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Alberto Braghiroli,1 Fulvio Braido,2 Alessio Piraino,3 Paola Rogliani,4 Pierachille Santus,5 Nicola Scichilone6 1Department of Pulmonary Rehabilitation, Sleep Laboratory, Istituti Clinici Scientifici Maugeri, IRCCS, Veruno, NO, Italy; 2Department of Internal Medicine, Respiratory Diseases and Allergy Clinic, University of Genoa, Azienda Policlinico IRCCS San Martino, Genoa, Italy; 3Respiratory Area, Medical Affairs Chiesi Italia, Parma, Italy; 4Respiratory Unit, Department of Experimental Medicine, University of Rome “Tor Vergata”, Rome, Italy; 5Pierachille Santus, Department of Biomedical and Clinical Sciences (DIBIC), University of Milan, Milan, Italy; 6Department of Biomedicine and Internal and Specialistic Medicine (DIBIMIS), University of Palermo, Palermo, ItalyCorrespondence: Fulvio BraidoDepartment of Internal Medicine, IRCCS San Martino Genoa University Hospital, Genoa, ItalyEmail Fulvio.braido@unige.itAbstract: The topic of 24-hour management of COPD is related to day-to-night symptoms management, specific follow-up and patients’ adherence to therapy. COPD symptoms strongly vary during day and night, being worse in the night and early morning. This variability is not always adequately considered in the trials. Night-time symptoms are predictive of higher mortality and more frequent exacerbations; therefore, they should be a target of therapy. During night-time, in COPD patients the supine position is responsible for a different thoracic physiology; moreover, during some sleep phases the vagal stimulation determines increased bronchial secretions, increased blood flow in the bronchial circulation (enhancing inflammation) and increased airway resistance (broncho-motor tone). Moreover, in COPD patients the circadian rhythm may be impaired. The role of pharmacotherapy in this regard is still poorly investigated. Symptoms can be grossly differentiated according to the different phenotypes of the disease: wheezing recalls asthma, while dyspnea is strongly related to emphysema (dynamic hyperinflation) or obstructive bronchiolitis (secretions). Those symptoms may be different targets of therapy. In this regard, GOLD recommendations for the first time introduced the concept of phenotype distinction suggesting the use of inhaled corticosteroids (ICS) particularly when an asthmatic pattern or eosiophilic inflammations are present, and hypothesized different approaches to target symptoms (ie, dyspnea) or exacerbations. Pharmacotherapy should be evaluated and possibly directed on the basis of circadian variations, for instance, supporting the use of twice-daily rapid-action bronchodilators and evening dose of ICS. Recommendations on day and night symptoms monitoring strategies and choice of the specific drug according to patient’s profile are still not systematically investigated or established. This review is the summary of an advisory board on the topic “ 24-hour control of COPD and role of pharmacotherapy”, held by five pulmonologists, experts in respiratory pathophysiology, pharmacology and sleep medicine.Keywords: COPD, symptoms, dyspnea, night, sleep, follow-up, adherence, circadian LAMA, LABA, ICS

Resumo: A consciência de que a prática médica deve estar fundamentada na postura ética dos profissionais leva à crescente importância de um ensino de ética continuado e aprofundado, que ressalte os valores morais e humanos e o comprometimento social dos estudantes. Buscando adequar-se a esse novo paradigma, estudantes de Medicina da Universidade Federal da Bahia aceitaram a sugestão da criação, em novembro de 2000, de um grupo denominado Academética - Associação de Acadêmicos para o Estudo da Ética Médica e Bioética. Os objetivos traçados pela equipe são: continuar o contato com o conteúdo da disciplina Ética Médica, aprofundando e atualizando as discussões acerca de Ética Médica e Bioética, e desenvolver trabalhos ligados a este assunto. As discussões de temas são realizadas através do estudo de artigos, vídeos e estímulo à partidpação dos estudantes em congressos, palestras e afins. Desta forma, a Academética se constitui em mais uma ferramenta para que os alunos durante a graduação na faculdade de Medicina possam desenvolver o senso crítico e conhecimento acerca de assuntos que englobem a Ética Médica e Bioétia.

