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Cancer immunotherapy is an emerging beneficial treatment for cancer that acts by activating the immune system to produce antitumour effects. In particular, immune checkpoint therapy has recently provided novel strategies for cancer treatments. Nevertheless, these new therapeutic approaches have introduced immune-related adverse events to clinical practice. In the elderly, checkpoint inhibitors might have limited efficacy because of immunosenescence. Limited literature data demonstrate a higher incidence of irAEs and an earlier discontinuation of immunotherapy in these patients. We report the case of an 89-year-old male patient with metastatic urothelial carcinoma, who presented with Grade 4 immune-related hepatitis after receiving pembrolizumab treatment.

Background The efficacy of pneumatic dilation (PD) in the management of achalasia has yielded variable results. The availability of high-resolution manometry led to the identification of 3 clinically relevant subtypes of achalasia, revealing the poor efficacy of PD in subtype III. Furthermore, PD showed a lower response rate in patients with subtype III compared to laparoscopic Heller myotomy and peroral endoscopic myotomy. This study aimed to investigate the short- and long-term efficacy, safety profile and side effects of PD with a "graded approach" in subtypes I and II achalasia.Methods We enrolled 141 patients (male 67, mean age=66 +/- 16.26 years) with achalasia (n=27 subtype I, n=74 subtype II and n=40 subtype III) between January 2010 and July 2020 at St. Orsola University Hospital, Bologna, Italy. We analyzed the data of patients with subtypes I and II, who underwent a graded-protocol PD. Short- and long-term clinical efficacy, complications and gastroesophageal reflux disease (GERD) were recorded.Results One month after graded protocol PD, 100% subtype I and 96.2% subtype II achalasia patients showed clinical remission. The PD procedure was completed without major complications in all patients. In the long-term follow up (median time: 56 months), 95.5% subtype I and 90% subtype II achalasia patients had an Eckardt score

Introduction: At the dawn of the 21st century, Covid-19 pandemic is testing national health care systems worldwide by leading to millions of Covid-19 patients and related deaths. Aim: to investigate the impact of the Covid-19 pandemic on socioeconomic determinants and health inequalities and to describe immediate action to inequality, morbidity and mortality from COVID-19.Methods: A literature review was conducted at the main search engines of scientific articles (Medline / Pubmed, Google Scholar) using specific keywords related to the topic. Publications both in Greek and English were taken into consideration. Results: Learnings from past pandemics have shown that socio-economic determinants of health have a significant effect in morbidity and mortality rates, and exacerbate health inequalities. In particular, it was observed that people from lower social classes ��� including people with poor finances or poorly educated, as well as immigrants, Roma and homeless people - are significantly more affected from the COVID-19 pandemic compared to people from higher social groups. Conclusion: The Covid-19 pandemic is expected to accelerate the spread of inequality by widening the gap between social groups and creating new forms of inequality. Specific state and citizen action is needed to stem the effects of the pandemic.

Introduction: At the dawn of the 21st century, Covid-19 pandemic is testing national health care systems worldwide by leading to millions of Covid-19 patients and related deaths. Aim: to investigate the impact of the Covid-19 pandemic on socioeconomic determinants and health inequalities and to describe immediate action to inequality, morbidity and mortality from COVID-19.Methods: A literature review was conducted at the main search engines of scientific articles (Medline / Pubmed, Google Scholar) using specific keywords related to the topic. Publications both in Greek and English were taken into consideration. Results: Learnings from past pandemics have shown that socio-economic determinants of health have a significant effect in morbidity and mortality rates, and exacerbate health inequalities. In particular, it was observed that people from lower social classes – including people with poor finances or poorly educated, as well as immigrants, Roma and homeless people - are significantly more affected from the COVID-19 pandemic compared to people from higher social groups. Conclusion: The Covid-19 pandemic is expected to accelerate the spread of inequality by widening the gap between social groups and creating new forms of inequality. Specific state and citizen action is needed to stem the effects of the pandemic.

Background The efficacy of pneumatic dilation (PD) in the management of achalasia has yielded variable results. The availability of high-resolution manometry led to the identification of 3 clinically relevant subtypes of achalasia, revealing the poor efficacy of PD in subtype III. Furthermore, PD showed a lower response rate in patients with subtype III compared to laparoscopic Heller myotomy and peroral endoscopic myotomy. This study aimed to investigate the short- and long-term efficacy, safety profile and side effects of PD with a “graded approach” in subtypes I and II achalasia. Methods We enrolled 141 patients (male 67, mean age=66 +/- 16.26 years) with achalasia (n=27 subtype I, n=74 subtype II and n=40 subtype III) between January 2010 and July 2020 at St. Orsola University Hospital, Bologna, Italy. We analyzed the data of patients with subtypes I and II, who underwent a graded-protocol PD. Short- and long-term clinical efficacy, complications and gastroesophageal reflux disease (GERD) were recorded. Results One month after graded protocol PD, 100% subtype I and 96.2% subtype II achalasia patients showed clinical remission. The PD procedure was completed without major complications in all patients. In the long-term follow up (median time: 56 months), 95.5% subtype I and 90% subtype II achalasia patients had an Eckardt score

