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• The prevalence of sleep disturbances increases with aging; • Sleep apnea and insomnia symptoms were the most predominant sleep complaints in the edlderly; • Older women reported more insomnia symptoms and worse sleep quality than men. • Validated sleep questionnaires may assist in the screening of sleep disorders; This study aimed to investigate the prevalence of sleep problems in older subjects, considering sex and age differences. Subjects admitted to a geriatrics clinic underwent a medical visit and completed a battery of questionnaires assessing sleep quality, insomnia, sleep apnea risk, excessive daytime sleepiness (EDS), restless legs syndrome (RLS), chronotype, depression and global cognition. Fifty-eight subjects (58.6 % women, mean age 77.36±6.07) were included. The most predominant sleep-related complaint was poor sleep quality (36.2 %), followed by sleep apnea risk (34.5 %), insomnia symptoms (25.9 %), EDS (15.5 %) and RLS (12.1 %). Older women reported more insomnia, poorer sleep quality and depressive symptoms than males. Patients aged ≥ 75 years old had more comorbidities and higher sleep apnea risk compared to those under 75 years old. Sleep problems are frequent in older adults, requiring their screening and treatment for possibly improving well-being and reduce the burden of neuropsychiatric and medical comorbidities. [ABSTRACT FROM AUTHOR]

The advantages of immediate implant placement for patients include a reduced number of surgical procedures and a shorter overall treatment time. Disadvantages include a higher risk of aesthetic complications. The aim of this study was to compare xenogeneic collagen matrix (XCM) versus a subepithelial connective tissue graft (SCTG) used for soft tissue augmentation in combination with immediate implant placement without provisionalization. Forty-eight patients requiring a single implant-supported rehabilitation were selected and assigned to one of two surgical procedures: immediate implant with SCTG (SCTG group) or immediate implant with XCM (XCM group). Marginal changes in the peri-implant soft tissue and the facial soft tissue thickness (FSTT) were assessed after 12 months. Secondary outcomes included peri-implant health status, aesthetics, patient satisfaction, and perceived pain. All of the implants placed were successfully osseointegrated, resulting in 1-year survival and success rates of 100%. The patients in the SCTG group had a significantly lower mid-buccal marginal level (MBML) recession (P = 0.021) and a greater increase in FSTT (P < 0.001) than the patients in the XCM group. Using xenogeneic collagen matrix during immediate implant placement significantly increased FSTT from the baseline, leading to good aesthetic and patient satisfaction results. However, the connective tissue graft yielded better MBML and FSTT results. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) mostly develops in a cirrhotic liver and represents a serious public health problem. Liver transplantation (LT) is a therapeutic option for HCC that offers to patients a long-term survival. The aim is to investigate depression and anxiety in HCC patients evaluated for LT. Retrospective study (N=179) at liver disease clinic on patients with a diagnosis of cirrhosis evaluated for LT. Inclusion criteria: completion of the psychological evaluation for eligibility to transplantation. The sample was divided in two groups: HCC (89/179; 49.7%) and no-HCC. Patients underwent a psychological evaluation with clinical interviews and psychological assessment with self-report questionnaires for depression (BDI-II), anxiety (BAI) and general psychological problems (SCL-90). Descriptive analyses and linear regression analyses were performed. Among the 179 patients, 84.9% were men, the mean age was 58 years. HCC group has lower depression (p <.01), anxiety (p <.05), SCL-Somatization, SCL-Depression, and SCL-Anxiety (p <.05) than no-HCC group. They also have a lower severty of liver disfunction (MELDNa) (p <.001). Univariate linear regression analysis highlighted a correlation between depression (BDI-II) and respectively: age, gender, HCC, MELDNa class and psychopathological anamnesis. Multivariate linear regression analysis [covariate: male gender OR -3.6 (95% CI -7.11– -0.21); psychopathological anamnesis OR 6.3 (95% CI 3.87 – 8.77), HCC OR -4.3 (95% CI -6.88 – -1.80); p < 0.05] highlighted that depression is positively associated with psychopathological history and inversely with HCC and male gender. Counterintuitively, patients with HCC show less depression/anxiety than patients without HCC, probably because of multiple loco-regional or systemic oncologic therapies. HCC and male gender have a significant effect on depression. HCC patients may not perceive the severity of their liver disease and lack of insights on it, therefore it could be important to enhance their compliance to the transplant programs. [ABSTRACT FROM AUTHOR]

Start-ups in dynamic industries frequently pivot their focus, which can help them develop a clear strategic position and subsequently generate a competitive advantage. Whether to pivot or persevere becomes a real-time, critical, and multifaceted decision involving the founder, firm, and environment, but little is known about this complex interplay. Through an explorative case study, we tracked the founding, survival, and growth of Codigames, a high-performing Valencia-based mobile gaming start-up. We combine entrepreneurial leadership, decision-making, and perspective-taking theories to generate insight into critical moments in the start-up's lifepath, contributing to research on the contextualisation of entrepreneurship decision-making under uncertainty. • Start-ups pivot for competitive advantage. • Entrepreneurial leadership shapes strategic change. • Perspective-taking aids decision-making in uncertainty. • Mobile-gaming industry's rapid growth post-COVID-19. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is an increasingly common cancer with a persistently poor prognosis, and only approximately 20% of patients are clearly anatomically resectable at diagnosis. Historically, a paucity of effective therapy made it inappropriate to forego the traditional gold standard of upfront surgery in favour of neoadjuvant treatment; however, modern combination chemotherapy regimens have made neoadjuvant therapy increasingly viable. As its use has expanded, the rationale for neoadjuvant therapy has evolved from one of 'downstaging' to one of early treatment of micro-metastases and selection of patients with favourable tumour biology for resection. Defining resectability in PDAC is problematic; multiple differing definitions exist. Multidisciplinary input, both in initial assessment of resectability and in supervision of multimodality therapy, is therefore advised. European and North American guidelines recommend the use of neoadjuvant chemotherapy in borderline resectable (BR)-PDAC. Similar regimens may be applied in locally advanced (LA)-PDAC with the aim of improving potential access to curative-intent resection, but appropriate patient selection is key due to significant rates of recurrence after excision of LA disease. Upfront surgery and adjuvant chemotherapy remain standard-of-care in clearly resectable PDAC, but multiple trials evaluating the use of neoadjuvant therapy in this and other localised settings are ongoing. [ABSTRACT FROM AUTHOR]

