Medicina, Volume 57, Issue 1 (January 2021) – 81 articles

The COVID-19 pandemic has led to a reduction in hip and knee replacement surgery across healthcare systems. When regular operating returns, there will be a large volume of patients and an emphasis on a short hospital stay. Patients will be keen to return home, and capacity will need to maximised. Strategies to reduce the associated risks of surgery and to accelerate recovery will be needed, and so Enhanced Recovery after Surgery (ERAS) should be promoted as the model of care. ERAS protocols are proven to reduce hospital stay safely; however, ERAS pathways may require adaption to ensure both patient and staff safety. The risk of exposure to possible sources of COVID-19 should be limited, and so hospital visits should be minimised. The use of technology such as smartphone apps to provide pre-operative education, wearable activity trackers to assist with rehabilitation, and the use of telemedicine to complete outpatient appointments may be utilised. Also, units should be reminded that ERAS protocols are multi-modal, and every component is vital to minimise the surgical stress response. The focus should be on providing better and not just faster care. Units should learn from the past in order to expedite the implementation of or adaption of existing ERAS protocols. Strong leadership will be required, along with a supportive organisational culture, an inter-professional approach, and a recognised QI method should be used to contextualize improvement efforts. Full article

Background and Objectives: There is general agreement on the benefits of laparoscopy for treatment of rectal and left colon cancers, whereas findings regarding the comparison of laparoscopic and open right colonic resections are discordant. The aim of this systematic review and meta-analysis was to assess the outcomes and advantages of laparoscopic versus transverse-incision open surgery for management of right colon cancer. Materials and Methods: A systematic review was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Comparative studies evaluating the results of laparoscopic and transverse-incision open right hemicolectomies were analyzed. The measured outcomes were mean operative time, time to feeding, duration of hospital stay, and number of lymph nodes harvested. Results: A total of 5 studies including 318 patients met the inclusion criteria. Meta-analysis revealed no differences in time to resume oral feeding, hospital stay, and number of lymph nodes harvested in between groups, but mean length of surgery was significantly longer in the laparoscopic group. Conclusion: These data confirm that the preferred approach to right hemicolectomy is yet unclear. Laparoscopy has a longer operative time than transverse-incision open surgery, and no significant short-term benefits were observed for the studied parameters. Well-designed randomized control trials (RCTs) might help to identify the differences between these two techniques for the surgical treatment of right colon cancer. Full article

Background and Objectives: Sugammadex is a modified γ-cyclodextrin largely used to prevent postoperative residual neuromuscular blockade induced by neuromuscular aminosteroid blocking agents. Although Sugammadex is considered more efficacious and safer than other drugs, such as Neostigmine, significant and serious complications after its administration, such as hypersensitivity, anaphylaxis and, more recently, severe cardiac events, are reported. Case presentation: In this report, we describe the case of an 80-year-old male with no medical history of cardiovascular disease who was scheduled for percutaneous nephrolithotripsy under general anesthesia. The intraoperative course was uneventful; however, the patient developed a rapid and severe hypotension, asystole and cardiac arrest after Sugammadex administration. Spontaneous cardiac activity and hemodynamic stability was restored with pharmacological therapy and chest compression. The patient was stabilized and discharged uneventfully on postoperative day 10. Conclusions: The potential causes of cardiac arrest after Sugammadex administration have been carefully considered, yet all indications point to Sugammadex as the direct causative agent. On the basis of laboratory and clinical tests, we can exclude among the cause of bradycardia, Kounis syndrome, acute myocardial infarction, coronary spasm and other arrhythmias, but not anaphylaxis. Although Sugammadex is considered an increasingly important option in the prevention of postoperative residual neuromuscular blockade, anesthesiologists should consider it a causative agent of cardiac arrest during surgery. This case highlights the necessity of increased pharmacovigilance and further studies to examine Sugammadex safety and mechanism through which it may cause severe bradycardia, hypotension and cardiac arrest. Full article

