80%., Conclusions: HT biophysical screening in 384-well plates was demonstrated to effectively guide the rational design of a high-throughput stability screening study using 96-well plates. This platform enables the identification of a high concentration formulation within seven weeks within the first two phases of study that strategically balance stability with solution properties, thus achieving a rapid development of HCPF., Competing Interests: Declarations. Conflict of Interest: LX, MP, RM, MB, ZZ, CL, KR, SR, and YL are or were employees and/or shareholders of WuXi Biologics. Ethics and Consent Statement: Not applicable. Animal Research Statement: Not applicable., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To show the effectiveness of goal-oriented proprioceptive training in subacute stroke for balance, autonomy, and fall risk., Methods: Out a total of 35 patients, consistent in age (75.31±8.65 years), type of stroke (ischemic, 3 to 11 weeks before), and motor impairment, 18 patients underwent solely proprioceptive rehabilitation, the other 17 dual task exercises. The study assessed autonomy using Barthel Index, fall risk with Timed Up and Go Test (TUG), balance through Berg Balance Scale (BBS) and Tinetti test., Results: After two months, significant improvements were recorded in Barthel Index, BBS (p<0.0001), Tinetti test (p<0.0001 in dual task group, p=0.0029 in single task group), and TUG (p=0.0052 in dual task group, p=0.0020 in single task group) in both groups. Comparing the two groups, dual task group showed a significant difference in Tinetti balance assessment (p=0.0052), between the total score of Tinetti test and TUG in single (p=0.0271), and dual task (p=0.0235). Likewise, Tinetti gait test was significantly related to TUG in single (p=0.0536), and dual task (p=0.0466), while Tinetti balance test to Barthel Index (p=0.0394), BBS (p<0.0001), and TUG in single (p=0.0219), and dual task (p=0.0196). Lastly, there is a positive correlation of the use of aids with BBS (p=0.0074), and total score of Tinetti test (p=0.0160)., Conclusion: In subacute stroke, goal-oriented proprioceptive training improved balance, but only partially autonomy. Furthermore, the use of aids after dual-task exercises improved recovery of balance, but did not reduced falls.

Background: Chemotherapy, as well as opioid and antiemetic drugs, can contribute to constipation in oncological patients. This systematic review aims to analyse the potential of specific rehabilitation strategies and alternative strategies for improving constipation symptoms, with the goal of incorporating these strategies into a dedicated protocol for managing cancer-related constipation. This could potentially reduce the dosages of or eliminate the need for constipation medications., Methods: A systematic search was conducted on PubMed, Scopus and Web of Science. The review included studies analysing constipation complaints in cancer patients treated with rehabilitation, acupuncture and osteopathy., Results: The review included 16 studies in line with PRISMA and PICOS criteria. Most studies showed that physical exercise, abdominal massage, TENS, acupuncture and education on the correct defecation position positively impacted the management of constipation and quality of life in oncological patients. A physiotherapy program involving massages as well as aerobic and resistance training improved constipation in oncological women, regardless of age, sex and frailty. A combination of abdominal massage, abdominal muscle stretching and education on proper defecation position alleviated the severity of constipation and related depression. However, the outcomes regarding TENS were yet inconsistent. Another technique, becoming increasingly common for constipation, and demonstrating positive results, involved stimulating trigger points through acupressure and acupuncture. Conversely, osteopathic and superficial manipulations more frequently required constipation medications than did the other alternative approaches. However, no existing studies have proposed a specific protocol to manage cancer-related constipation., Conclusions: The results of the studies confirm the positive influences of rehabilitation, osteopathy and acupuncture on constipation and pain in oncological patients. Nevertheless, further studies are required to establish the best type, timing and duration of treatment, as well as how the stage and location of the cancer and the cause of constipation (drug-induced or functional) impact the results.

This systematic review aims to reveal the effectiveness of proprioceptive exercise combined with dual-task training in stroke patients. The research was conducted using PubMed, Cochrane Library, Web of Science, and Scopus databases to evaluate studies of rehabilitation interventions with proprioceptive and dual-task exercises in patients with stroke. The keywords for the search were: "stroke" AND "proprioception" OR "proprioceptive" AND "rehabilitation" OR "training" OR "exercises" AND "dual-task" OR "task-performance" with the following inclusion criteria: comparative studies of rehabilitation interventions with proprioceptive and dual-task exercises in stroke patients. Of the 104,014 studies identified, 23 were included according to the inclusion criteria. Proprioceptive and dual-task exercises stimulate and promote postural balance, gait, and quality of life and reduce the risk of falls in stroke patients compared with traditional rehabilitation programs. In conclusion, this systematic review suggests that proprioceptive exercise combined with dual-task training is needed to improve balance and recover gait. Moreover, it provides a comprehensive overview of the literature on the various proprioceptive treatments with contextual dual-task exercises for imbalance after stroke, providing a guide for choosing a complete rehabilitation protocol that combines these two techniques.