Background: Ictal piloerection (IP) is a rare manifestation of focal epilepsy. Autoimmune limbic encephalitis (LE) and malignant brain tumours are the most frequent recognized aetiologies.Methods: We selected all patients diagnosed with LE in our Institute from 2004 to 2020 and manifesting with IP. We performed a literature review on LE patients presenting IP.Results: Of 15 patients diagnosed with LE (13.3%), two manifested IP as prominent ictal feature. One of them also had stiff-limb syndrome. Video-EEG documented ictal discharges from the right temporal regions with concomitant sympathetic skin response (SSR) recording. Antibody testing showed elevated serum and CSF titres of GAD65 antibodies (Ab), in both cases. Despite a combination of several anti-seizure medications and first- and second-line immunotherapy, they showed a poor clinical outcome after 2 and 9 years of follow-up, respectively. The literature review yielded 13 papers reporting 26 LE cases with IP. LGI1 Ab were the most frequently associated (73.1%) followed by VGKC-complex (7.7%), GAD65 (7.7%), NMDAr (3.8%), Ma2 (3.8%) and Hu (3.8%) Ab. Cases with LGI1 Ab showed a good response to immunotherapy.Discussion and Conclusion: The prevalence of IP in our LE cohort was of 13.3%, higher than expected. According to the literature review, most cases were associated with LGI1 Ab and showed a good response to immunotherapy. With the contribution of our cases, GAD65 emerged as the second most frequently detected Ab, showing a poor outcome. Our findings widen the spectrum of IP-associated Ab, with the respective prognostic implications. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to assess the sleep-wake pattern in patients with epilepsy compared to controls.Methods: Patients with epilepsy and controls underwent a 14-day actigraphic recording to evaluate the rest-activity cycle. A sleep medicine interview was performed to exclude conditions interfering with the sleep-wake cycle in both patients and controls. Patients presenting seizures during the actigraphic recording were excluded. Daytime activity, nocturnal sleep, and non-parametric circadian rhythm activity (NPCRA) were analysed.Results: Twenty-two patients (mean age 49.5 ± 19.84 years; 50% female) and 17 controls were included. Patients showed lower sleep efficiency and longer sleep latency than controls. NPCRA analysis showed lower inter-daily stability and higher intra-daily variability in patients, who also presented lower daytime activity and a longer central phase measure (CPM) than controls.Conclusions: Patients showed a significant alteration of the sleep-wake pattern, featured by lower synchronization and higher fragmentation of the rest-activity rhythm. Moreover, patients showed a delayed CPM compared with controls, corresponding to an evening chronotype tendency. Nocturnal sleep alteration and lower daytime activity were also evident. Therefore, patients with epilepsy present an alteration of the sleep-wake pattern and clinicians should increase their awareness about circadian rhythmicity dysregulation in epilepsy. [ABSTRACT FROM AUTHOR]

Treatment of inflammatory bowel disease (IBD) frequently requires administration of immunosuppressive therapies, which increases susceptibility to a number of infectious pathogens. However, many infections can be prevented by correct and appropriate utilization of vaccinations. While several guidelines have been published on vaccination schedules in patients with IBD, vaccination rates remain suboptimal and even lower than those in the general population. This is due to many factors including poor awareness of the importance of vaccines by gastroenterologists and general practitioners as well as potential prejudices of patients regarding the safety and benefits of vaccines. With the aim of increasing awareness about the key role of immunization in the management of patients with IBD, the present review examines the existing literature relating to the main vaccinations and their application in these patients. We also summarize current evidence in order to provide clinicians with an easy source of reference for the principal recommendations for prevention of infectious diseases in patients with IBD. In addition, the recommendations about traveling for IBD patients are briefly explored. Lastly, since it is important for gastroenterologists to be aware of recommendations on vaccination, we recommend implementing educational programs to ensure compliance with current guidelines. [ABSTRACT FROM AUTHOR]

Background and Aims: Restriction measures adopted during the Coronavirus Disease-19 pandemic favored unhealthy behaviors. Tele-health offered the opportunity to pursue alternative ways of chronic diseases management. This retrospective study sought to determine the effects of a telehealth counselling intervention during the lockdown to children and adolescents with obesity previously engaged in a family-based secondary care program in an outpatient clinic of South Italy.Methods and Results: 117 out of 156 patients participated to the tele-health intervention. Participants underwent videocalls with each component of the multidisciplinary team to receive support in adopting adequate dietary habits and to practice exercise at home. They were included in a closed social group to watch age-adapted tutorials on healthy habits. 75 patients returned to the Center after the end of the lockdown, while only 7 patients who did not participate to the videocalls, took part to the follow-up. Body Mass Index and body composition were assessed in all these patients. BMI z score did not increase in both groups. However, a significant increase of fat mass was observed in the non-participating group (0.046), while the intervention group showed an increase of fat free mass (p < 0.000).Conclusion: Notwithstanding the limited sample size, the telehealth intervention allowed the maintenance of baseline weight status in participants, with an increase of fat-free mass. As the CoViD-19 pandemic moves forward, the increasing adoption of the new technologies may help the continuity of care, even in pediatric obesity treatment. [ABSTRACT FROM AUTHOR]

Myotonic dystrophy type 1 (DM1) is a rare inherited neuromuscular disease associated with insulin resistance, and its association with metabolically associated fatty liver disease (MAFLD) has never been explored in prospective studies. The aim of this study was to assess the clinical features of MAFLD in DM1 patients. We investigated the prevalence and the diagnostic features of MAFLD in a cohort of 29 outpatient fully characterized DM1 patients; afterward, we compared the selected cohort of DM1-MAFLD individuals with a propensity-matched cohort of non-DM1-MAFLD 13/29 (44.83%) DM1 patients received a clinical diagnosis of MAFLD. Compared to DM1 patients with normal liver, DM1-MAFLD individuals showed a higher male prevalence (p = 0.008), BMI (p = 0.014), HOMA score (p = 0.012), and GGT levels (p = 0.050). The statistical comparison showed that the DM1-MAFLD group had a more severe MAFLD according to the FIB4 score than non-DM1-MAFLD patients. This association of a more severe form of liver disease with DM1 remained significant after logistic regression analysis (OR: 6.12, 95% CI 1.44- 26.55). [ABSTRACT FROM AUTHOR]

Distal Cholangiocarcinoma (dCCA) represents a challenge in hepatobiliary oncology, that requires nuanced post-resection prognostic modeling. Conventional staging criteria may oversimplify dCCA complexities, prompting the exploration of novel prognostic factors and methodologies, including machine learning algorithms. This study aims to develop a machine learning predictive model for recurrence after resected dCCA. This retrospective multicentric observational study included patients with dCCA from 13 international centers who underwent curative pancreaticoduodenectomy (PD). A LASSO-regularized Cox regression model was used to feature selection, examine the path of the coefficient and create a model to predict recurrence. Internal and external validation and model performance were assessed using the C-index score. Additionally, a web application was developed to enhance the clinical use of the algorithm. Among 654 patients, LNR (Lymph Node Ratio) 15, neural invasion, N stage, surgical radicality, and differentiation grade emerged as significant predictors of disease-free survival (DFS). The model showed the best discrimination capacity with a C-index value of 0.8 (CI 95 %, 0.77%–0.86 %) and highlighted LNR15 as the most influential factor. Internal and external validations showed the model's robustness and discriminative ability with an Area Under the Curve of 92.4 % (95 % CI, 88.2%–94.4 %) and 91.5 % (95 % CI, 88.4%–93.5 %), respectively. The predictive model is available at https://imim.shinyapps.io/LassoCholangioca/. This study pioneers the integration of machine learning into prognostic modeling for dCCA, yielding a robust predictive model for DFS following PD. The tool can provide information to both patients and healthcare providers, enhancing tailored treatments and follow-up. [ABSTRACT FROM AUTHOR]