ABSTRACT Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. The Brazilian Society of Hepatology (SBH) published in 2015 its first recommendations about the management of HCC. Since then, new data have emerged in the literature, prompting the governing board of SBH to sponsor a single-topic meeting in August 2018 in São Paulo. All the invited experts were asked to make a systematic review of the literature reviewing the management of HCC in subjects with cirrhosis. After the meeting, all panelists gathered together for the discussion of the topics and the elaboration of updated recommendations. The text was subsequently submitted for suggestions and approval of all members of the Brazilian Society of Hepatology through its homepage. The present manuscript is the final version of the reviewed manuscript containing the recommendations of SBH.

ABSTRACT Objective: To test the hypothesis that undenatured type II collagen (UC-II) relieves pain, quality of life, and joint function in women aged from 60 to 80 years with knee osteoarthritis. Methods: 53 patients in the UC-II treatment group (for 90 days) and 52 in the control group (without UC-II) were evaluated at 1, 30, and 90 days regarding health-related quality of life, pain, and function with questionnaires, anthropometric data, alignment, range of motion, and radiographic analysis. Results: Quality of life increased significantly in the Physical domain in the treatment vs control group. Also, there was a difference between the first and the last evaluation on the pain visual analog scale (−3.8 ± 1.8 versus −1.3 ± 2.0) and on the WOMAC score (−9.5 ± 11.9 versus −1.3 ± 11.1). No variation in the temporal evolution of the Mental domain was found. Conclusion: Pain, joint stiffness, and quality of life (Physical domain) improved with the inclusion of UC-II for 90 days to the therapeutic toolbox for knee osteoarthritis in individuals aged 60 to 80 years. Level of evidence II, Comparative Prospective Study.

Introduction: Reactivation of hepatitis B virus (HBVr) is a problem still neglected worldwide. Objective: To assess knowledge of physicians regarding HBVr during immunosuppression including use of immunobiologics (IS/IB). Methods: Between August and October 2020, a national survey regarding current practices in HBVr prevention was sent to members of the Brazilian Societies of Hepatology, Gastroenterology, Hematology, Rheumatology, Oncology and Transplantation using a web-based approach. Results: 510 physicians answered the survey, mainly gastroenterologists (35%) and rheumatologists (31%). The majority had less than 20 years of clinical practice (62%). 91% reported to routinely request serology for HBV before IS/IB. To 90% of the interviewed doctors, in their clinical practice, serology is missing in less than 25% of their patients already using IS/IB. The most common serology panel requested (75%) is HBsAg, Anti-HBc and Anti-HBs. 76% recommend strategies to prevent HBVr for either HBsAg and/or anti-HBc-positive patients, however, 16% only prescribe to HBsAg-positive. 85% have an specialist on HBVr available for referring patients, but 30% start prevention strategies without the need for specialized evaluation. In this case, the preferred treatment options are entecavir (18%), tenofovir (17%) and lamivudine (6%). 88% reported good adherence of their patients to HBVr prevention strategy. Only 27% referred to maintain prevention strategy for at least 6 months after IS/IB interruption. Finally, 73% of the participants never experienced HBVr on their practice and 42% participated in educational activities about HBVr in the last 2 years. Conclusions: Compared to previous literature, Brazilian physicians seems to have a better compliance to international guidelines toward HBVr prevention. With the exception of duration of HBVr prophylaxis, medical knowledge on this field can be regarded as above average.