Background: Pneumomediastinum (PNM) can develop as a severe complication of severe COVID-19 and may be correlated with greater morbidity and mortality. PNM is a rarely reported complication in COVID-19 patients and usually associated with endotracheal intubation., Methods: Our aim was to describe the characteristics of patients with PNM in twenty-one patients with COVID-19 related pneumonia and acute respiratory failure in a retrospective case series., Results: Twenty-one patients were diagnosed, four were treated with high-flow nasal cannula, thirteen with non invasive ventilation and four with invasive mechanical ventilation. In five cases PNM was massive and associated to subcutaneous emphysema; more rarely PNM was associated with pneumothorax. Conservative management was the most used therapeutic strategy., Conclusions: PNM is a serious and not extremely rare complication of severe forms of pulmonary involvement of COVID-19. The clinician should consider this rare complication; moreover, we suggest being careful when clinicians start mechanical ventilation.

Background: COVID-19 has high mortality rate mainly stemming from acute respiratory distress leading to respiratory failure (ARF). Aim of the study was to evaluate the management of severe ARF due to COVID-19 pneumonia using noninvasive ventilatory support (NIVS), studying safety and effectiveness of NIVS., Methods: This is a retrospective, multicenter study. Primary outcomes were NIVS failure with intubation rate and hospital mortality. Secondary outcomes were hospital stay and factors related to NIVS failure and mortality. These outcomes were compared with patients intubated and admitted to ICU., Results: One hundred sixty-two patients were hospitalized because of severe respiratory failure (PaO2/FiO2 ratio <250). One hundred thirty-eight patients were admitted to Respiratory Intermediate Care Unit (RICU) for a NIVS trial. One hundred patients were treated successfully with NIVS (74.5%); 38 failed NIVS trial (27.5%). In-hospital mortality was 23.18% in RICU group and 30.55% in ICU group. Patients with NIVS failure were older, had a lower number of lymphocytes, a higher IL-6, lower PaO2, PaC O2, PaO2/FiO2 ratio, higher respiratory rate (RR) and heart rate at admission and lower PaO2, and PaO2/FiO2 ratio and higher RR after 1-6 hours. Multivariate analysis identified higher age, C-reactive protein as well as RR after 1-6 hours and PaO2/FiO2 ratio after 1-6 hours as an independent predictor mortality., Conclusions: NIVS is a safe and effective strategy in the treatment of severe ARF due to COVID-19 related pneumonia, that reduces mortality and length of hospital stay in the carefully selected patients.

Objective: A systematic review and a meta-analysis were performed to identify the main characteristics of voice disturbances in bulbar amyotrophic lateral sclerosis. Materials and Methods: Literature searches with the keywords: "amyotrophic lateral sclerosis" and "dysarthria" and "intelligibility" were conducted in PubMed, EMBASE, Cochrane Library and Web of Science to perform the systematic review about the articulatory disorders and with the keyword "amyotrophic lateral sclerosis" and "voice" to conduct the meta-analysis about the phonetic changes in patients with bulbar ALS. Results: Seven publications met the inclusion criteria and were included in the meta-analysis, twenty-six publications were included in the systematic review. The data within the meta-analysis revealed that several voice parameters including Jitter, Shimmer, Noise to Harmonic Ratio discriminated best between bulbar amyotrophic lateral sclerosis and healthy controls. On the other hand, significant variations of fundamental frequency were not observed. Conclusion: Acoustic analysis of voice and articulatory analysis contributes to identification of the earliest signs of bulbar degeneration and allows the identification of changes in voice parameters for an early detection, for predicting bulbar involvement and the worsening of disease, for targeting specific intervention. Among the voice parameters, Jitter and Shimmer discriminated better bulbar involvement, they are significantly increased in the patients, on the contrary maximum phonation time is significantly worsened. The careful monitoring of speech symptoms improves diagnostic accuracy and the close cooperation of a multidisciplinary team (physicians as otolaryngologist and physiatrist, speech and language therapists, physiotherapist, dietitians, caregivers, the patients, and their relatives) could be essential.