Background and Objectives: Aortic valve stenosis (AS) develops with a pronounced local inflammatory response, where a variety of growth factors are involved in the process, and may have a pro-inflammatory and anti-inflammatory effect. The aim of our study was to elucidate whether circulating growth factors: growth differentiation factor 15 (GDF-15), angiopoietin-2 (Ang-2), vascular endothelial growth factor A (VEGF-A), fibroblast growth factor 2 (FGF-2), and fibroblast growth factor 21 (FGF-21) could be proposed as clinically relevant biomarkers to improve risk stratification in AS patients. Materials and Methods: AS patients were classified into three groups: 16 patients with mild AS stenosis; 19 with moderate and 11 with severe AS, and 30 subjects without AS (echocardiographically approved) were selected as a control group. GDF-15, Ang-2, VEGF-A, FGF-2, and FGF-21 were measured in plasma by the ELISA method. Results: GDF-15 levels differed significantly not only when comparing AS patients with control groups (p < 0.0001), but also a statistically significant difference was achieved when comparing AS patients at a mild degree stage with control individuals. We found a strong relationship of GDF-15 levels regarding AS severity degree (p < 0.0001). VEGF-A, FGF-2 and FGF-21 levels were significantly higher in AS patients than in controls, but relationships regarding the AS severity degree were weaker (p < 0.02). ROC analysis of the study growth factors showed that GDF-15 might serve as a specific and sensitive biomarker of AS stenosis (AUC = 0.75, p = 0.0002). FGF-21 correlated with GDF-15, Ang-2, and FGF-2, but it did not reach the level to serve as a clinically relevant biomarker of AS stenosis. Conclusions: AS is associated with significantly increased GDF-15, VEGF-A, FGF-2, and FGF-21 levels in plasma, but only GDF-15 shows a pronounced relationship regarding AS severity degree, and GDF-15 might serve as a specific and sensitive biomarker of AS stenosis. Full article

Background and Objectives: An increasing number of patients (pts) with locally advanced pancreatic cancer (LAPC) are treated with an intensive neoadjuvant therapy to obtain a secondary curative resection. Only a certain number of patients benefit from this intention. The aim of this investigation was to identify prognostic factors which may predict a benefit for secondary resection. Materials and Methods: Survival time and clinicopathological data of pts with pancreatic cancer were prospective and consecutively collected in our Comprehensive Cancer Center Database. For this investigation, we screened for pts with primarily unresectable pancreatic cancer who underwent a secondary resection after receiving induction therapy in the time between March 2017 and May 2019. Results: 40 pts had a sufficient database to carry out a reliable analysis. The carbohydrate-antigen 19-9 (CA 19-9) level of the pts treated with induction therapy decreased by 44.7% from 4358.3 U/mL to 138.5 U/mL (p = 0.001). The local cancer extension was significantly reduced (p < 0.001), and the Eastern Cooperative Oncology Group (ECOG) performance status was lowered (p = 0.03). The median overall survival (mOS) was 20 months (95% CI: 17.2–22.9). Pts who showed a normal CA 19-9 level (<37 U/mL) at diagnosis and after neoadjuvant therapy or had a Body Mass Index (BMI) below 25 kg/m² after chemotherapy had a significant prolonged overall survival (29 vs. 19 months, p = 0.02; 26 vs. 18 months, p = 0.04; 15 vs. 24 months, p = 0.01). Pts who still presented elevated CA 19-9 levels >400 U/mL after induction therapy did not profit from a secondary resection (24 vs. 7 months, p < 0.001). Nodal negativity as well as the performance of an adjuvant therapy lead to better mOS (25 vs. 15 months, p = 0.003; 10 vs. 25 months, p < 0.001). Conclusion: The pts in our investigation had different benefits from the multimodal treatment. We identified the CA 19-9 level at time of diagnosis and after neoadjuvant therapy as well as the preoperative BMI as predictive factors for overall survival. Furthermore, diagnostics of presurgical nodal status should gain more importance as nodal negativity is associated with better outcome. Full article

Fish allergy constitutes a severe problem worldwide. Its prevalence has been calculated as high as 7% in paediatric populations, and in many cases, it persists into adulthood with life-threatening signs and symptoms. The following review focuses on the epidemiology of Immunoglobulin E (IgE)-mediated fish allergy, its pathogenesis, clinical manifestations, and a thorough approach to diagnosis and management in the paediatric population. The traditional approach for managing fish allergy is avoidance and rescue medication for accidental exposures. Food avoidance poses many obstacles and is not easily maintained. In the specific case of fish, food is also not the only source of allergens; aerosolisation of fish proteins when cooking is a common source of highly allergenic parvalbumin, and elimination diets cannot prevent these contacts. Novel management approaches based on immunomodulation are a promising strategy for the future of these patients. Full article