Simple Summary: COVID-19 has had a dramatic impact on new cancer diagnoses and the treatment of cancer patients. This study examines how the COVID-19 pandemic affected prostate cancer diagnosis, staging, and treatment in Reggio Emilia, Northern Italy. Using data from the Cancer Registry from 2018 to 2021, we found a significant drop in new prostate cancer diagnoses during 2020, the height of the pandemic. The number of new cases decreased by 31% in 2020, with a slight recovery of 5% in 2021. We also observed a shift towards more advanced stages and aggressive forms of prostate cancer, with fewer early-stage diagnoses and more cases of metastatic cancer. Despite these changes, treatments such as surgery and radiation therapy have remained constant. The pandemic disrupted an increasing trend of prostate cancer diagnoses seen before 2019, highlighting the need for ongoing diagnostic services and healthcare delivery, even during global health emergencies. Our study highlights the significant impact of COVID-19 on prostate cancer management and the importance of healthcare system resilience. The COVID-19 pandemic has caused delays in cancer diagnoses and reductions in treatments. The aim of this work is to evaluate the impact of the pandemic on prostate cancer by evaluating whether there has been a shift towards more aggressive (Gleason) and more advanced tumors (stage IV) and a decline in treatments. The study was conducted on 1123 cases of prostate cancer incident in the Province of Reggio Emilia, Northern Italy, in the period of 2018–2021. In 2020, there was a decline in new diagnoses of prostate cancer (−31%), followed by a slight recovery in 2021 (+5%). While Gleason 7 and 8–10 values remained constant, a significant decrease was recorded in stage I (38.7%, 41.6%, 35.5%, and 27.7%) and an increase in stage IV (13.1%, 13%, 15.4%, and 20%) cases in the years 2018, 2019, 2020, and 2021, respectively. However, there was no impact on surgical treatment (which remained constant at around 35%) and radiotherapy (around 39%). Our findings underline the profound impact of COVID-19 on prostate cancer management, highlighting the importance of healthcare resilience in the face of unprecedented disruptions. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal cancer remains a prevalent neoplasm affecting both genders. Despite advancements in screening techniques facilitating early detection, effective patient management remains paramount. This study investigates the impact of a multidisciplinary team (MDT) approach on patient outcomes. Results reveal a significant improvement in survival rates among MDT-followed patients compared to those lacking MDT oversight. Notably, no-MDT patients exhibited a twofold increase in mortality risk from both colon and rectal cancers. Furthermore, advanced age (>70 years) and advanced-stage disease (III and IV) emerged as pivotal risk factors. Consequently, prioritizing MDT intervention for these high-risk cohorts is imperative to optimize therapeutic strategies. Colorectal cancer emerged as the third most prevalent malignancy worldwide, affecting nearly 2 million individuals in the year 2020. This study elucidates the pivotal role of a multidisciplinary team (MDT) in influencing the prognosis, as measured by relative survival rates, depending upon the stage and age. Cases recorded in an Italian Cancer Registry between 2017 and 2018 were included. Relative survival was reported at 1 and 3 years after diagnosis comparing MDT vs. no-MDT approaches. During the study period, 605 CRCs were recorded while 361 (59.7%) were taken care of by an MDT. Compared to no-MDT, MDT patients were younger with earlier stages and received more surgery. One year after diagnosis, survival was 78.7% (90% in MDT vs. 62% in no-MDT); stratifying by stage, in the MDT group there was no survival advantage for stage I (97.2% vs. 89.9%) and II (96.8% vs. 89.4%), but an advantage was observed for stage III (86.4% vs. 56.9%) and stage IV (63.7% vs. 27.4%). Similar values were observed at 3 years where a marked advantage was observed for stages III (69.9% vs. 35.1%) and IV (29.2% vs. 5.1%). The univariable analysis confirmed an excess risk in the no-MDT group (HR 2.6; 95% CI 2.0–3.3), also confirmed in the multivariable regression analysis (HR 2.0; 95% CI 1.5–2.5). Despite the increase in the number of MDT patients in 2018 (from 50% to 69%), this does not correspond to an improvement in outcome. [ABSTRACT FROM AUTHOR]