Despite the increased use of minimally invasive approaches for pancreatoduodenectomy (PD), the association between surgical approach and venous thromboembolism (VTE) risk is still unknown. This study aims to compare VTE rates following open (OPD) and minimally invasive pancreatoduodenectomy (MIPD). MEDLINE, Web of Sciences and EMBASE databases were searched to identify eligible studies. Studies were considered suitable if the incidence of postoperative VTE in open and minimally invasive (laparoscopic or robotic) pancreatic surgery was reported. The review was conducted following the PRISMA guidelines. Five studies including 12 984 patients met the inclusion criteria and were considered for meta-analysis. A total of 11 060 patients underwent OPD and 1924 MIPD. Overall, patients who underwent OPD had a lower rate of VTE compared to MIPD (3.6 % vs 4.6 %, OR (95 % CI) = 0.66 (0.52–0.85), p < 0.001). Subgroup analysis showed similar results for pulmonary embolism (PE) (1.1 % in OPD vs 1.9 % in MIPD, OR (95 % CI) = 0.54 (0.36–0.80), p 0.002) and deep venous thrombosis (DVT) (1.3 % in OPD vs 3.1 % in MIPD, OR (95 % CI) = 0.48 (0.29–0.79), p 0.004). Patients who undergo minimally invasive pancreatoduodenectomy have a higher incidence of postoperative VTE when compared to open pancreatoduodenectomy. [ABSTRACT FROM AUTHOR]

The accurate measurement of blood pressure (BP) is an important prerequisite for the reliable diagnosis and efficient management of hypertension and other medical conditions. Office Blood Pressure Measurement (OBP) is a technique performed in-office with the sphygmomanometer, while Ambulatory Blood Pressure Monitoring (ABPM) is a technique that measures blood pressure during 24h. The BP fluctuations also depend on other factors such as physical activity, temperature, mood, age, sex, any pathologies, a hormonal activity that may intrinsically influence the differences between OBP and ABPM. The aim of this study is to examine the possible influence of sex on the discrepancies between OBP and ABPM in 872 subjects with known or suspected hypertension. A significant correlation was observed between OBP and ABPM mean values calculated during the day, night and 24h (ABPMday, ABPMnight, ABPM24h) in both groups (p<0.0001). The main finding of this study is that no difference between sexes was observed in the relation between OBP and mean ABMP values except between systolic OBP and systolic ABPM during the night. In addition, this study showed a moderate correlation between BPs obtained with the two approaches with a great dispersion around the regression line which suggests that the two approaches cannot be used interchangeably. [ABSTRACT FROM AUTHOR]

As a chronic inflammatory disease, ulcerative colitis has significant negative impact on the quality of life (QoL) of patients. Since the disease affects many aspects of QoL, comprising multiple domains, treatments that induce and maintain remission can provide benefits beyond hard clinical endpoints. Effective treatment of ulcerative colitis can restore QoL and return it to normal or near normal levels. Biological therapies have shown consistent improvement in the QoL of patients with ulcerative colitis during the induction phase, with benefits that are generally maintained in the long-term. Current medical treatment options broadly comprise aminosalicylates, corticosteroids, thiopurines, and calcineurin inhibitors, as well as biologic therapies. Conventional therapies do not always adequately control disease in a sizeable portion of patients, while anti-TNF antibodies are associated with several issues such as contraindications, intolerance, primary non-response, and loss of response in some patients. JAK inhibitors have been associated with clinical improvements in disease manifestations and long-term improvement in QoL outcomes. However, additional studies are needed to better understand the comparative effects of different treatments on QoL and patient preferences for therapy. Herein, the available evidence is reviewed regarding the impact of various treatments on QoL in patients with moderate to severe ulcerative colitis. [ABSTRACT FROM AUTHOR]

Dental implant placement is a predictable therapy for replacing teeth. Nevertheless, mechanical, biological, and aesthetic complications frequently occur. The aim of this study was to compare the clinical outcomes of a xenogeneic collagen matrix (XCM) used at the time of implant placement as an alternative to a subepithelial connective tissue graft (SCTG), for soft tissue augmentation. This was a prospective clinical trial with 12 months of follow-up. In the control group, soft tissue augmentation at the time of implant placement was performed with a SCTG, while in the test group, a XCM was employed. At 12 months postoperative, all xenografts showed no postoperative complications. In both groups, a significantly greater thickness was observed on the buccal and occlusal sides from preoperative to 3 months postoperative (P < 0.05). No statistically significant difference in pink aesthetic score (P = 0.379, 6 months postoperative) or marginal bone loss (P = 0.449 at 3 months postoperative, P = 0.778 at 6 months postoperative) was observed between the groups. Statistically significant differences in pain perceived by the patients (P < 0.0001) and the time to complete the surgical procedure (P = 0.0008) were detected. At 12 months after surgery, XCM provided similar clinical results in terms of soft tissue augmentation on the buccal and occlusal sides as compared with the SCTG. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is the main cause of chronic liver disease and ranges from simple steatosis to nonalcoholic steatohepatitis. Recently, a platelet role in NAFLD pathogenesis and progression has been reported in mouse models and in patients. We investigated whether platelets are involved in liver and systemic inflammation processes in NAFLD. In this exploratory study we recruited 24 consecutive patients with biopsy-proven diagnosis of NAFLD and 17 healthy volunteers. We measured plasma levels of inflammatory markers by ELISA. We investigated hemostatic and inflammatory transcripts in circulating platelets and leukocytes from NAFLD patients. We analyzed platelet and neutrophil extracellular traps (NET) accumulations in liver sinusoids using CD42 and H3 citrullinated histones immunohistochemical staining on liver biopsies. NAFLD patients had increased inflammation markers and lipolysaccharides plasma levels. We found significant increase of inflammatory transcripts in circulating platelets and not in leukocytes of NAFLD subjects compared with healthy controls. We demonstrated increased intrahepatic platelet accumulation that correlated with NAFLD activity score (NAS) score and intrahepatic neutrophil extracellular traps (NET) formation in liver biopsies of NAFLD patients. NET formation was higher in livers with higher NAS and inflammation scores. The presence of low-grade systemic inflammation and proinflammatory changes of circulating platelets indicate that platelets participate on systemic inflammatory changes associated with NAFLD. Liver platelet accumulation and liver NET formation, together with low-grade endotoxemia, suggest that platelets may act to protect the liver from invading microorganisms by favoring local NET formation. [ABSTRACT FROM AUTHOR]

Older age represents a major risk factor for developing colorectal cancer and the disease disproportionately affects patients older than 60 years of age. However, knowledge regarding the optimal management of older patients with metastatic colorectal cancer (mCRC) remains limited. The challenge of treating older patients arises in tailoring treatments to a heterogeneous cohort whilst adjusting for individuals with a wide variation of physiological reserve, a reduced tolerance to treatment side-effects and morbidity, and often different priorities as compared with younger patients. Data from the published literature supports the premise that older age alone is not an acceptable determinant of treatment options. In particular, patients aged 65–70 years with mCRC ought to be considered similarly to younger patients and patients aged 70–74 also stand to benefit from both hepatic resection and systemic therapy notwithstanding the higher rates of morbidity and mortality. Patients aged 75–79, and with sufficient physiological reserve ought to be considered for curative treatment options which are proportional to the extent of metastatic disease. Meanwhile, in patients aged ≥80 years, life-extending or life-enhancing benefit ought to be demonstrable prior to embarking upon major surgery as a curative treatment option. Older patients who meet the physiological eligibility criteria to enter clinical trials of systemic chemotherapy appear to gain similar benefit as younger patients and should not be excluded on the basis of age alone. Clinical trials that are specifically designed for older patients are feasible and could yield valuable information to guide clinical practice. [ABSTRACT FROM AUTHOR]