Aim: To systematically review all the literature, focusing on instrumental quantitative assessment of voice in patients with Parkinson's disease (PD). Furthermore, a meta-analysis was performed to identify the main characteristics of voice disturbances in PD., Patients and Methods: Literature searches with the keywords «Parkinson» and «voice» were conducted in PubMed, EMBASE, Cochrane Library and Web of Science. Main inclusion criteria were: clinically confirmed PD and instrumented measurement of voice parameters with acoustic analysis of voice., Results: Fourteen publications met the inclusion criteria and were included in the meta-analysis. The data within the meta-analysis revealed that several voice parameters including jitter, shimmer and fundamental frequency variation presented significant variations between patients with EP and healthy controls. Significant variations of fundamental frequency, maximum phonation time, harmonic to noise ratio, standard deviation of fundamental frequency were observed, but with a high heterogeneity between the studies. On the other hand, significant variations of noise to harmonic ratio, s/z ratio, variation of amplitude were not observed., Conclusion: Acoustic analysis of voice, using an electronic system, allows the identification of changes in voice parameters for predicting the worsening of disease and for targeting specific intervention. Among the voice parameters, jitter and shimmer significantly increased in patients with PD.

Objective: We investigated the associations between adhesive capsulitis (AC) and a specific psychological profile., Methods: We assessed 72 patients with phase-II AC. In our study, 36 patients were affected by primary disease and 36 by secondary disease. The inclusion criteria were as follows: unilateral AC and pain in the shoulder for at least two months. The exclusion criteria were: psychiatric and neurological manifestations with a previous diagnosis and inability to comprehend the instruments. Outcomes were determined at 52 weeks. Shoulder pain severity was assessed with the Visual Analog Scale. We also measured the range of motion with a universal goniometer and the strength with the Medical Research Council. We assessed the personality traits of our patients with the Cloninger's Temperament and Character Inventory and the Multidimensional Perfectionism Scale., Results: Patients with primary AC needed more time to improve the symptomatology compared to the group with the secondary disease (p<0.01). Patients with primary AC complained of severe and lasting pain more frequently than patients with the secondary disease (p< 0.01). In patients with primary disease, the prevalence of perfectionism, low levels of novelty seeking, and high levels of harm avoidance were 88.2 and 86.2%, and 80.4, respectively, and below 20 percent in patients with secondary AC disease., Conclusion: We found a significant correlation between primary AC and particular personality traits, indicating an interaction between psychological and somatic factors.

Background and Purpose: Pharmacy schools must have a framework to ensure students have the necessary knowledge, skills, attitudes, and behaviors to be successful during advanced pharmacy practice experiences (APPEs)., Educational Activity and Setting: Ten summative assessments, called APPE-readiness assessments (ARAs), were developed based on eight competencies encompassing skills, behaviors, and attitudes that must be demonstrated prior to APPEs. All eight competencies were assessed in the course Case Studies in Pharmacotherapy IV, which is offered in the final semester of the didactic curriculum immediately prior to APPEs. A 15-question pre- and post-survey was conducted to assess student confidence in performing each APPE-readiness competency. Cohort data was evaluated by the curriculum and assessment committee to assess curriculum effectiveness and areas for improvement., Findings: Upon completion of the course, the average first-attempt pass rate across all ARAs was 92.4%. All students who failed on the first attempt passed on the second attempt, thereby demonstrating APPE-readiness. Out of 62 students, 45 and 44 completed the pre- and post-survey, respectively. Prior to the ARAs, the overall average of students who felt (strongly) confident about their ability to perform each competency was 82.2 ± 2.1%. This increased to 92.6 ± 1.6% after the ARAs., Summary: The development of an APPE-readiness assessment plan focusing on skills, attitudes, and behaviors provides insight into student and cohort performance and allows for continuous quality assurance of the pre-APPE curriculum., Competing Interests: Declaration of competing interest None., (Copyright © 2019. Published by Elsevier Inc.)

Objective: We reported our multidisciplinary protocol for the management of fibromyalgia associated with imbalance. Our aim was to verify the effectiveness of a proprioceptive training program as a complementary therapy for a traditional protocol of education, mindfulness, and exercise training for the management of fibromyalgia associated with imbalance., Methods: Retrospective cohort study on 84 women, with primary fibromyalgia associated to imbalance. A group of patients performed traditional exercise training; in a second group the training was supplemented with proprioception exercises. Each session lasted from 40 to 60 minutes and was performed three times a week for 12 weeks., Results: After three months of training and eight months after the end of the training, the balance evaluation revealed significant differences in the comparison of the Timed Up and Go test, Berg Balance Scale, and Tinetti scale with the baseline, there was a better improvement in the proprioceptive training group (p<0.05). A reduction in pain and improvement in functional and muscular performance and quality of life were observed in both groups (p<0.05), but with no significant differences between them in the Numeric Pain Rating Scale, Fibromyalgia Impact Questionnaire, and Short Form Health Survey (p>0.05). Fifteen months after the end of the program, the effects of training were not maintained., Conclusion: The present study revealed that training supplemented with proprioception exercises has beneficial effects on clinical findings and improves balance in patients with fibromyalgia, even if the positive results did not persist after the interruption of the rehabilitative program in the long term.