Claudio Iovino,1 Giuseppe Giannaccare,2 Marco Pellegrini,2 Federico Bernabei,2 Mirco Braghiroli,1 Tomaso Caporossi,3 Enrico Peiretti1,4 1Department of Surgical Sciences, Eye Clinic, University of Cagliari, Cagliari, Italy; 2Ophthalmology Unit, S. Orsola-Malpighi University Hospital, University of Bologna, Bologna, Italy; 3Department of Ophthalmology, Ospedale Careggi, Firenze, Italy; 4Clinica Oculistica, San Giovanni di Dio Hospital, Azienda Ospedaliera Universitaria di Cagliari, Cagliari, ItalyCorrespondence: Enrico PeirettiEye Clinic, University of Cagliari, Via Ospedale 48, Cagliari 09124, ItalyTel|Fax +390706092319Email enripei@hotmail.comPurpose: To evaluate the efficacy and safety of combined 25-gauge (G) pars plana vitrectomy (PPV) with intravitreal dexamethasone implant (DXI) for the treatment of advanced stage epiretinal membrane (ERM).Methods: Forty consecutive pseudophakic eyes with idiopathic stage 3–4 ERM and intraretinal cysts were randomly assigned to two treatment groups. Twenty eyes underwent combined 25-G PPV, ERM peeling and slow-release DXI (DEX group), whereas 20 eyes underwent standard 25-G PPV with ERM peeling only (control group). Differences in postoperative best-corrected visual acuity (BCVA), intraocular pressure (IOP), central macular thickness (CMT) were evaluated.Results: In all patients, BCVA significantly increased at 1, 3 and 6 months after surgery compared to baseline (all p < 0.05), but at 3 and 6 months, the visual gain was higher in the DEX group (respectively, p = 0.036, p = 0.006). CMT was significantly lower in DEX group compared to control group at 3 and 6 months after surgery (respectively, p = 0.042, p = 0.003). There was no statistically significant difference in IOP change over the course of the follow-up between groups (p > 0.05).Conclusion: Combined 25-G PPV with DXI is associated with better anatomical and functional outcomes in patients with advanced stage ERM.Keywords: epiretinal membrane, intravitreal dexamethasone, macular pucker, intraretinal cysts

Abstract Cutaneous neoplasms frequently occur in leprosy, but there are few reports of the coexistence of leprosy and basal cell carcinoma in the same lesion. This case reports a 49-year-old male with an ulcerated plaque on the right lateral nasal wall, bright papules on the sternal region, and a blackened plaque on the right temporal region. The nasal and temporal lesions were diagnosed by histopathology as basal cell carcinoma and melanoma, respectively. The sternal lesions were excised with the repair of the “dog ear” which histopathological examination showed macrophages in the dermis parasitized with acid-fast bacilli, confirming the diagnosis of lepromatous leprosy with Fite-Faraco staining. This case report highlights the importance of referring the dog-ear specimen for histopathologic analysis.

Objective: The germline breast cancer gene (BRCA) mutation confers a lifetime high risk for breast cancer (BC) and bilateral prophylactic mastectomy is the procedure which allows the highest risk reduction rate. Among other techniques, lipofilling (LF) can be used for breast reconstruction of these patients. However, there are some oncological safety concerns on the subject. The purpose of this study was to assess the oncological risk of LF in BRCA healthy patients.Materials and Methods: A single institution case series was built including BRCA I/II mutated patients with no previous history of BC, who underwent bilateral prophylactic mastectomy followed by breast reconstruction with exclusive LF or combined with implants or latissimus dorsi flap. Data were collected regarding patient demographics, clinical information, reconstruction techniques used, and fat grafting details.Results: From September 1999 till November 2017, we identified 18 BRCA carriers with no history of BC who had undergone bilateral prophylactic mastectomy, followed by breast reconstruction with LF. A total of 36 LF procedures were performed following an implant or latissimus dorsi flap, or as an exclusive fat grafting breast reconstruction. The average number of LF sessions was 1.4 with a mean volume of 108.8cc per breast. Median follow-up was 33.0 months after mastectomy and 24.5 months after the last LF intervention; no patients were diagnosed with BC during follow-up.Conclusion: Germline BRCA mutation is a high-risk plight for BC. However, despite the limited follow-up, no BC was detected.