As the population of western countries is aging, the number of patients diagnosed with cancer is growing. Therefore older people, more susceptible to develop pancreatic malignancy, will likely represent the prototype of a pancreatic cancer patient in the near future. Diagnostic modalities utilised for younger patients are also applicable for older individuals. There is accumulative evidence that biological age is not an independent factor predicting poor outcome in elderly patients with resectable disease undergoing surgery, however increased postoperative morbidity and mortality within the elderly group has also been reported. Adjuvant chemotherapy should be offered in all patients with good performance status regardless of their age. Palliative measures for unresectable tumours including relief from biliary and duodenal obstruction as well as chemotherapy should be considered in non-frail patients with reasonable life expectancy. Palliative chemotherapy options are FOLFIRINOX or gemcitabine/nab-paclitaxel for patients with good performance status (0–1) and gemcitabine alone for patients with performance status 2–3. The cornerstone for improving the outcomes of the elderly age group is careful patient selection and perioperative optimization of those who have indication for surgery. Patients and their carers should be involved in the decision making process with emphasis on the expected functional recovery after the proposed treatment modality. The presence of geriatricians in the multidisciplinary team meetings is crucial in order to identify the optimal treatment pathway for elderly patients. Geriatric input regarding peri-habilitation pathways to improve surgical outcomes, to decrease mortality and to expedite patients' functional recovery is highly recommended. • Diagnostic modalities should be the same for elderly patients as in younger population. • Age is not an independent contraindication for surgery. • Geriatric specialists have a crucial role in designing the appropriate management and in optimising the patients for surgery, chemotherapy or both. • FOLFIRINOX, gemcitabine and nab-paclitaxel are well tolerated by the elderly population. • Holistic care is recommended to facilitate elderly patients' functional recovery after treatment. [ABSTRACT FROM AUTHOR]

Older age is a risk factor for the development of HCC. However, the treatment options available for older patients with HCC, their safety, efficacy and utility, are poorly understood resulting in challenging decision-making. In this review, we aim to report the best available evidence to facilitate optimal decision making for older patients with HCC. We report that surgical resection for HCC is equally safe (90-day mortality ~3%) and effective (five-year disease free survival ~40%) for older patients as it is for younger patients. Five-year survival after ablation therapy for HCC is in excess of 50% in older patients, whilst morbidity rates are in the region of 3%. Survival rates of 30% after chemoembolisation reflects its role as a non-curative treatment. Transplantation is an option that may be helpful for a minority of patients, but the high risks of in-hospital mortality and lower likelihood of receiving a transplant should be duly considered before committing to this approach. We therefore advocate an individualised assessment for older patients based on these risk profiles and probabilities of optimal outcomes. In patients with a projected life-span ≥ 3 years, and who have sufficient physiological and functional reserve, surgical resection should be the treatment of choice. Patients with a projected life-span < 3 years are better served with loco-regional therapies, and tumour size, at a threshold of 3 cm, should guide the choice between ablation and chemoembolisation therapies. [ABSTRACT FROM AUTHOR]

Advanced hepatocellular cancer (HCC) is the fourth leading cause of cancer-related death globally and is most common in elderly patients with a peak incidence in the UK at ages 85–89 years. In addition to the well-established risk factors of alcohol and viral hepatitis B and C, rising obesity and associated non-alcoholic fatty liver disease is projected to contribute to increased incidence of advanced HCC in elderly patients. The management of advanced HCC is changing rapidly; for over a decade the multi-kinase inhibitor sorafenib has been the only treatment option that offered a proven survival advantage, but in the last 4 years other treatment options have emerged including other kinase inhibitors, and monoclonal antibodies targeting angiogenesis and immune checkpoint inhibitors. Recent clinical trials have recruited older patients with no maximum age exclusion criteria, and age has not been found to be predictive for treatment effect in subgroup analyses. Chronological age is an unreliable measure of fitness for treatment and frailty may be a more apt descriptor, but the lack of a unified assessment tool has limited its use in current practice. Development of unified frailty assessments and prospective large-scale studies of novel systemic therapies where age and frailty are evaluated would be informative. [ABSTRACT FROM AUTHOR]

The majority of patients diagnosed with cancer are ≥65 years. However, inclusion of older patients with cancer in clinical trials is limited, and so there is less evidence to guide systemic therapeutic decisions in these patients. There is also debate surrounding the definition of "older patients". Additionally, comorbidities, as well as life expectancy will influence compliance to any treatment, and physicians may favour less intense regimens for these patients or best supportive care alone. In patients with biliary tract cancer (BTC), surgery followed by adjuvant capecitabine (BILCAP phase 3 trial) is the only potentially curative option, but patients often present with advanced disease, and palliative systemic treatment is given. The availability of novel targeted therapies (oral and monotherapy) in selected populations of patients with BTC may increase the therapeutic artillery for these older patients. Trials to date in patients with BTC have not been age-specific and have not always included age subgroup analysis, and so the evidence to support treatment of older patients is derived via extrapolation, primarily, with only 35% being >60 years in the adjuvant BILCAP study, for example. When this evidence is provided, treated patients tend to gain equivalent survival benefit, irrespective of age. A comprehensive clinical geriatric assessment is recommended. Revision of existing BTC treatment guidelines should incorporate some reference to best practice in older patients with BTC. Observational data may also provide valuable insights in this population. Age sub-group analysis should be encouraged in prospective clinical trials including patients with BTC, with age-specific trials favoured. • Trials in BTC have not been age-specific nor always included age subgroup analysis. • Observational data may provide valuable insights in this population. • Retrospective evidence reports equivalent survival benefit, irrespective of age. • Comprehensive clinical geriatric assessments are recommended. • BTC therapy guidelines should reference best practice in older patients with BTC. [ABSTRACT FROM AUTHOR]

Pancreatic exocrine insufficiency (PEI) is highly prevalent in patients with pancreatic cancer, and has substantial implications for quality of life and survival. Post resection, PEI is associated with increased post-operative complications, longer hospital stays and higher costs. Treatment with pancreatic enzyme replacement therapy (PERT) improves quality of life and confers significant survival advantages. Despite this many patients with pancreatic cancer do not currently receive PERT. The nutritional consequences of PEI are extensive and even more relevant in the elderly owing to age related gastrointestinal tract and pancreatic changes that predispose to malnutrition. • PEI is prevalent in resectable and unresectable pancreatic cancer and is often undertreated; it is also progressive. • PEI symptoms are frequently mistakenly attributed to the underlying disease. • There is a strong evidence base for the use of PERT to improve nutritional parameters, quality of life and duration of survival. • Involvement of a dietician and continued nutritional and anthropometric assessments are essential to ensure nutritional optimisation. • Although not well explored, the reduction in pancreatic reserve in the elderly is likely to leave them at higher risk of PEI in pancreatic cancer and thus it is paramount that PEI must be considered early in this patient group and their nutritional status appropriately monitored. [ABSTRACT FROM AUTHOR]