Background and Objective: The routine practice of self-medication of blood pressure (BP) not oriented with pulse devices may not be precisely useful in the control of BP and can lead the patient to self-medicate in error. Thus, we need to evaluate the non-oriented self-assessment of BP in real-life circumstances in hypertensive patients. The objective of this study was to evaluate in hypertensive patients the association of BP self-measurement with its control, as well as the presence of anxiety disorders, the occurrence of unscheduled visits to the emergency room, and self-medication. Materials and Methods: An observational study was carried out with 1000 hypertensive volunteers (age: 61.0 ± 12.5). Using a questionnaire, sociodemographic and clinical data on BP control were collected. Anxiety was assessed by the State-Trait Anxiety Inventory (STAI). Results: The group that performed non-oriented self-measurement of BP, showed that they had higher frequencies of self-medication (57.9%, p < 0.05) and more unscheduled visits to the emergency room (68%, p < 0.05). In addition, a lower level of BP control (46.8%, p < 0.05) was associated with higher levels of anxiety (52.3%, p < 0.05) in the group that performed non-oriented self-measurements of BP. Conclusion: The practice of non-oriented self-assessment of BP was associated with negative factors such as high levels of anxiety and higher frequencies of self-medication and unscheduled emergency visits. Full article

Background and Objectives: Different arthroscopic procedures are used for partial-thickness rotator cuff tears (PT-RCTs), but there is still no evidence on the superiority of one procedure over the other. The aim of this study was to evaluate the clinical outcomes and the rate of complications of a tear completion repair (TCR) technique. Materials and Methods: Patients who had undergone arthroscopic TCR technique for PT-RCTs with a follow-up of at least 2-years after surgery were included. The TCR technique involved the removal of the “critical zone” and creating microfractures to biologically support tendon healing. Functional outcomes were assessed prospectively by the Constant score (CS) and active and passive range of movement (ROM). Pain and patient satisfaction were measured using a visual analog scale (VAS). Complication rates were recorded, and tendon integrity was assessed with magnetic resonance imaging (MRI) or ultrasound performed at least 2-years after surgery. Results: Eighty-seven patients with a median age of 57 years were followed-up for a median of 5 years. The CS score improved from 53.5 preoperatively to 94.0 postoperatively (p < 0.001). Median VAS score decreased from 8.6 to 1.0 (p < 0.0001). Median patient satisfaction was 9.3. The overall complication rate was 14.9%. Conclusions: Patients with PT-RCTs of the supraspinatus tendon treated by the TCR technique with “critical zone” removal and biological stimulation by microfractures showed good functional results with excellent strength recovery, a high degree of patient satisfaction, and resolution of painful symptoms at mid-term follow-up. Full article

Pathology of the lumbar spine and hip joint can commonly coexist in the elderly. Anterior and lateral leg pain as symptoms of hip osteoarthritis and spinal stenosis can closely resemble each other, with only subtle differences in both history and physical examinations. It is not easy to identify the origin of this kind of hip pain. The possibility of hip osteoarthritis should not be underestimated, as this could lead to an incorrect diagnosis and inappropriate spinal surgery. We report the case of a 54-year-old female with chronic right anterior and lateral leg pain who did not respond to repeated spinal blocks based on lumbar MRI, but in whom hip osteoarthritis was considered since severe atrophy of the ipsilateral psoas muscle was identified. We suggest that severe psoas muscle atrophy can be a clinical clue to identify hip osteoarthritis and is related to lower extremity pain, even if there is a coexisting lumbar spine pathology. Full article