Pietro Emanuele Napoli1,* Mirco Braghiroli,1,* Claudio Iovino,1 Giuseppe Demarinis,1 Maurizio Fossarello1,21Department of Surgical Sciences, Eye Clinic, University of Cagliari, Cagliari, Italy; 2Clinica Oculistica, San Giovanni di Dio Hospital, Azienda Ospedaliera Universitaria di Cagliari, Cagliari, Italy*These authors contributed equally to this work Background: Effective and tolerable therapeutic strategies for patients with refractory persistent epithelial defects (PEDs) are limited and generally provide poor outcomes. This retrospective case review describes four refractory cases of PEDs associated with recurrent corneal erosions (RCEs) and dry eye disease (DED), which were successfully treated with cyclosporine eye drops.Methods: Patients were treated with cyclosporine A 0.05% eye drops twice a day for at least 12 months. At enrolling time, each patient was asked to suspend topical steroids or other eye drops used for ocular surface abnormalities with the exception of lubricants and eye washing. A complete evaluation of ocular surface symptoms was performed including the McMonnies Dry Eye Questionnaire, Ocular Surface Disease Index, slit-lamp biomicroscopy, fluorescein break-up time, the fluorescein staining of the cornea and conjunctiva (according to the Oxford grading system), the Schirmer I test, and the meibomian secretion after digital pressure application on the lids. This set of exams was carried out at baseline and repeated at all follow-up assessments.Results: All participants that did not benefit from previous therapies, including corticosteroids tapering schedule, showed an important improvement in the clinical picture after two months with topical cyclosporine medication. Moreover, after 12 months of continuous therapy, all patients showed a clinical improvement in DED signs and symptoms, related to the absence of new RCE episodes. The treatment was well tolerated, and no adverse effects were reported.Conclusion: Although a small number of cases were available of our analysis, the treatment with cyclosporine eye drops represents a promising approach in the management of refractory PEDs with associated ocular comorbidities, since it may reduce the RCE episodes and improve the tear film stability, in absence of systemic or local side effects.Keywords: dry eye disease, persistent epithelial defects, cyclosporine eye drops, recurrentcorneal erosion, corneal adhesion

Introduction: Violent and agitated patients pose a serious challenge for emergency medical services (EMS) personnel. Rapid control of these patients is paramount to successful prehospital evaluation and also for the safety of both the patient and crew. Sedation is often required for these patients, but the ideal choice of medication is not clear. The objective is to demonstrate that ketamine, given as a single intramuscular injection for violent and agitated patients, including those with suspected excited delirium syndrome (ExDS), is both safe and effective during the prehospital phase of care, and allows for the rapid sedation and control of this difficult patient population.Methods: We reviewed paramedic run sheets from five different catchment areas in suburban Florida communities. We identified 52 patients as having been given intramuscular ketamine 4mg/kg IM, following a specific protocol devised by the EMS medical director of these jurisdictions, to treat agitated and violent patients, including a subset of which would be expected to suffer from ExDS. Twenty-six of 52 patients were also given parenteral midazolam after medical control was obtained to prevent emergence reactions associated with ketamine.Results: Review of records demonstrated that almost all patients (50/52) were rapidly sedated and in all but three patients no negative side effects were noted during the prehospital care. All patients were subsequently transported to the hospital before ketamine effects wore off.Conclusion: Ketamine may be safely and effectively used by trained paramedics following a specific protocol. The drug provides excellent efficacy and few clinically significant side effects in the prehospital phase of care, making it an attractive choice in those situations requiring rapid and safe sedation especially without intravenous access. [West J Emerg Med. 2014;15(7):–0.]