Introduction: Since the beginning of the 2020 Sars-CoV-2 Italian outbreak, healthcare workers have been among the most exposed categories. There is little information about community pharmacists' on occupational exposure, symptoms development, and testing practices in the community pharmacist cohort.Methods: Between April 30th and May 10th, a questionnaire was administered through social media to Italian community pharmacists. From 67000 pharmacists currently working in community pharmacies, 1632 answered the survey.Results: The survey population reflected the general Italian community pharmacists population in terms of age, gender, and number of co-workers. Protective measures were adopted in up to 99.9% of pharmacies. 624 pharmacists (38.2%) developed at least one COVID-19 related symptom in the period between February 28th and May 10th. Also, 102 pharmacists (6.2%) were tested for COVID-19 and 15, the 15% of the tested population and 0.92% of the whole survey population, resulted positive on nasopharyngeal swab. However, while the number of symptomatic pharmacists decreased, a higher number of tests were performed, thus COVID-19 prevalence among community pharmacists could have been underestimated and is probably intermediate between other healthcare workers and the general population (0.31%).Conclusion: Community pharmacists have probably been one of the first categories to experience increased contact risk to SARS-CoV-2. COVID-19 prevalence among pharmacists could have been underestimated. In addition, the rates of protection measures adoption might have helped to reduce the spread of COVID-19 among co-workers and the community. [ABSTRACT FROM AUTHOR]

• Percutaneous dilatation tracheotomy enables non-surgeons to perform tracheotomies at patients bedside. • Bleeding is a common complication of percutaneous dilatation tracheotomies. • Performing a pre-operative neck ultrasound can help identifying aberrant vessels and reduce the risk of periprocedural bleeding. Percutaneous dilatation tracheotomy (PDT) is a relatively recent technique that enables non surgeons to perform tracheotomies at bedside reducing operation rooms schedules. It is burdened by a moderate risk of postoperative bleeding. The patient was a 57 years old with a temporal intraparenchymal hematoma, submitted to percutaneous dilatation tracheotomy. Despite the favorable anatomical features, a pre-procedural US was performed, identifying a pulsating vessel with an arterial pattern, 2 cm above the hollow. The procedure was then considered at high risk, an operation room was required for the technique and an on-call surgeon was alerted. The procedure was ended safely and any bleeding was avoided because the technique was practiced with the best precautions. PDT strength is the possibility for non surgeons to perform tracheotomies in selected patients at bedside, reducing operation rooms congestion. Such technique though is a "blind" technique, and postoperative bleedings can occur and represent a feared complication. Conversely, the surgical tracheotomy permits a better control of hemorrhages, but needs the involvement of a surgeon and availability of an operation room. Performing a PDT guided by a neck ultrasound is useful to identify eventual aberrant vessel whose course could complicate the tracheotomy, it is part of PDT guidelines of some States. US-PDT could help reducing procedure related complications selecting those high risk patients still in need of operating room and surgical assistance. US-PDT feasibility combined to its easy availability and low costs encourage its introduction into everyday practice. [ABSTRACT FROM AUTHOR]

Background and Aim: Increased intestinal permeability plays a key role in the pathogenesis of fat deposition in the liver. The aim of our study was to assess whether a single nucleotide polymorphism of protein tyrosine phosphatase non-receptor type 2 (PTPN2) (rs2542151 T→G), involved in intestinal permeability, may be associated with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM).Methods and Results: We recruited a prospective cohort of NAFLD subjects and matched controls. Clinical data, PTPN2 genotype and laboratory data were collected for each patient. Results were stratified according to liver histology and diabetes. We enrolled 566 cases and 377 controls. PTPN2 genotype distribution did not significantly differ between patients and controls. In the entire population, patients with PTPN2 rs2542151 T→G (dominant model) have a higher prevalence of diabetes; 345 patients (60.9%) underwent liver biopsy: 198 (57.4%) had steatohepatitis and 75 (21.7%) had advanced fibrosis. At multiple logistic regression analysis PTPN2 rs2542151 T→G was associated with T2DM (OR 2.14, 95% CI 1.04-4.40, P = 0.03). Patients who underwent liver biopsy, rs2542151 T→G of PTPN2 was independently associated with severe steatosis (OR 2.00, 95% CI 1.17-3.43, p = 0.01) and severe fibrosis (OR 2.23, 95% CI 1.06-4.72, P = 0.03).Conclusion: Our study shows that NAFLD patients with rs2542151 T→G of PTPN2 have a higher severity of fatty liver disease and a higher prevalence of T2DM. These results suggest that individual genetic susceptibility to intestinal permeability could play a role in liver disease progression. [ABSTRACT FROM AUTHOR]

• Evaluation of nine prothrombotic gene variants in 927 AMI patients compared to 430 healthy controls. • Only the genotype frequency of FVR2 and of the MTHFR C677T variants significantly differed between patients with AMI and the controls. • Only genotype frequencies of FVL, FII G20210A and MTHFR C677T variants significantly differed between patients with yAMI and the controls. • We found significative gender differences in the variants–disease association. [ABSTRACT FROM AUTHOR]

Older patients with cancer value functional outcomes as much as survival, but surgical studies lack functional recovery (FR) data. The value of a standardized frailty assessment has been confirmed, yet it's infrequently utilized due to time restrictions into everyday practice. The multicenter GOSAFE study was designed to (1) evaluate the trajectory of patients' quality of life (QoL) after cancer surgery (2) assess baseline frailty indicators in unselected patients (3) clarify the most relevant tools in predicting FR and clinical outcomes. This is a report of the study design and baseline patient evaluations. GOSAFE prospectively collected a baseline multidimensional evaluation before major elective surgery in patients (≥70 years) from 26 international units. Short−/mid−/long-term surgical outcomes were recorded with QoL and FR data. 1003 patients were enrolled in a 26-month span. Complete baseline data were available for 977(97.4%). Median age was 78 years (range 70–94); 52.8% males. 968(99%) lived at home, 51.6% without caregiver. 54.4% had ≥ 3 medications, 5.9% none. Patients were dependent (ADL < 5) in 7.9% of the cases. Frailty was either detected by G8 ≤ 14(68.4%), fTRST ≥ 2(37.4%), TUG > 20 s (5.2%) or ASAIII-IV (48.8%). Major comorbidities (CACI > 6) were detected in 36%; 20.9% of patients had cognitive impairment according to Mini-Cog. The GOSAFE showed that frailty is frequent in older patients undergoing cancer surgery. QoL and FR, for the first time, are going to be primary outcomes of a real-life observational study. The crucial role of frailty assessment is going to be addressed in the ability to predict postoperative outcomes and to correlate with QoL and FR. [ABSTRACT FROM AUTHOR]