Objective: With high-resolution real-time ultrasonography we investigated the muscle architectural parameters of vastus lateralis in healthy volunteers., Purposes: We determined the reproducibility and validity of ultrasonography and the role of the ultrasonographer in assessing muscle architecture. We proposed the most appropriate clinical parameters for objective measurements and an ultrasound protocol of muscle architecture., Methods: We conducted an intraobserver and interobserver study. We investigated 21 healthy male volunteers. The subjects were independently evaluated by four different operators using high-resolution real-time ultrasonography. To assess the reproducibility of ultrasound examinations, four operators repeated measurements using the same ultrasound device. Muscle thickness, muscle volume, muscle fiber pennation angle, and subcutaneous adiposity of the vastus lateralis muscle were measured., Results: Intra-observer (ICC 0.92-0.97), interobserver (ICC 0.78-0.92) reproducibility was good to excellent for all measurements., Conclusion: Simple, reproducible, non-invasive ultrasound measurements of muscle structure easily demonstrated differences in muscle morphology. With a protocol and with objective and repeatable measurements, sonographers from different backgrounds could obtain an objective measurement of ultrasound images with little differences and low variability in results, thanks to the upgrading of diagnostic ultrasound imaging and their clinical skills.

Introduction and Objectives: The objective of this study was to examine the role of different specialists in the diagnosis of amyotrophic lateral sclerosis (ALS), to understand changes in verbal expression and phonation, respiratory dynamics and swallowing that occurred rapidly over a short period of time., Materials and Methods: 22 patients with bulbar ALS were submitted for voice assessment, ENT evaluation, Multi-Dimensional Voice Program (MDVP), spectrogram, electroglottography, fiberoptic endoscopic evaluation of swallowing., Results: In the early stage of the disease, the oral tract and velopharyngeal port were involved. Three months after the initial symptoms, most of the patients presented hoarseness, breathy voice, dysarthria, pitch modulation problems and difficulties in pronunciation of explosive, velar and lingual consonants. Values of MDVP were altered. Spectrogram showed an additional formant, due to nasal resonance. Electroglottography showed periodic oscillation of the vocal folds only during short vocal cycle. Swallowing was characterized by weakness and incoordination of oro-pharyngeal muscles with penetration or aspiration., Conclusions: A specific multidisciplinary clinical protocol was designed to report vocal parameters and swallowing disorders that changed more quickly in bulbar ALS patients. Furthermore, the patients were stratified according to involvement of pharyngeal structures, and severity index., (Copyright © 2018 Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. Publicado por Elsevier España, S.L.U. All rights reserved.)

Since 1798, the men and women of the Commissioned Corps of the US Public Health Service (USPHS), one of the seven US uniformed services, have served on the front lines of public health. Two hundred years after the start of the USPHS, the first physician assistant (PA) entered the service to carry on the tradition of protecting, promoting, and advancing the health and safety of the nation. These dedicated clinicians are involved in healthcare delivery to underserved and vulnerable populations, disease control and prevention, biomedical research, food and drug regulation, and national and international response efforts for natural and man-made disasters. This article describes how PAs in the Commissioned Corps of the USPHS have impacted the health and safety of not only the United States but also the international community.

The GISTs are rare tumours but even rarer is the localization in some districts. We reported two GISTs of the duodenum, two of the omentum and peritoneum, one of the rectum and one of a Meckel's diverticulum. These exceptional locations are confirmed by the relative difficult diagnosis, obtained in some cases only by the surgical treatment despite the CT and MR. The endoscopy is useful in hemorrhagic and duodenum forms, only for the diagnosis and for the control of blood loss. Surgical treatment in all cases was decisive without the need to make use of adjuvant therapy, with positive long-term results, which excluded the disappearance of relapses or secondary lesions.