Chromated copper arsenate-treated (cca) wood disposal faces environmental restrictions due to its toxicity, heavy metal leaching in storage sites, and greenhouse gas emissions during incineration. Thus, finding new management methods for this contaminated wood at the end of life is crucial. This study evaluated the effect of pyrolysis temperature (300, 400, and 500 °C), particle size, biochar yield, and the behavior of arsenic (As), chromium (Cr), and copper (Cu) during treated-wood pyrolysis. The highest biochar yield was obtained at 300 °C for fine particles. The biochar retention of heavy metals decreased with increasing pyrolysis temperature. At 300 °C, the highest biochar As, Cr, and Cu retentions were 76, 91, and 83%. At 500 °C, biochar only retained 43% of the As. Additionally, heavy metal leaching from the biochar exceeded the Environmental Protection Agency’s (EPA) maximum concentration limit of 5 mg/L. High-density polyethylene encapsulation of contaminated biochar reduced the leaching of As, Cr, and Cu by 96, 95, and 91%, respectively. Thus, combining pyrolysis and plastic encapsulation to produce a composite material could be a solution for reducing waste (conversion of CCA-wood into biochar) and for the safe disposal of contaminated wood.

Abstract Background Before the targeted therapies era, cytotoxic chemotherapy (CCT) was an option for advanced hepatocellular carcinoma (HCC), even with the lack of supporting evidence. Since the last decade, sorafenib has been established as the first-line therapy. Although new agents are being incorporated, CCT is still considered in regions where new drugs are not available or for patients who progressed through the approved therapies and remain in good clinical condition. We aimed to describe our experience regarding the use of CCT as second-line treatment after sorafenib. Methods A database of 273 patients was evaluated. Patients that received CCT after sorafenib progression were selected for the analysis. Descriptive statistics was used for categorical and continue variables. Median survival was estimated with Kaplan-Meier curves. Variables were found to be significant if the two-sided p value was ≤ 0.05 on multivariate testing using the Cox regression model. Results Forty-five patients received CCT; 33 (73.3%) had Child-Pugh classification A, and 34 (75.6%) had stage C according to the Barcelona Clinic Liver Cancer (BCLC) staging system. The most used regimen was doxorubicin in 25 patients (55.6%). Median overall survival (OS) was 8.05 months (95% confidence interval [CI] 2.73 – 9.88 months). The 6-month and 1-year survival probability was 52.4% and 27.36%, respectively. Eastern Cooperative Oncology Group performance status (ECOG PS) 0–1 and disease control with sorafenib was independently associated with better OS in patients treated with CCT. Any-grade toxicities were observed in 82.2% and grade 3–4 in 44.4% of the patients. Conclusion In accordance with previous studies, CCT had a notable rate of adverse events. The poor prognosis of this cohort suggests that CCT may not alter the natural history of HCC after sorafenib progression.

Microagulhamento ou indução percutânea de colágeno é procedimento dermatológico minimamente invasivo que usa agulhas para criar orifícios ou microcanais na pele. Tem como objetivo induzir formação de colágeno, neovascularização e produção de fatores de crescimento. Há aumento da procura por ser procedimento relativamente simples, com bom custo/benefício, seguro e com resultados satisfatórios. Trata áreas localizadas, e estudos estão se desenvolvendo para avaliar seu potencial em inflamações, discromias e fotodano. O uso terapêutico inclui tratamento de cicatrizes de acne, estrias, rítides, melasma, hiperidrose, alopecia. Atualmente tem sido usado para distribuição transepidérmica de ativos e vacinas.

Abstract: Amicrobial pustulosis of the folds is a chronic relapsing neutrophilic dermatosis characterized by sterile pustules compromising skin folds, scalp, face and periorificial regions. It predominantly affects women. Demodicosis is an inflammatory disease associated with cutaneous overpopulation of the mite Demodex spp., the pathogenesis of which is not completely established, but is frequently related to local immunodeficiency. A case of a young woman with amicrobial pustulosis of the folds, and isolated worsening of facial lesions, is reported; investigation revealed overlapping demodicosis. There was complete regression of lesions with acaricide and cyclin treatment. This case warns of a poorly diagnosed but disfiguring and stigmatizing disease, often associated with underlying dermatoses or inadvertent treatments on the face.