Background Reprocessing of endoscopes is key to preventing cross-infection after colonoscopy. Culture-based methods are recommended for monitoring, but alternative and rapid approaches are needed to improve surveillance and reduce turnover times. A molecular strategy based on detection of residual traces from gut microbiota was developed and tested using a multicenter survey. Methods A simplified sampling and DNA extraction protocol using nylon-tipped flocked swabs was optimized. A multiplex real-time polymerase chain reaction (PCR) test was developed that targeted 6 bacteria genes that were amplified in 3 mixes. The method was validated by interlaboratory tests involving 5 reference laboratories. Colonoscopy devices (n = 111) were sampled in 10 Italian hospitals. Culture-based microbiology and metagenomic tests were performed to verify PCR data. Results The sampling method was easily applied in all 10 endoscopy units and the optimized DNA extraction and amplification protocol was successfully performed by all of the involved laboratories. This PCR-based method allowed identification of both contaminated (n = 59) and fully reprocessed endoscopes (n = 52) with high sensibility (98%) and specificity (98%), within 3-4 hours, in contrast to the 24-72 hours needed for a classic microbiology test. Results were confirmed by next-generation sequencing and classic microbiology. Conclusions A novel approach for monitoring reprocessing of colonoscopy devices was developed and successfully applied in a multicenter survey. The general principle of tracing biological fluids through microflora DNA amplification was successfully applied and may represent a promising approach for hospital hygiene. [ABSTRACT FROM AUTHOR]

Purpose: The extraction of a tooth is followed by hard and soft tissue changes that can compromise implant placement. The aim of the present retrospective study was to compare the clinical and radiographic outcomes of different ridge preservation procedures based on the use of leukocyte and platelet-rich fibrin (L-PRF).Materials and Methods: The study population consisted of all patients who had undergone surgery from January 1, 2017 to January 1, 2018 for alveolar ridge preservation on single posterior teeth using 3 clinical protocols: L-PRF alone, L-PRF mixed with a bone xenograft, and bone xenograft alone. Clinical and radiographic measures were recorded preoperatively and at 6 months postoperatively to determine the horizontal and vertical ridge resorption.Results: A total of 45 patients were included in the present study. All the surgeries were performed successfully, and no intraoperative complications developed. The L-PRF group experienced significantly greater horizontal and vertical bone resorption. The L-PRF plus bone xenograft group had less vertical and horizontal bone resorption than the bone xenograft alone group. Statistically significant differences in postoperative pain and wound healing were observed, with the bone xenograft alone group, in particular, having higher values for pain and experiencing delayed wound healing.Conclusions: Within the limitations of the present retrospective study, the use of a bone xenograft alone or L-PRF combined with a bone xenograft to perform alveolar ridge preservation procedures significantly limited bone resorption. [ABSTRACT FROM AUTHOR]

Information on disease-related malnutrition and related outcomes in pediatric patients with chronic diseases in different settings of care is not available. Consecutive eligible patients attending the out-patient clinic (n = 177) or admitted to the day-hospital clinic (n = 163) or to hospital (n = 201) were screened for the presence of malnutrition (BMI and/or height/length for age z-scores < –2). We recorded data on emergency care admissions to hospital that occurred during the 3 years before screening and related total days of stay, as well as data on emergency care admissions to hospital occurring within 6 months after screening. Prevalence of malnutrition was 2-fold higher (P < 0.001) in in-patients (56.7% [95% CI, 49.6–63.7]) than in patients assessed at the out-patient (33.3% [95% CI, 26.4–40.8]) and day-hospital (28.3% [95% CI, 21.5–35.8]) clinics. Estimates were heterogeneous across diagnostic groups with higher rates in patients with neurologic (61%) and cardiac (56%) diseases. Stunting was more frequent among in-patients, who also had more evident nutritional derangements. Multivariate logistic regression (covariates: age, gender, healthcare setting and disease group), showed that malnutrition (OR = 1.86 [95% CI, 1.21–2.88]; P = 0.005) was significantly associated with prolonged hospitalization (≥15 days) in the 3 years before screening. In-patients were also more likely to have been hospitalized ≥15 days (using out-patients as reference category, OR = 2.24 [95% CI, 1.39–3.63], P = 0.001), but we did not find any modifying effect (interaction) of the setting of care on the association between malnutrition and prolonged hospitalization. The rates of malnutrition in children with chronic diseases are very high and increase hospital care needs, especially when they are admitted to hospital. Nutritional care in this patient population is recommended. [ABSTRACT FROM AUTHOR]

• No ongoing nationwide registry exists in Latin America. • We describe the methodology behind RelevarEM, the first nationwide MS registry in Argentina and LATAM. • The structure, ethical aspects, implementation and variables of the registry are described. • RelevarEM has the objective of providing reliable real-world data of MS in Argentina and LATAM. Despite that different registries already exist in various countries in Europe and North America, no ongoing nationwide registry exists in Latin America (LATAM), a region where the disease behaves differently than in other regions. The objective of this document is to describe the methodology behind RelevarEM, the first nationwide MS registry in Argentina and LATAM. In this article, we described the creation, implementation and data management of the nationwide MS registry in Argentina. The registry contains information on the structure, ethical aspects, implementation and variables of the registry (Clinical Trials registry number NCT NCT03375177). RelevarEM is the first MS nationwide registry in Argentina, as well as in LATAM, with the objective of providing reliable real-world data of MS in the country. [ABSTRACT FROM AUTHOR]

Abstract Background This study sought to evaluate the impact of the advancements in clinical care, obtained over the last 20 years, for patients aged 70 and older undergoing liver resection for colorectal liver metastases (CRLM). Methods Consecutive patients age 70 or older who underwent liver resection for CRLM at Aintree University Hospital (Liverpool, UK) between May 2008 and May 2015 were compared to a dataset of consecutive patients, meeting the same criteria, between 1990 and 2007. An enhanced recovery programme after surgery (ERAS) combined with cardiopulmonary exercise testing (CPET) was introduced in January 2008. Results The proportion of patients over 70 years undergoing liver resection for CRLM increased over the study period (6% in 1990, 16.3% in 2000, 26.5% in 2005 and 25.8% in 2007). The patients in the later group were more often treated with neoadjuvant chemotherapy (58 vs 34, p = 0.006) and underwent parenchymal sparing surgery, resulting in fewer major hepatectomies (51 vs 111, p < 0.001) and less perioperative morbidity (49 vs 70, p = 0.043) and mortality (3 vs 9, p = 0.229). Although there was shorter disease free survival (DFS) in the later group (DFS at 1, 3 and 5 years was 52.1%, 31.6%, 29% vs. 71.8%, 49.1%, 44.0%)(p < 0.01), similar overall survival (OS) was achieved (OS at 1, 3 and 5 years was 85.4%, 51.6%, 32.8% vs. 81.7%, 42.1%, 27.3%)(p = 0.21). Conclusions This study demonstrates that, with modern management (ERAS, CPET, neoadjuvant chemotherapy and parenchymal sparing surgery), a greater number of patients with CRLM, over the age of seventy, can undergo liver resection, with improved perioperative outcomes. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is a complex disease, resulting from the interplay between environmental determinants and genetic variations. Single nucleotide polymorphism rs738409 C>G in the PNPLA3 gene is associated with hepatic fibrosis and with higher risk of developing hepatocellular carcinoma. Here, we analyzed a longitudinal cohort of biopsy-proven NAFLD subjects with the aim to identify individuals in whom genetics may have a stronger impact on disease progression. We retrospectively analyzed 756 consecutive, prospectively enrolled biopsy-proven NAFLD subjects from Italy, United Kingdom, and Spain who were followed for a median of 84 months (interquartile range, 65–109 months). We stratified the study cohort according to sex, body mass index (BMI) 2) and age (

