To Be Frail or Not to Be Frail: This Is the Question-A Critical Narrative Review of Frailty.

Many factors have contributed to rendering frailty an emerging, relevant, and very popular concept. First, many pandemics that have affected humanity in history, including COVID-19, most recently, have had more severe effects on frail people compared to non-frail ones. Second, the increase in human life expectancy observed in many developed countries, including Italy has led to a rise in the percentage of the older population that is more likely to be frail, which is why frailty is much a more common concern among geriatricians compared to other the various health-care professionals. Third, the stratification of people according to the occurrence and the degree of frailty allows healthcare decision makers to adequately plan for the allocation of available human professional and economic resources. Since frailty is considered to be fully preventable, there are relevant consequences in terms of potential benefits both in terms of the clinical outcome and healthcare costs. Frailty is becoming a popular, pervasive, and almost omnipresent concept in many different contexts, including clinical medicine, physical health, lifestyle behavior, mental health, health policy, and socio-economic planning sciences. The emergence of the new "science of frailty" has been recently acknowledged. However, there is still debate on the exact definition of frailty, the pathogenic mechanisms involved, the most appropriate method to assess frailty, and consequently, who should be considered frail. This narrative review aims to analyze frailty from many different aspects and points of view, with a special focus on the proposed pathogenic mechanisms, the various factors that have been considered in the assessment of frailty, and the emerging role of biomarkers in the early recognition of frailty, particularly on the role of mitochondria. According to the extensive literature on this topic, it is clear that frailty is a very complex syndrome, involving many different domains and affecting multiple physiological systems. Therefore, its management should be directed towards a comprehensive and multifaceted holistic approach and a personalized intervention strategy to slow down its progression or even to completely reverse the course of this condition.

Nonthyroidal Illness Syndrome: To Treat or Not to Treat? Have We Answered the Question? A Review of Metanalyses.

Background and Objective: Nonthyroidal Illness Syndrome (NTIS) occurs in approximately 70% of patients admitted to Intensive Care Units (ICU)s and has been associated with increased risk of death. Whether patients with NTIS should receive treatment with thyroid hormones (TH)s is still debated. Since many interventional randomized clinical trials (IRCT)s were not conclusive, current guidelines do not recommend treatment for these patients. In this review, we analyze the reasons why TH treatment did not furnish convincing results regarding possible beneficial effects in reported IRCTs. Methods: We performed a review of the metanalyses focused on NTIS in critically ill patients. After a careful selection, we extracted data from four metanalyses, performed in different clinical conditions and diseases. In particular, we analyzed the type of TH supplementation, the route of administration, the dosages and duration of treatment and the outcomes chosen to evaluate the results. Results: We observed a marked heterogeneity among the IRCTs, in terms of type of TH supplementation, route of administration, dosages and duration of treatment. We also found great variability in the primary outcomes, such as prevention of neurological alterations, reduction of oxygen requirements, restoration of endocrinological and clinical parameters and reduction of mortality. Conclusions: NTIS is a frequent finding in critical ill patients. Despite several available IRCTs, it is still unclear whether NTIS should be treated or not. New primary endpoints should be identified to adequately validate the efficacy of TH treatment and to obtain a clear answer to the question raised some years ago.

Potential markers of healing from near infrared spectroscopy imaging of venous leg ulcer. A randomized controlled clinical trial comparing conventional with hyperbaric oxygen treatment.

The aim of this study is to ascertain whether the simultaneous measurement of hemoglobin O2 saturation (StO2 ) and dimension of venous leg ulcers (VLU) by near infrared spectroscopy (NIRS) imaging can predict the healing course with protocols employing a conventional treatment alone or in combination with hyperbaric oxygen therapy (HBOT). NIRS 2D images of wound region were obtained in 81 patients with hard-to-heal VLU that had been assigned, in a randomized controlled clinical trial, to the following protocols: 30 HBOT sessions, adjunctive to the conventional therapy, either twice daily over 3 weeks (group A) or once daily over 6 weeks (group B), and conventional therapy without HBOT (group C). Seventy-three patients completed the study with a total of 511 NIRS images being analyzed. At the end of treatment, wound area was significantly smaller in all three groups. However, at the 3-week mark the wound area reduction tended to be less evident in group A than in the other groups. This trend continued up to the 6-week end-point when a significantly greater area reduction was found with group B (65.5%) and group C (56.8%) compared to group A (29.7%) (P < .01). Furthermore, a higher incidence of complete healing was noted with group B (20%) than with group A (4.5%) and group C (3.8%). When using a final wound reduction in excess of 40% to distinguish healing from nonhealing ulcers, it was found that only the former present NIRS StO2 values abating over the study period both at center and edge of lesions. In conclusion, NIRS analysis of StO2 and wound area can predict the healing course of VLU. Adjunctive HBOT significantly facilitates VLU healing compared to the conventional treatment alone. This positive action, however, becomes manifest only with a longer and less intensive treatment schedule.