Background and objectives: Respiratory muscle fatigue is one of the important factors limiting sports performance due to the metaboreflex. This reflex will cause a decrease in blood flow to the extremities and accelerate exercising limb fatigue. Previous studies found that inspiratory muscle training (IMT) can effectively enhance the respiratory muscle endurance and reduce fatigue during long-duration exercise or aerobic exercise, thereby enhancing athletic performance. However, the mechanism between inspiratory muscle strength, change of limb blood flow and sports performance still requires investigation, especially in short-duration exercise, anaerobic or both aerobic and anaerobic exercise. The purpose of this study was to investigate the effects of 4-week inspiratory muscle training on respiratory muscle strength, limb blood flow change rate and sports performance in recreational 800-m college runners. Materials and Methods: Twenty healthy 800-m college runners randomized into the IMT group (11 subjects) and control group (9 subjects). IMT consisted of 30 inspiratory efforts twice daily, 5 days a week, with intensity at 50%, 60%, 70% and 80% of maximum inspiratory pressure (MIP) for 4 weeks, while a control group kept 50% of MIP for 4 weeks. An 800-m trial test, limb blood flow change rate by using Impedance Plethysmography, and MIP were as the outcome measured variables and be evaluated. All measured variables were assessed before and after 4-week IMT training. Two-way ANOVA was conducted for statistical analysis. Results: The results showed significantly interaction between groups and pre-posttest. IMT group significantly decreased limb blood flow change rate from 19.91 ± 11.65% to 9.63 ± 7.62% after received the IMT training program (p < 0.05). The MIP significantly improved from 112.95 ± 27.13 cmH₂O to 131.09 ± 28.20 cm H₂O in IMT group, and the 800-m trial test also shorted the running time from 162.97 ± 24.96 s to 156.75 ± 20.73 s. But the control group no significantly changed in MIP and 800-m trial test. Conclusions: Our results indicated that the 4-week IMT training (twice a day, 5 days a week) significantly improves participants’ inspiratory muscle strength, 800-m running performance and decreases the limb blood flow change rate. Full article

Background and Objectives: Although there have been research on bone cutting, there have been few research on bone grinding. This study reports the measurement results of the experimental system that simulated partial laminectomy in microscopic spine surgery. The purpose of this study was to examine the fluid lubrication and cooling in bone grinding, histological characteristics of workpieces, and differences in grinding between manual and milling machines. Materials and Methods: Thiel-fixed human iliac bones were used as workpieces. A neurosurgical microdrill was used as a drill system. The workpieces were fixed to a 4-component piezo-electric dynamometer and fixtures, which was used to measure the triaxial power during bone grinding. Grinding tasks were performed by manual activity and a small milling machine with or without water. Results: In bone grinding with 4-mm diameter diamond burs and water, reduction in the number of sudden increases in grinding resistance and cooling effect of over 100 °C were confirmed. Conclusion: Manual grinding may enable the control of the grinding speed and cutting depth while giving top priority to uniform torque on the work piece applied by tools. Observing the drill tip using a triaxial dynamometer in the quantification of surgery may provide useful data for the development of safety mechanisms to prevent a sudden deviation of the drill tip. Full article

Background and objectives: This study aimed to determine the frailty, prognosis, complexity, and palliative care complexity of nursing home residents with palliative care needs and define the characteristics of the cases eligible for receiving advanced palliative care according to the resources available at each nursing home. Materials and Methods: In this multi-centre, descriptive, and cross-sectional study, trained nurses from eight nursing homes in southern Spain selected 149 residents with palliative care needs. The following instruments were used: the Frail-VIG index, the case complexity index (CCI), the Diagnostic Instrument of Complexity in Palliative Care (IDC-Pal), the palliative prognosis index, the Barthel index (dependency), Pfeiffer’s test (cognitive impairment), and the Charlson comorbidity index. A consensus was reached on the complexity criteria of the Diagnostic Instrument of Complexity in Palliative Care that could be addressed in the nursing home (no priority) and those that required a one-off (priority 2) or full (priority 1) intervention of advanced palliative care resources. Non-parametric tests were used to compare non-priority patients and patients with some kind of priority. Results: A high percentage of residents presented frailty (80.6%), clinical complexity (80.5%), and palliative care complexity (65.8%). A lower percentage of residents had a poor prognosis (10.1%) and an extremely poor prognosis (2%). Twelve priority 1 and 14 priority 2 elements were identified as not matching the palliative care complexity elements that had been previously identified. Of the studied cases, 20.1% had priority 1 status and 38.3% had priority 2 status. Residents with some kind of priority had greater levels of dependency (p < 0.001), cognitive impairment (p < 0.001), and poorer prognoses (p < 0.001). Priority 1 patients exhibited higher rates of refractory delirium (p = 0.003), skin ulcers (p = 0.041), and dyspnoea (p = 0.020). Conclusions: The results indicate that there are high levels of frailty, clinical complexity, and palliative care complexity in nursing homes. The resources available at each nursing home must be considered to determine when advanced palliative care resources are required. Full article