Fibroscan is a well-established NIT for the diagnosis of advanced fibrosis (F>2) in patients with NAFLD, recently defined as compensated advanced chronic liver disease (cACLD). EASL Guidelines proposed 8 and 12 kPa, respectively, as rule-out and rule-in cut-offs for cACLD. Patients with Fibroscan measurement between 8 and 12 fall in a grey zone where further investigations are recommended. We recently proposed the cACLD Risk Score to further stratify this population. The main aim of this study was to test the diagnostic performance of the main NITs in a two European cohorts of patients with histological diagnosis of NAFLD. Secondly, we assessed the performance of the cACLD risk score to further stratify patients in the Fibroscan's grey zone. This is a retrospective observational study. We enrolled consecutive patients with histological diagnosis of NAFLD/NASH from January 2014 to December 2021 at two tertiary liver units in UK (the Royal Free Hospital, London - RFH) and Italy (Fondazione Universitaria Policlinico A. Gemelli IRCCS, Rome – FPG). We excluded patients who did not perform at least one of these NITs at time of biopsy (± 6 months): FIB4, NAFLD Fibrosis score (NFS), Fibroscan, APRI, AGILE3+, cACLD Risk Score. We performed a ROC analysis to explore the diagnostic performance of NITs for cACLD (F>2). Secondly, in patients with intermediate Fibroscan results (between 8-12 kPa), we tested the diagnostic performance of cACLD Risk Score. We included 536 patients;201 were female, median age was 53 years, and 44% had diabetes. Fibroscan and AGILE3+ score had the best diagnostic performances for cACLD with an AUROC of 0.81 and 0.83 respectively. (Fig. 1) EASL criteria showed a high sensitivity and high specificity for 8 kPa and 12 kPa cutoffs, respectively (Sens 84.3%; Spec 86.6%), wrong classification of 14.2% and 129 patients (24.1%) in the grey zone (between 8 and 12 kPa). Diagnostic performance of cACLD Risk Score in Fibroscan's grey zone was suboptimal (AUROC: 0.682). The use of Fibroscan+cACLD Risk Score vs Fibroscan alone showed a better overall accuracy (77.8% vs 61.7%) and a slight worsening of overall wrong classification rate (22.7% vs 14.2%) mainly due to a higher number of false negative than false positive. Among patients with intermediate Fibroscan (8-12 kPa), cACLD risk score correctly classify 64.4% of patients with a PPV of 72.0% and NPV of 62.5%. Our results suggest that cACLD Risk Score should be used in patients with indeterminate Fibroscan results in order to further stratify their risk of cACLD. The use of cACLD Risk Score improve the performance in identifying patients with cACLD (high PPV) although its false negative rate could lead to missed diagnosis (suboptimal NPV). Patients with intermediate fibroscan and low cACLD risk score should be still considered for further investigation (liver biopsy). [ABSTRACT FROM AUTHOR]

The post-neoadjuvant setting in early breast cancer represents an attractive scenario for adjuvant clinical trials, offering the opportunity to test new drugs or combinations in high-risk patients who did not achieve pathologic complete response after primary treatment. No standard therapies are routinely proposed to patients with residual disease after neoadjuvant chemotherapy and few trials have explored this setting. To date, only one randomized phase III study showed the benefit of additional capecitabine after neoadjuvant chemotherapy, and international guidelines recommend at least to consider its use, particularly for triple negative breast cancer. Therefore, the management of these patients is still a clinical challenge, with limited data supporting the use of an additional adjuvant non-cross-resistant chemotherapy. Escalation strategies are currently under evaluation, with new agents proposed as supplementary post-neoadjuvant treatment (e.g. platinum salts, capecitabine, poly ADP-ribose polymerase inhibitors, immune checkpoint inhibitors, cyclin-dependent kinase 4/6 inhibitors). Based on these premises, selection criteria are critical to identify patients who may benefit from post-neoadjuvant therapies, through the validation of prognostic and predictive biomarkers for a reliable risk assessment and estimation of benefit. The present review summarizes the efforts in introducing new therapeutic options for patients with breast cancer and residual disease after neoadjuvant treatment, with a particular focus on the ongoing clinical trials and useful biomarkers for risk stratification. [ABSTRACT FROM AUTHOR]

Abstract With an expanding elderly population and median rectal cancer detection age of 70 years, the prevalence of rectal cancer in elderly patients is increasing. Management is based on evidence from younger patients, resulting in substandard treatments and poor outcomes. Modern management of rectal cancer in the elderly demands patient-centered treatment, assessing frailty rather than chronological age. The heterogeneity of this group, combined with the limited available data, impedes drafting evidence-based guidelines. Therefore, a multidisciplinary task force convened experts from the European Society of Surgical Oncology, European Society of Coloproctology, International Society of Geriatric Oncology and the American College Surgeons Commission on Cancer, with the goal of identifying the best practice to promote personalized rectal cancer care in older patients. A crucial element for personalized care was recognized as the routine screening for frailty and geriatrician involvement and personalized care for frail patients. Careful patient selection and improved surgical and perioperative techniques are responsible for a substantial improvement in rectal cancer outcomes. Therefore, properly selected patients should be considered for surgical resection. Local excision can be utilized when balancing oncologic outcomes, frailty and life expectancy. Watch and wait protocols, in expert hands, are valuable for selected patients and adjuncts can be added to improve complete response rates. Functional recovery and patient-reported outcomes are as important as oncologic-specific outcomes in this age group. The above recommendations and others were made based on the best-available evidence to guide the personalized treatment of elderly patients with rectal cancer. [ABSTRACT FROM AUTHOR]

Abstract Background The incidence of pancreatic ductal adenocarcinoma (PDAC) is rapidly increasing. Up to 30% of patients present with locally advanced disease and therefore are not candidates for surgery. Locally advanced pancreatic cancer (LAPC) is an emerging entity lacking in level III evidence-based recommendations for its treatment. Currently, systemic chemotherapy is the main treatment for LAPC. However, due to lack of response or disease progression, downsizing of the tumour, making it resectable is successful in only a small proportion of patients. Radiotherapy is often advocated to improve local disease control if there is stability following chemotherapy. Recently, Irreversible Electroporation (IRE), a novel non-thermal ablation technique, has been proposed for the treatment of LAPC. Aims and methods This narrative review aims to explore the potential role and timing for the use of IRE in patients with LAPC. Results To date, there is limited and inconsistent level I and II evidence available in the literature regarding the use of IRE for the treatment of PDAC. Discussion Although some of the preliminary experience of the use of IRE in patients with LAPC is encouraging, it should only be used after conventional evidence-based treatments and/or within the research context. [ABSTRACT FROM AUTHOR]