Objective: The objective was to analyze the association of radiotherapy with gastroesophageal reflux as determinant of fistula related pathology, in voice prosthesis patients., Study Design: Retrospective study., Methods: Sixty-one laryngectomy patients were enrolled between 2005 and 2012. All patients underwent phonatory rehabilitation with voice prosthesis, along with evidence of gastroesophageal reflux disease, for which proton pump inhibitors (PPIs) were prescribed. We analyzed the occurrence of fistula-related problems among patients who received postoperative radiotherapy and those patients who did not., Results: We observed a higher rate of failure of speech rehabilitation in laryngectomy patients with gastroesphageal reflux: this occurred when they had a history of postoperative radiotherapy (45%) compared with patients who did not (17%) (P < 0.05), although all patients were treated with PPIs., Conclusion: Our results seem to confirm the importance of postoperative radiotherapy with gastroesophageal reflux for the determinism of fistula-related problems., (Copyright © 2014 The Voice Foundation. Published by Mosby, Inc. All rights reserved.)

Moschcowitz's syndrome or thrombotic thrombocytopenic purpura is a quite rare pathology in childhood, being, as a matter of fact, more frequent among adult people. Often it is hard to distinguish from other pathologies in children both for its rare incidence and for the presence of clinical forms that are very heterogeneous and difficult to be classified. We report on a 13 year-old girl suffering from Moschcowitz's syndrome, in whom respiratory failure and pharyngeal hematoma were the first sign of the disease follone by jaundice, hematoma of the arm and limbs. The girl was treated with plasmapheresis with an improvement of her general condition. Since then we have followed up the girl for two years without any reappearance of the symptomatology. To our knowledge this is the first report of this peculiar presentation in children.

The aim of our work has been to evaluate the different options of tracheoesophageal voice rehabilitation in over 70-year-old patients, who had undergone laryngectomy, assessing advantages and drawbacks of this method of vocal recovery. A retrospective study has been carried out. This has included 40 subjects, all aged more than 70 years old, who have been referred to tracheoesophageal voice rehabilitation. It has been realized a phonatory fistula between trachea and esophagus with prosthesis positioning by means of a primary puncture in 18 cases and it has been realized a secondary puncture in 22 cases. The results gathered in these patients were compared with data obtained from a group made of 39 patients, less than 70 years of age that therefore represented our control group. In primary tracheoesophageal puncture (TEP), the short-term success was 67 %, while in the 22 cases who underwent secondary TEP, the short-term success was 64 %. After 2 years from TEP, the long-term success was 82.5 %. In the control group, the short-term success was 65 % in primary TEP and 73 % in secondary TEP. After 2 years from TEP, the long-term success was 77 %. The evaluation of the results has shown the absence of a statistically significant difference both as regards complications incidence, during and after surgery (p > 0.9) and as regards overall success ratio of prosthesis implants between the two groups (p > 0.7). The possibilities of tracheoesophageal recovery of elderly patients do not show dissimilarities in comparison with the results in younger subjects.

Hemifacial spasm (HFS) is a facial movement disorder characterized by involuntary, unilateral and intermittent contractions of the facial muscles. It is one of the syndromes related to neurovascular conflict, first described by Jannetta et al. in 1979. Typically, HFS is due to pulsatile compression by the anterior inferior cerebellar artery. We describe a rare case of left developmental venous anomaly in a 59-year-old man referred to us with a six-month history of left-sided HFS. We performed an MR study of the brain and cerebellopontine angles, which demonstrated a compression of the ipsilateral facial nerve by the developmental venous anomaly.

Blunt head trauma without any temporal bone fracture or longitudinal temporal bone fracture, with an associated fracture of the labyrinth may cause labyrinthine injury with sensor neural hearing loss and vertigo because of a concussive injury to the membranous labyrinth. Sudden sensory neural hearing loss is relatively frequent. In most cases, the etiology is not discovered. One of the possible causes for sudden deafness is inner labyrinth bleeding or concussion, which were difficult to diagnose before the advent of magnetic resonance imaging. Vertigo without a demonstrable fracture may also be the result of labyrinthine concussion, cupololithiasis and perilymphatic fistula. We describe the clinical case of a patient with acute traumatic hearing loss and vertigo, without skull base fracture detected on computed tomography. Magnetic resonance study was also performed. We have integrated the discussion with features that allow the differential diagnosis from other similar conditions.

Osteoblastoma is a solitary, benign bone tumor that is rarely localized in the frontal sinus. It consists of hypocellular mineralized tissue that may form large masses or irregular trabeculae. A 31 year old man came to our attention with a 7 month history of diplopia, photophobia, frontal headhaches and progressive exophthalmos with proptosis of the left eye. The patient was submitted to computed tomography (CT) which allowed to appraise the extension of the lesion. The mass expanded inside the left frontal sinus and the upper ethmoidal cells invading the left orbital roof. Considering the extension of the tumor, the site and the connections with contiguous structures, a combination of endoscopic endonasal technique with intraorbital approach was performed. At histological examination typical features of benign osteoblastoma were observed. The sites of predilection for the tumor are the long bones, vertebral column, and small bones of hands and feet. Its occurrence in the skull and jaw bones is relatively rare and represents only 15% of all osteoblastomas. To our knowledge, only 5 cases of osteoblastoma of the frontal sinus have been previously reported in the English-language literature. This report describes a case of benign osteoblastoma in a rare site, namely, the frontal sinus with particular attention about the differential diagnosis and the treatment.