Computational Prediction of Potential Inhibitors of the Main Protease of SARS-CoV-2.

The rapidly developing pandemic, known as coronavirus disease 2019 (COVID-19) and caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently spread across 213 countries and territories. This pandemic is a dire public health threat-particularly for those suffering from hypertension, cardiovascular diseases, pulmonary diseases, or diabetes; without approved treatments, it is likely to persist or recur. To facilitate the rapid discovery of inhibitors with clinical potential, we have applied ligand- and structure-based computational approaches to develop a virtual screening methodology that allows us to predict potential inhibitors. In this work, virtual screening was performed against two natural products databases, Super Natural II and Traditional Chinese Medicine. Additionally, we have used an integrated drug repurposing approach to computationally identify potential inhibitors of the main protease of SARS-CoV-2 in databases of drugs (both approved and withdrawn). Roughly 360,000 compounds were screened using various molecular fingerprints and molecular docking methods; of these, 80 docked compounds were evaluated in detail, and the 12 best hits from four datasets were further inspected via molecular dynamics simulations. Finally, toxicity and cytochrome inhibition profiles were computationally analyzed for the selected candidate compounds.

Hypnosis-Aided Awake Surgery for the Management of Intrinsic Brain Tumors versus Standard Awake-Asleep-Awake Protocol: A Preliminary, Promising Experience.

BACKGROUND: Hypnosis is a technique that could aid awake surgery protocols. The aim of the present study is to describe the results of a preliminary experience of a cohort of patients operated on with an original protocol of hypnosis-aided awake surgery (HAS). METHODS: All patients were operated on with the aid of HAS and their data were retrospectively reviewed. A thorough literature review was conducted to compare the results of HAS with the standard awake surgery protocol regarding 1) the incidence of intraoperative pain; 2) the overall incidence of complications; 3) the length of time in which the patients were suitable for intraoperative neuropsychological testing; and 4) the incidence of gross total resection. The comparison presented a notably high statistical impact (1-ß = 0.90-0.93 for α = 0.05; effect size, 0.5). RESULTS: The final cohort comprised 6 patients from our institution and 43 records retrieved in the relevant literature underwent HAS for intrinsic brain tumor treatment. This cohort was compared with cohorts of patients who were considered eligible through a literature review. HAS showed a statistically significant superiority in the first 3 outcome variables, whereas the incidence of gross total resection favored the standard awake approaches. CONCLUSIONS: According to the results, hypnosis-aided resection of intrinsic brain tumor located in eloquent areas is safe and effective, although dissociation phenomena deserve further investigation to be completely understood.

Hyperbaric oxygen therapy with short duration intratympanic steroid therapy for sudden hearing loss.

CONCLUSION: The excellent tolerability of intratympanic (IT) steroid offers the possibility to use a high dose, which would appear to be more effective than intravenous (IV) steroid treatment, when both are associated with hyperbaric oxygen (HBO) therapy. OBJECTIVE: The purpose of the study was to assess for the first time the efficacy of the association of IT steroid and HBO therapy in patients presenting idiopathic sudden sensorineural hearing loss (ISSNHL), comparing this protocol with another consisting of IV steroid administration and HBO therapy. METHODS: A total of 48 patients presenting ISSNHL were recruited. Patients were divided into two categories: the severe ISSNHL group with a pure-tone average (PTA) between 70 and 90 dB, and the profound ISSNHL group with a PTA >90 dB. The first protocol consisted of 10 days of HBO therapy together with IV methylprednisolone 1 mg/kg body weight for 7 days; the second protocol consisted of HBO therapy for 10 days, associated with an IT injection of prednisolone at a dose of 62.5 mg/ml, once a day for 3 consecutive days, performed 2 h before the HBO therapy. RESULTS: The overall success rate was superior in the group submitted to IT steroid and HBO therapy. Nevertheless, these clinical results were not statistically significant.