Introduction The purpose of this study was to assess the impact of access cavity preparation and the remaining tooth substance on the fracture strength of endodontically treated teeth. Methods One hundred sound mandibular first and second molar teeth were selected and divided into 1 control and 9 test groups ( n = 10/group) as follows: control group, intact teeth; group 1, teeth prepared with traditional endodontic access cavity (TEC); group 2, teeth prepared with conservative endodontic access cavity (CEC); group 3, teeth prepared with truss endodontic access cavity (TREC); group 4, TEC + 3 residual walls; group 5, CEC + 3 residual walls; group 6, TREC + 3 residual walls; group 7, TEC + 2 residual walls; group 8, CEC + 2 residual walls; and group 9, TREC + 2 residual walls. After access cavity preparation, all test teeth were endodontically treated and restored. The specimens were then loaded to fracture in a universal loading machine (Triaxial Tester T400 Digital; Controls srl, Cernusco, Italy), and fracture values were recorded in newtons. The data were analyzed with 2-way analysis of variance and Tukey post hoc analysis for multiple comparisons ( P < .05). Results Intact teeth were more resistant to fracture than the teeth in all the test groups. No statistically significant differences were found between the 3 tested access cavities ( P > .05). Significant differences were observed between the different number of residual walls ( P < .05). Conclusions TRECs do not increase the fracture strength of endodontically treated teeth in comparison with CECs and TECs. Moreover, the loss of mesial and distal ridges reduced the fracture strength of teeth significantly. [ABSTRACT FROM AUTHOR]

Non-specific gastrointestinal symptoms, including pain, diarrhoea, nausea, and vomiting, can be the first symptoms of Fabry disease. They may suggest more common disorders, e.g. irritable bowel syndrome or inflammatory bowel disease. The confounding clinical presentation and rarity of Fabry disease often cause long diagnostic delays and multiple misdiagnoses. Therefore, specialists involved in the clinical evaluation of non-specific upper and lower gastrointestinal symptoms should recognize Fabry disease as a possible cause of the symptoms, and should consider Fabry disease as a possible differential diagnosis. When symptoms or family history suggest Fabry disease, in men, low alpha-galactosidase A enzyme levels, and in women, specific Fabry mutations confirm the diagnosis. In addition to symptomatic treatments, disease-specific enzyme replacement therapy with recombinant human alpha-galactosidase A enzyme or chaperone therapy (migalastat) in patients with amenable mutations can improve the disease, including gastrointestinal symptoms, and should be initiated as early as possible after Fabry disease has been confirmed; starting enzyme replacement therapy at as young an age as possible after diagnosis improves long-term clinical outcomes. Improved diagnostic tools, such as a modified gastrointestinal symptom rating scale, may facilitate diagnosing Fabry disease in patients with gastrointestinal symptoms of unknown cause and thus assure timely initiation of disease-specific treatment. [ABSTRACT FROM AUTHOR]

Microsurgical revascularization stands as the preferred method for addressing erectile dysfunction (ED) resulting from traumatic penile arterial insufficiency. Traditional microarterial bypass surgery (MABS) techniques have typically relied on utilizing the inferior epigastric artery (IEA) as the graft vessel. However, issues such as endothelial dysfunction in the vessel and alterations in abdominal tissue can negatively impact surgical outcomes. MABS using the descending branch of the lateral circumflex artery of the femur (DLCFA) should be proposed as a surgical option for penile arterial revascularization. A 29-year-old who experienced ED after a pelvic bone fracture with hypogastric vascular injury was referred to our center. Preoperatory penile Doppler ultrasound (PDU) examination documented the presence of arterial insufficiency. Selective hypogastric angiography pointed out the interruption of arterial blood flow at the level of the distal right internal pudendal artery. Access to the dorsal penile artery was gained through an infrapubic incision, the DLCFA pedicle was isolated through an incision along the anterolateral right thigh. After its transposition, the arterial bundle was anastomosed to the dorsal penile artery in an end-to-end fashion. Intraoperative PDU has been used to verify the patency of the anastomosis. At 6 months follow-up, optimal flow parameters on PDU were persistently registered, and the patient had consistent clinical improvement on the IIEF-5 score. DLCFA grafting for penile revascularization is a suitable therapeutic option in traumatic ED due to its size and accessibility. Further experience is necessary to compare clinical outcomes among different revascularization techniques. • In the event of a traumatic interruption of arterial flow, penile microsurgical revascularization is considered the treatment of choice for the correction of Erectile Dysfunction (ED); • The proposed surgical techniques up to now involve the isolation of the Inferior Epigastric Artery (IEA) and its transposition to the pudendal or penile arterial vessels; • The harvesting of the IEA may become a challenging procedure, as well as the patency of the blood vessel could be compromised by atherosclerotic plaques; • The Descending Branch of the Lateral Circumflex Femoral Artery has the potential to be a valid alternative as a graft vessel for the end-to-end anastomosis to the distal stump of the dorsal penile artery; • The presented case provides a detailed description of the innovative surgical procedure in the andrological field and confirms the positive outcomes of the microsurgical revascularization techniques. [ABSTRACT FROM AUTHOR]

• There are limited data regarding the use of high-efficacy treatments in LATAM. • One third of those patients received HETs as the first treatment, in second epoch analyzed. • Significant increase in the use of HETs was observed last years. • The most frequently used HETs were cladribine between 2018 and 2020. Disease-modifying therapies (DMTs) in multiple sclerosis (MS) can be classified according to the efficacy in which they prevent inflammatory activity. To date, there are limited data regarding the use of high-efficacy treatments (HETs) in Latin America (LATAM). We aimed to analyze the use of HETs in Argentina, focusing on the clinical and sociodemographic characteristics of the patients who use these treatments and the changes in the trend of use over the years. A retrospective cohort study was done using the Argentina MS patient registry, RelevarEM. Patients diagnosed with relapsing-remitting MS (RRMS) according to validated diagnostic criteria and under treatment with natalizumab, alemtuzumab, cladribine, rituximab or ocrelizumab were included. Out of 2450 RRMS patients under a DMT, 462 (19%) were on HETs. One third of those patients (35%) received HETs as the first treatment. The most frequent reason for switching to HETs was treatment failure to previous DMT (77%). The time from MS diagnosis to the first HET in treatment-naive patients was less than one year (IQR: 0–1 year) and in treatment-experienced patients it was 5 years (IQR: 3–9 years). Between 2015 and 2017 (P1), 729 patients included in RelevarEM started a new treatment, of which 85 (11.65%) were HETs. Between 2018 and 2020 (P2), 961 patients included in RelevarEM started a new treatment, of which 284 (29.55%) were HETs. When comparing P2 with P1, a significant increase in the use of HETs was observed (p < 0.01). The most frequently used HETs were alemtuzumab (50.59%) in P1, and cladribine (45.20%) in P2. The demographic and clinical characteristics of patients under HET in Argentina were identified. Based on a real-world setting, we found a significant trend towards and a rapid increase in the use of HETs in clinical practice in patients with RRMS. [ABSTRACT FROM AUTHOR]

Buildings exposed to high-intensity flood actions can experience severe damage and collapse. Rapid procedures can significantly aid in identifying the most vulnerable buildings within large flood-risk areas, enabling the implementation of retrofitting and mitigation measures. Motivated by this need, in this work we propose a simplified vulnerability assessment method that employs a mechanics-based approach. This strategy exclusively addresses the structural damage and is based on assigning a Vulnerability Index to each building. Then, considering some hazard intensity indicators, the method gives the most probable damage level. The main novelty of the proposed method lies in its calibration, which is performed on the results of a high number of numerical analyses. Results show a good agreement between the proposed simplified method and the numerical simulations, particularly in estimating high or low damage levels. Finally, the method is applied to a case study regarding the municipality of Crotone, in southern Italy. [ABSTRACT FROM AUTHOR]