In the acute cardiac care setting, undifferentiated clinical presentations such as dyspnea, chest pain, shock, and cardiac arrest are common diagnostic challenges for the clinician. Lung ultrasonography is a well-established diagnostic tool which can be integrated in simplified decision making algorithms during the initial approach of the patient, in order to differentiate accurately cardiac from non-cardiac causes and improve the management of time-sensitive cardiovascular emergencies. Full article

Background and objectives: Critically and non-critically ill patients with SARS-CoV-2 infection (Covid-19) may present with higher-than-expected glycemia, even in the absence of diabetes. With this study we aimed to assess glucose, glycemic gap (GlyG) and insulin secretion/sensitivity measures in patients with Covid-19. Materials and Methods: We studied, upon admission, 157 patients with Covid-19 (84: in wards and 73: in intensive care units; ICU); 135 had no history of diabetes. We measured blood glucose upon admission as well as glycated hemoglobin (A1c), plasma insulin and C-peptide. We calculated the GlyG and the Homeostasis Model Assessment 2 (HOMA2) estimates of steady state beta cell function (HOMA2%B) and insulin sensitivity (HOMA2%S). Statistical assessment was done with analysis or the Kruskal-Wallis test. Results: Compared to patients in the wards without diabetes, patients with diabetes in the wards, as well as patients in the ICU (without or with diabetes) had higher admission glycemia. The GlyG was significantly higher in patients without diabetes in the ICU compared to patients without diabetes in the wards, while HOMA2%B based on glucose and insulin was significantly higher in the ICU patients compared to patients in the wards. Of all the parameters, HOMA2%S based on C-peptide/glucose was higher in survivors (n = 133). Conclusions: In our series of patients with Covid-19, a substantial number of patients with and without diabetes had admission hyperglycemia and those who were critically ill may have had compromised insulin secretion and lowered sensitivity to insulin. These findings lend credence to reports of association between Covid-19 and hyperglycemia/secondary diabetes. Full article

Background and Objectives: Hazelnuts are frequently involved in IgE-mediated reactions and represent the main culprit of nut allergy in Europe. The clinical presentation varies from mild symptoms limited to the oropharynx [oral allergy syndrome (OAS)], due to the cross-reaction with homologues in pollen allergens and more severe events caused by the primary sensitization to highly stable molecules contained in hazelnuts. The aim of this review is to summarize the most relevant concepts in the field of hazelnut allergy and to provide a practical approach useful in the clinical practice Materials and Methods: References were identified by PubMed searches dating from January 2000 up to November 2020 using the search terms: “component resolved diagnosis” and “Hazelnut allergy. Results: The storage proteins Cor a 9 and Cor a 14 resulted highly specific for primary hazelnut allergy and strongly associated with severe reactions, while the cross reactive Cor a 1, an homolog of the birch Bet v1, were related to OAS. Any cut-off has shown a specificity and sensitivity pattern as high as to replace the oral food challenge (OFC), which still remains the gold standard in the diagnosis of hazelnut allergy. To date there is still no definitive treatment. Hazelnut free-diet and treatment of symptoms with emergency management, including the prescription of auto-injective epinephrine, still represent the main approach. Oral allergen immunotherapy (AIT) appears a promising therapeutic strategy and the definition of individual clinical threshold would be useful for sensitized individuals, caregivers, and physicians to reduce social limitation, anxiety, and better manage food allergy. Conclusions: An accurate diagnostic work-up including clinical history, in vivo and in vitro test including component resolved diagnosis and OFC are essential to confirm the diagnosis, to assess the risk of a severe reaction, and to prescribe an adequate diet and treatment. Full article