Introduction: A review of the available literature has shown that the indications, epidemiology, and complications for tracheostomies are changing, and that no definite guidelines have been established. In the 1970s, the most common indication for tracheostomies in children was acute inflammatory airway obstruction. Modern neonatal intensive care units (ICU) have turned long-term intubation into an alternative to a tracheostomy. Currently, long-term intubation has become the most important indication for tracheostomies in children., Patients and Methods: We present our series involving tracheostomies performed in paediatric patients between 2004 and 2008 at our hospital. Sixteen patients underwent tracheostomies for respiratory failure and upper airway obstruction., Results: The total complications rate was 37.5%. In children < 1 year of age, the complications rate was 25%, while in children > 1 year of age, the complications rate was 12.5%., Conclusions: Long-term intubation and its sequelae have now become one of the most important indications for tracheostomies in the paediatric age group.

The objective of this study is to evaluate the incidence of pathologic gastroesophageal reflux in laryngectomized patient with phonatory prosthesis, analyzing potential related problems and appraising, at the same time, the effectiveness of a therapeutic protocol. A retrospective study was conducted on 43 phonatory prosthesis patients who had problems with regard to recurrent tracheoesophageal granulations, the need of frequent prosthesis replacement, within a 3-month period, and unsatisfactory vocal results. Such patients underwent physical examination of the fistula region and of the neopharynx and were submitted to esophagogastroduodenoscopy. Moreover the group of patients underwent a therapeutic protocol and were re-evaluated posttreatment, examining fistula region both on the tracheal side and on the esophageal side through videolaryngostroboscopy. Of the 43 recruited patients 13 (30%) presented tracheoesophageal granulations, 20 (46.5%) unsatisfactory vocal results and 10 (23.5%) frequent prosthesis replacement, within a 3-month period, due to abnormal biofilm development. In particular, of the 13 patients who had recurrent granulations, the evaluation results revealed the presence of gastroesophageal reflux disease (GERD) in 6 cases (46%). In the group of patients presenting unsatisfactory vocal results GERD was shown in 13 cases (65%). In the third group of patients GERD was found in two cases (20%). The overall analysis of the data gathered, allowed to identify GERD in 21 (49%) of the 43 patients submitted to the study. The results posttreatment indicated, in the first group, the disappearance or a significant (>75%) volume reduction of such formation in five cases (38%, p = 0.002). In the second group an overall improvement in the quality of voice was displayed at least for 12 patients (60%, p = 0.0001). Finally in the last group an increase of the prosthesis life was recorded in four (40%, p = 0.05) of the ten patients who had the need of prosthesis replacement within 3 months. Also the 22 GERD negative cases (51%) underwent the treatment, therefore representing the control group, whose posttreatment results showed substantial modifications in just two cases (9%). The data obtained suggest a high degree of correlation between the presence of pathologic gastric reflux and the partial or total prosthesis failure. The introduction of a specific therapeutic protocol has allowed to improve the quality of prosthesis (QoP) in 22 of the 43 patients (p < 0.001) who had a pathologic condition of the fistula and of the prosthesis.

Objective: To describe the characteristics of patients with influenza A (H1N1)-associated pneumonia treated at two hospitals in the region of Liguria, Italy, as well as to describe their treatment and outcomes., Methods: This was a prospective observational study including all patients older than 16 years of age with a confirmed diagnosis of influenza A (H1N1) who were admitted to Villa Scassi Hospital, in the city of Genoa, Italy, or to the Sestri Levante General Hospital, in the city of Sestri Levante, Italy, between September of 2009 and January of 2010. The primary outcome measure was mortality within 60 days after diagnosis. Secondary outcome measures were the need for mechanical ventilation and the length of hospital stay., Results: Of the 40 patients with a confirmed diagnosis of influenza A (H1N1), 27 presented pneumonia during the study period. The mean age of the 27 patients was 42.8 ± 14.8 years, and the mean length of hospital stay was 11.6 ± 8.2 days. Of the 27 patients, 20 had respiratory failure, 4 underwent invasive mechanical ventilation, and 5 underwent noninvasive ventilation. One patient had comorbidities, developed multiple organ failure, and died., Conclusions: During the influenza A (H1N1) pandemic, the associated mortality rate was lower in Italy than in other countries, and cases reported in the country typically had a milder course than did those reported elsewhere. Nevertheless, 9 of our cases (33%) rapidly evolved to respiratory failure, requiring mechanical ventilation.