Aim To investigate the Lyon Consensus Criteria impact on Ph-Impedance diagnosis of GERD and their relation to high resolution manometric tracing results. Background & Methods GERD is a complex disease with a heterogeneous symptom profile and a multifaceted pathogenic basis that defies a simple diagnostic algorithm or categorical classification. The Lyon Consensus defines parameters on esophageal testing that conclusively establish the presence of GERD and characteristics that rule out GERD. We retrospectively evaluated according the new criteria our patients underwent pH-Impedance one year before the publication of Lyon Consensus Criteria and analyzed the differences in relation to the older diagnostic criteria. Results 130 patients (56 M, median age 52,03 R18-77) Ph-impedance exams for suspected typical and atypical GERD were re-evaluated. According to Lyon criteria for conclusive evidence of GERD 15,38% of them were over-diagnosticated and 1,53% had inconclusive evidence of the disease using the past criteria. In the evaluation of 94 patients with typical symptoms 23,4% were over-diagnosticated in according to the past diagnostic criteria. Statistical analysis of manometric values of the patients highlight that LES basal pressure (median 108.95, R38.7-283.4) (p=0,049) and UES residual pressure (median 7.8 R0.6-63.5) (p=0,003) significantly predict the Lyon criteria pH-impedance outcome. Analysis of manometric values of the patients with typical symptoms revealed that LES residual pressure (median 5,21 R0,1-20,7) (p=0,007) and Total Number of refluxes (median 28,03 R1-122) (p=0,013) significantly predict the Lyon criteria pH-impedance outcome. Conclusion Lyon Consensus Criteria significantly changes the pH-impedance diagnosis in patients undergoing testing for suspected GERD. In patients with typical symptoms new criteria allow not to overdiagnose 25% of GERD patient. Manometric values analysis significantly correlates and predict the Lyon criteria pH-impedance outcome.

Esophageal achalasia is a primary motility disorder characterized by impaired lower esophageal sphincter relaxation and absence of esophageal peristalsis leading to impaired bolus transit, manifested with symptoms such as dysphagia, regurgitation, retrosternal pain, and weight loss. The standard diagnostic tool is esophageal manometry which demonstrates incomplete relaxation of the lower esophageal sphincter and impaired esophageal peristalsis. Recently, a new advanced technique, high-resolution manometry (HRM) with the addition of pressure topography plotting, using multiple sensors to capture the manometric data as a spatial continuum, allows a detailed pressure recording of the esophageal motility. This technique, currently the gold standard for the diagnosis of achalasia, has led to a subclassification of three manometric types that seem to have different responsiveness to treatment. Because its pathogenesis is as yet unknown, achalasia treatment options are not curative. Type II achalasia patients respond better to treatment compared to those with types I and III. Low-risk patients with type I or II achalasia have good outcome with both graded pneumatic dilatations and laparoscopic Heller myotomy, while type III achalasia patients respond better to laparoscopic Heller myotomy. Although, type III achalasia patients responds less in comparison to types I and II to laparoscopic Heller myotomy. Peroral endoscopic myotomy is a promising new technique but long-term follow-up studies for its safety and efficacy must be performed. This article reviews the current therapeutic options, highlighting the impact of HRM to predict the outcome and the new insights for the treatment of achalasia.