Obesity represents a health problem resulting from a broken balance between energy intake and energy expenditure leading to excess fat accumulation. Elucidating molecular and cellular pathways beyond the establishment of obesity remains the main challenge facing the progress in understanding obesity and developing its treatment. Within this context, this opinion presents obesity as a reprogrammer of selected neurological and endocrine patterns in order to adapt to the new metabolic imbalance represented by obesity status. Indeed, during obesity development, the energy balance is shifted towards increased energy storage, mainly but not only, in adipose tissues. These new metabolic patterns that obesity represents require changes at different cellular and metabolic levels under the control of the neuroendocrine systems through different regulatory signals. Therefore, there are neuroendocrine changes involving diverse mechanisms, such as neuroplasticity and hormonal sensitivity, and, thus, the modifications in the neuroendocrine systems in terms of metabolic functions fit with the changes accompanying the obesity-induced metabolic phenotype. Such endocrine reprogramming can explain why it is challenging to lose weight once obesity is established, because it would mean to go against new endogenous metabolic references resulting from a new “setting” of energy metabolism-related neuroendocrine regulation. Investigating the concepts surrounding the classification of obesity as a neuroendocrine reprogrammer could optimize our understanding of the underlying mechanisms and, importantly, reveal some of the mysteries surrounding the molecular pathogenesis of obesity, as well as focusing the pharmacological search for antiobesity therapies on both neurobiology synaptic plasticity and hormonal interaction sensitivity. Full article

Background and Objectives: There is a paucity of integrated knowledge regarding legal considerations required to ensure patient safety through safe medicines management. This study explores the legal considerations surrounding medicines management, providing a synthesis of existing knowledge. An integrative systematic review of the current international knowledge was performed. Materials and Methods: The search encompassed the online databases of PubMed (including Medline), Scopus, CINAHL, and Web of Science using MeSH terms and relevant keywords relating to the legal considerations of medicines management in healthcare settings. Results: The search process led to the identification of 6051 studies published between 2010 and 2020, of which six articles were found to be appropriate for data analysis and synthesis based on inclusion criteria. Research methods were varied and included qualitative interviews, mixed-methods designs, retrospective case reports and cross-sectional interrupted time-series analysis. Their foci were on the delegation of medicines management, pharmacovigilance and reporting of adverse drug reactions (ADRs) before and after legislation by nurses, physicians and pharmacists, medico-legal litigation, use of forced medication and the prescription monitoring program. Given the heterogenicity of the studies in terms of aims and research methods, a meta-analysis could not be performed and, therefore, our review findings are presented narratively under the categories of ‘healthcare providers’ education and monitoring tasks’, ‘individual and shared responsibility’, and ‘patients’ rights’. Conclusion: This review identifies legal aspects surrounding medicines management, including supervision and monitoring of the effects of medicines; healthcare providers’ knowledge and attitudes; support and standardised tools for monitoring and reporting medicines’ adverse side effects/ADRs; electronic health record systems; individual and shared perceptions of responsibility; recognition of nurses’ roles; detection of sentinel medication errors; covert or non-voluntary administration of medication, and patient participation. Full article

Background and objectives: Choroideremia (CHM) is an X-linked recessive chorioretinal dystrophy caused by mutations involving the CHM gene. Gene therapy has entered late-phase clinical trials, although there have been variable results. This review gives a summary on the outcomes of phase I/II CHM gene therapy trials and describes other potential experimental therapies. Materials and Methods: A Medline (National Library of Medicine, Bethesda, MD, USA) search was performed to identify all articles describing gene therapy treatments available for CHM. Results: Five phase I/II clinical trials that reported subretinal injection of adeno-associated virus Rab escort protein 1 (AAV2.REP1) vector in CHM patients were included. The Oxford study (NCT01461213) included 14 patients; a median gain of 5.5 ± 6.8 SD (−6 min, 18 max) early treatment diabetic retinopathy study (ETDRS) letters was reported. The Tubingen study (NCT02671539) included six patients; only one patient had an improvement of 17 ETDRS letters. The Alberta study (NCT02077361) enrolled six patients, and it reported a minimal vision change, except for one patient who gained 15 ETDRS letters. Six patients were enrolled in the Miami trial (NCT02553135), which reported a median gain of 2 ± 4 SD (−1 min, 10 max) ETDRS letters. The Philadelphia study (NCT02341807) included 10 patients; best corrected visual acuity (BCVA) returned to baseline in all by one-year follow-up, but one patient had −17 ETDRS letters from baseline. Overall, 40 patients were enrolled in trials, and 34 had 2 years of follow-up, with a median gain of 1.5 ± 7.2 SD (−14 min, 18 max) in ETDRS letters. Conclusions: The primary endpoint, BCVA following gene therapy in CHM, showed a marginal improvement with variability between trials. Optimizing surgical technique and pre-, peri-, and post-operative management with immunosuppressants to minimize any adverse ocular inflammatory events could lead to reduced incidence of complications. The ideal therapeutic window needs to be addressed to ensure that the necessary cell types are adequately transduced, minimizing viral toxicity, to prolong long-term transgenic potential. Long-term efficacy will be addressed by ongoing studies. Full article