Aim: Fungal infections have become one of the emerging complications in intensive care patients and the morbidity and mortality linked to these infections underlines the importance of managing these pathologies., Methods: The clinical and laboratory difficulties of diagnosing candidiasis prompted us to identify patients at risk and to intervene as soon as possible, where there was the "suspicion" of active infection, using adequate, so-called "empiric" treatment. The major risk factors include the use of invasive devices (central venous catheters), the administration of multiple antibiotic treatment and parenteral nutrition. In our Intensive Care ward (multi-purpose), we examined 1933 patients who had undergoing 1211 urine cultures (following consolidated clinical criteria). "Empiric treatment" was used in 378 high-risk patients with unstable clinical symptoms and positive urinary fungal colonisations using high-dose fluconazole (800 mg/die) according to the guidelines set down by BSAC. The mean duration of treatment was 12+2 days and urine cultures became negative in all patients after 1 or 2 weeks of treatment., Results: We observed that fluconazole was generally well tolerated: only 10% of patients presented augmented hepatic transaminase. This phenomenon was always transient. Renal function remained unchanged (creatinine clearance). A severe infection with hematogenous dissemination was reported in 6 cases: "empiric treatment" was used in 5 cases with 800 mg/die of fluconazole and 1 case received amphotericin B 1 mg/kg/die (because no clinical improvement was observed after 48-72 hours of fluconazole treatment). Three of these 6 cases died, 2 of which were not directly linked to fungal infection, and 3 patient were discharged from the ward., Conclusions: We found that fluconazole offers a treatment option that is less toxic, less expensive and equally effective for these infections, provided that it is used at an adequate dose and that high-risk patients are identified for "empiric treatment". No significant increases in resistance were noted, as is demonstrated by the fact that only 1 case of candidemia required conversion to amphotericin B.

Acute cholecystitis is one of the most frequent causes of admissions to surgical departments. The development of liver abscesses is an uncommon and underrated complication of acute cholecystitis. In this study we report on our experience with the treatment of 5 cases of liver abscesses secondary to acute cholecystitis. All 5 cases were characterised by a lengthy period between the onset of acute cholecystitis symptoms and the subsequent diagnosis of a secondary liver abscess. In 4 out of 5 patients, admission for liver abscess occurred 12, 30, 50 and 120 days, respectively, after the acute cholecystitis episode. The liver abscesses were successfully treated with percutaneous drainage under US guidance (4 cases) and 4 patients underwent percutaneous cholecystostomy to treat the acute cholecystitis. After resolution of the acute phase, an elective cholecystectomy was performed in 4 out of 5 cases. Failure to diagnose acute cholecystitis at onset or inappropriate treatment of the condition could lead to the development of liver abscesses.

Background: The incidence of paraaortic lymph node metastasis (N4) in relation with the site of the tumour, and survival in patients with gastric cancer who underwent gastric resection and superextended lymphadenectomy (D4), have been analyzed., Methods: The frequency of paraaortic lymph node metastasis was studied in 132 patients who underwent gastrectomy with D4 lymphadenectomy during the period June 1988 - December 2000. Six patients with plastic linitis and 3 with carcinoma of the gastric stump were excluded from the analysis., Results: In personal experience the most frequent postoperative morbidity were respiratory complication (7.6%) and pancreatic fistula (6.8%). Among the 132 patients the total number of dissected nodes was 6362 and the mean number of dissected nodes per case was 48.2. The total number of retrieved lymph nodes from the paraaortic station was 755 with a mean number 5.7 per patients. N4 nodal involvement was found in 25 (19%) of 132 patients: 14 (36%) patients with carcinoma located in the proximal third, 5 (13%) with tumour located in the middle third and 6 (11%) with carcinoma of the distal third of the stomach. The median survival time and the overall cumulative 5-year survival rate for curatively (R0) resected patients were 74 months and 52% respectively., Conclusions: The presence of metastasis in paraaortic lymph nodes in 19% of our patients, the low morbidity and mortality, the good survival after superextended lymphadenectomy, suggest that this lymphadenectomy should be considered in the curative surgical treatment of advanced gastric cancer, especially if located in the proximal third of the stomach (N4 in 36% of cases).