Background: Chronic rhinitis is a diffuse disease with a prevalence of 40% in western world. Vasomotor rhipopathy rappresents the main cause of chronic rhinitis and is classified in Allergic Rhinitis (AR) and Non Allergic Rhinitis (NAR) (AR/NAR = 2.4/1). Nasal cytology allows to identify the different NAR sub-types on the basis of the inflammatory cell infiltrate: nonallergic rhinitis with neutrophils (NARNE), nonallergic rhinitis with eosinophils (NARES), nonallergic rhinitis with mast cells (NARMA) and nonallergic rhinitis with eosinophils and mast cells (NARESMA). NAR etiopathogenesis is not wet clarified and for NARNE subtype has been suggested GERD as one of the etiopathogenetic factors. Aim: To evaluate the role of GERD on patients affected by NARNE. Materials and methods: Fifty one consecutive patients (mean age 51.29 ± 15.69 years; M/F = 18/33) referred to our ENT unit for nasal symptoms such as: rhinorrhea, sneezing, and postnasal drip, presenting non allergic rhinitis were enrolled in the study. Visual analogue scale (VAS) for nasal symptoms, rhinomanometry, skin prick test and nasal cytology were performed. Exclusion criteria were environmental irritant exposure and/or a positive skin prick test. All the patients performed a gastroenterological evaluation, a high resolution esophageal manometry and a 24 hour pH-Impedance monitoring. Results: Twenty five (49%) patients tested positive at nasal cytology for the presence of neutrophils in nasal mucosa (neutrophils >50% with absent spores and bacteria) (NARNE) while the remaining twenty six (51%) were negative. Apart from drainage, no significant differences were observed between the two groups with regard to symptoms (Table 1). At the univariate analysis, the only significant difference between the groups was higher proportion of patients in the group with neutrophilic rhinitis testing positive at pH-impedance and with a less intense drainage (Table 1).The logistic regression analysis confirmed the significant relationship between being positive at pH-impedance and having a neutrophilic rhinitis (P < 0.0001, Table 2), while a stronger drainage was more likely associated with a non-neutrophilic rhinitis (P < 0.0001, Table 2). Table 1 NARNE N = 25 NON NARNE N = 26 P Age 46.08 (17.66) 56.30 (11.82) 0.0249 Sex 14F/6M 19F/7M Ns Nasal Obstruction 4.36 (3.25) 3.57 (3.47) Ns Pruritus 0.4 (1) 1.03 (1.58) Ns Rinorrhea 2.92 (3.21) 2.30 (2.57) Ns Drainage 3.28 (3.40) 5.57 (2.80) 0.0175 Starnuti 0.84 (1.79) 1.76 (2.02) Ns Positive pHmetry 20 5

Koufman Chronic Cough Index™ (KCCI) (R = Reflux, N = Neurogenic) Ratio. (DOCX 14 kb)

Open-pore aluminium foams are of interest in thermal management of power electronics due to their large specific surface area, low weight and relatively high thermal conductivity. The replication process is a low-cost and simple foam manufacturing method that offers many opportunities for the investigation of the influence exerted by the microstructure (porosity, pore size) and geometry or their combination in the performance of metal foams in heat-exchange applications. In this study, we explored replicated aluminium foams as a part of an integrated heat sink manufactured in one step that seamlessly combines metal and ceramic phases. Replicated aluminium foams were manufactured and tested first under natural and then under forced convection. A dedicated test apparatus was built to test these samples under both natural and forced convection, using the guarding ring technique. In the case of natural convection, the aluminium foams had different pore sizes (125-180 µm, 400-450 µm and 5 mm), porosities (78 to 86%) and geometry (disk, cylinder and finned structures). In all cases, replicated aluminium foams were found to dissipate the same amount of heat as their bulk aluminium (alloy) equivalents. The thermal heat exchange performance of replicated microcellular aluminium was also measured under forced convection. The test rig was modified to measure the pressure drop and volumetric air flow in a cylindrically symmetric jet impingement configuration. Foams of different pore size (125-180, 400-450 and 900-1300 µm), porosity (between 75 and 85 %), height (1 and 2.8 cm) and infiltrated at various pressures (between 2.7 and 70 bars) were manufactured for thermal testing, all having a hollow central channel, through which air is injected at a range of flow rates. The results show that within the covered parameter range foams of higher porosities, larger pore sizes and lower infiltration pressures dissipate more heat at lower cost in terms of pumping power. Shorter heights also dissipate more heat for a given volumetric flow but do so at the cost of an increased pressure drop and hence greater pumping power expenditure. A numerical model, developed and written by Dr. D. Ingram, using the finite-volumes technique, was employed to elucidate how the various parameters influence the heat transfer. The model solves the Darcy-Forchheimer formulation of fluid flow in porous media, which is then coupled to a convective/conductive heat transfer model of the same structure. These simulations were used to perform parametric studies on the influence of height and pore size with regard to the thermal behaviour of replicated foams. Furthermore, the model was benchmarked against the experimental results; overall, despite some discrepancies with measured temperature profiles, the model captures data trends well, and provides insight on the physical phenomena that underlie the experimental data and observations. In particular, the presence and influence of recirculating air flow along the inner portion of the heat exchanger structures was identified. Finally, we successfully fabricated the proposed integrated multimaterial structure and tested it under forced convection, using the same conditions as the replicated aluminium foams. Results demonstrate that this type of structures can be effectively used to cool power electronics.

Voice Institute of New York Chronic Cough Form. (DOCX 13Â kb)

Voice Institute of New York Chronic Cough Form. (DOCX 13Â kb)

Koufman Chronic Cough Index™ (KCCI) (R = Reflux, N = Neurogenic) Ratio. (DOCX 14 kb)