Cytoreductive surgery (peritonectomy procedures) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of diffuse peritoneal carcinomatosis from ovarian cancer.

BACKGROUND: Because of scarce data from larger series and nonhomogeneous selection criteria, further information is needed on peritonectomy with hyperthermic intraperitoneal chemotherapy (HIPEC) in managing patients with ovarian peritoneal carcinomatosis. METHODS: In an open, prospective, single-center nonrandomized phase 2 study conducted from November 2000 to April 2007, 47 patients with primary advanced or recurrent ovarian cancer and diffuse peritoneal carcinomatosis were enrolled; 22 underwent primary and 25 secondary cytoreduction plus immediate HIPEC followed by systemic chemotherapy. RESULTS: The overall mean Sugarbaker peritoneal cancer index was 14.9 (range, 6-28). A mean of 6 surgical procedures were required per patient (range, 4-10). In 87.3% of the patients debulking achieved optimal cytoreduction (Sugarbaker completeness of cytoreduction [CC] score 0-1), whereas in 12.7% it left macroscopic residual disease (CC-2 or CC-3). Major complications developed in 21.3% of the patients and the in-hospital mortality rate was 4.2%. The mean overall survival was 30.4 months, median survival was 24 months, and mean disease-free survival was 27.4 months. Five-year survival was 16.7%. Univariate (log-rank test and analysis of variance) and multivariate analyses (Cox proportional-hazard model) identified the CC score as the main factor capable of independently influencing survival. CONCLUSIONS: Peritonectomy procedures combined with HIPEC offer promising long-term survival in patients with diffuse peritoneal ovarian carcinomatosis. They achieve high adequate primary and secondary surgical cytoreduction rates with acceptable morbidity and mortality.

Slowing the degenerative process, long lasting effect of hyperbaric oxygen therapy in retinitis pigmentosa.

BACKGROUND: Retinitis pigmentosa (RP) therapy is still an unsolved challenge. Recent reports have underlined that hyperbaric oxygen (HBO) therapy could play a role in slowing the retinal degenerative process. The aim of this study was to assess the efficacy of HBO therapy on visual function in RP patients. METHODS: We performed a single-center, comparative, longitudinal case-controlled randomized clinical trial, which lasted 10 years. We randomly divided RP patients into two groups. Group 1, the control group, consisted of 44 RP patients (21 males and 23 females; mean age 35.5) who took Vitamin A. Group 2, with 44 RP patients (21 males and 23 females; mean age 35,02), underwent HBO therapy. No statistically significant difference was found at the beginning of the study between the two groups. We compared the results concerning visual acuity, Goldmann perimetry, static perimetry Humphrey field analyzer (HFA), and electroretinogram (ERG) obtained in the two groups at 5 and 10 years follow-up. Statistical analysis was performed with Kaplan-Meier life-table with the evaluation of log-rank coefficient. RESULTS: At 5 year follow-up, 87.5% of group 2 patients preserved 80% of the initial visual acuity, while the same result was achieved in only 70.4% of group 1 patients (X(2) = 8.2; p < 0.01); at 10 year follow-up, 63.33% of group 2 patients preserved 80% of the initial visual acuity, while the same percentage of residual visual acuity was maintained in 40% of group 1 patients (X(2) = 3.22; p = 0.05). At 10 year follow-up, Goldmann perimetry (target I4e) did not change in 31.6% of group 2 and in 10.5% of group 1; evaluation of mean defect (MD) with static perimetry HFA showed that 53% of HBO patients had 80% of residual mean sensitivity compared to 23.5% of the control group patients (X(2) = 4.72; p = 0.035). ERG b-wave mean values at the end of the protocol were significantly higher in the HBO treated group (X(2) = 4.53; p = 0.013). CONCLUSION: Our study underlines that HBO therapy can be a safe alternative approach to RP patients, contributing to the stabilization of their visual function concerning visual acuity, visual field, and ERG responses while waiting for a definite cure.