Background: To assess an additional prognostic value of Goseki histological classification to TNM staging system in adenocarcinoma of the cardia., Methods: Sixty-one patients curatively resected for advanced (T2, T3 and T4) cardia cancer at the I Division of General Surgery, University of Verona were classified in four different grades according to Goseki. Survival curves were estimated with Kaplan-Meier method and compared by the log-rank test. Multivariate analysis was performed by Cox regression model. c2 test was used to compare Goseki to Lauren classification and grading. After discharge from hospital all patients were followed with a mean follow-up of 39.5 months., Results: Lauren classification and grading were significantly related to tubular differentiation (p<0.01). Kaplan-Meier estimates of survival showed a better 5-year outcome for tumors with good tubular differentiation (19%), even though the difference with poor tubular differentiated tumors was not statistically significant (p'0.06). Diffuse type carcinomas and tumors with poor cytological differentiation showed a worse prognosis at univariate analysis (p<0.01). Multivariate analysis showed no additional prognostic significance of any of the histological classification analyzed. Only T (p<0.02; RR 2.2; IC 1.2-4) and N (p<0.01; RR 5; IC 2.4-11) were independent prognostic factors., Conclusions: In adenocarcinoma of the cardia, Goseki classification did not add any information to Lauren classification and to TNM staging system.

The microscopic detection of free peritoneal tumour cells in peritoneal lavage fluid in gastric cancer patients is a useful predictor of peritoneal recurrence and poor prognosis. The aim of this study was to verify the prognostic significance of intraoperative peritoneal lavage cytology and its value as a predictor of peritoneal recurrence. We evaluated the presence of free peritoneal tumour cells with extemporary cytological examination in a series of 170 peritoneal washing samples from patients undergoing gastrectomy for gastric cancer over the period from January 1992 to June 2001. Twenty-eight patients (16%) had positive extemporary lavage cytology and there were no false-negatives as compared with the final examination. All patients with positive cytology presented serosal infiltration (T3/T4). Positive peritoneal lavage cytology was a predictor of poor prognosis and peritoneal recurrence: the 24 month survival rate was 17% for positive and 60% for negative cases (P = 0.003); in positive cases 71% of recurrences were located in the peritoneum. Intraoperative cytological examination of peritoneal washings can detect the presence of free malignant cells in the peritoneal cavity and can be used to select patients who may benefit from intraperitoneal chemotherapy.

Objective: To find out the extent of involvement of the para-aortic nodes in patients with adenocarcinoma of the gastric cardia., Design: Open prospective study., Setting: Teaching hospital, Italy., Subjects: 23 patients with advanced adenocarcinoma of the cardia (type II, n = 10, and type III, n = 13) who were treated by total gastrectomy with resection of the distal oesophagus and extended lymphadenectomy (D4) between January 1997 and June 1999. These were compared with 21 patients with advanced carcinoma of the proximal third of the stomach who had total gastrectomy with D4 lymphadenectomy during the same period. Lymph nodes were retrieved immediately postoperatively and assigned to the appropriate station according to the classification of the Japanese Research Society for Gastric Cancer., Main Outcome Measures: Number of para-aortic and other nodes involved., Results: 22 of the 23 patients had lymph node metastases, and in 5 the para-aortic nodes were involved (N4). N3 lymph nodes were involved in only 1 patient, despite involvement of para-aortic nodes. Among the 5 patients with N4 metastases, 1 had only N1 metastases in addition, with no involvement of N2 or N3 nodes. Patients with involved N4 nodes had more nodes involved overall than those who did not (mean (SD) 17 (5) compared with 8 (12))., Conclusions: 5/23 patients with advanced carcinoma of the cardia had involved para-aortic nodes. This may have some prognostic value, but larger studies of D4 lymphadenectomy specimens is required.

Microsatellite instability (MIN) has been found both in advanced and early gastric cancer. To find out the step played by MSI in gastric carcinogenesis, links between RER+ phenotype and clinical and pathological aspects have been studied. In this work our purpose is to analyze the relationship between MIN+ advanced gastric cancer and prognosis at 5 years after radical surgery. We investigated 34 patients affected by gastric cancer who underwent R0 surgical resection from February 1991 to October 1994. After that, they underwent a four-monthly follow-up for a minimum of 5 years. Genetic abnormalities have been searched including (a) those occurring in common-type CIN carcinomas and (b) those characteristic of MIN cancers. DNA extraction showed the presence of microsatellite instability (MIN) in 9 (26%) of the samples (vs. 74% of chromosomal instability CIN); none of them was M+ (vs. 12% of CIN cancers). Recurrence occurred in 2 out of 9 of the MIN cancers (22%) and in 21 out of 25 CIN cancers (84%). In conclusion, our data suggest that advanced gastric cancers with mutator phenotype show a better outcome at 5 years than the CIN phenotype.