Background and objective: The early detection of underlying hemorrhage of pelvic trauma has been a critical issue. The aim of this study was to systematically determine the diagnostic accuracy of computed tomography (CT) for detecting severe pelvic hemorrhage. Materials and Methods: Relevant articles were obtained by searching PubMed, EMBASE, and Cochrane databases through 28 November 2020. Diagnostic test accuracy results were reviewed to obtain the sensitivity, specificity, diagnostic odds ratio, and summary receiver operating characteristic curve of CT for the diagnosis in pelvic trauma patients. The positive finding on CT was defined as the contrast extravasation. As the reference standard, severe pelvic hemorrhage was defined as an identification of bleeding at angiography or by direct inspection using laparotomy that required hemostasis by angioembolization or surgery. A subgroup analysis was performed according to the CT modality that is divided by the number of detector rows. Result: Thirteen eligible studies (29 subsets) were included in the present meta-analysis. Pooled sensitivity of CT was 0.786 [95% confidence interval (CI), 0.574–0.909], and pooled specificity was 0.944 (95% CI, 0.900–0.970). Pooled sensitivity of the 1–4 detector row group and 16–64 detector row group was 0.487 (95% CI, 0.215–0.767) and 0.915 (95% CI, 0.848–0.953), respectively. Pooled specificity of the 1–4 and 16–64 detector row groups was 0.956 (95% CI, 0.876–0.985) and 0.906 (95% CI, 0.828–0.951), respectively. Conclusion: Multi-detector CT with 16 or more detector rows has acceptable high sensitivity and specificity. Extravasation on CT indicates severe hemorrhage in patients with pelvic trauma. Full article

Triple-negative breast cancer (TNBC) is an aggressive breast type of cancer with no expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2). It is a highly metastasized, heterogeneous disease that accounts for 10–15% of total breast cancer cases with a poor prognosis and high relapse rate within five years after treatment compared to non-TNBC cases. The diagnostic and subtyping of TNBC tumors are essential to determine the treatment alternatives and establish personalized, targeted medications for every TNBC individual. Currently, TNBC is diagnosed via a two-step procedure of imaging and immunohistochemistry (IHC), which are operator-dependent and potentially time-consuming. Therefore, there is a crucial need for the development of rapid and advanced technologies to enhance the diagnostic efficiency of TNBC. This review discusses the overview of breast cancer with emphasis on TNBC subtypes and the current diagnostic approaches of TNBC along with its challenges. Most importantly, we have presented several promising strategies that can be utilized as future TNBC diagnostic modalities and simultaneously enhance the efficacy of TNBC diagnostic. Full article

Background and objectives: An Italian nationwide pre-participation screening approach for prevention of sudden cardiac death in athletes (SCD-A) in competitive sportspeople showed promising results but did not achieve international consensus, due to cost-effectiveness and the shortfall of a monitoring plan. From this perspective, we tried to provide an epidemiological update of SCD-A in Italy through a year-long internet-based search. Materials and Methods: One year-long Google search was performed using mandatory and non-mandatory keywords. Data were collected according to prevalent SCD-A definition and matched with sport-related figures from Italian National Institute of Statistics (ISTAT) and Italian National Olympic Committee (CONI). Results: Ninety-eight cases of SCD-A in 2019 were identified (48.0% competitive, 52.0% non-competitive athletes). Male/female ratio was 13:1. The most common sports were soccer (33.7%), athletics (15.3%) and fitness (13.3%). A conclusive diagnosis was achieved only in 37 cases (33 of cardiac origin), with the leading diagnosis being coronary artery disease in 27 and a notably higher occurrence among master athletes. Combining these findings with ISTAT and CONI data, the SCD-A incidence rate in the whole Italian sport population was found to be 0.47/100,000 persons per year (1.00/100,000 in the competitive and 0.32/100,000 in the non-competitive population). The relative risk of SCD-A is 3.1 (CI 2.1–4.7; p < 0.0001) for competitive compared to non-competitive athletes; 9.9 for male (CI 4.6–21.4; p < 0.0001) with respect to female. Conclusions: We provided an updated incidence rate of SCD-A in both competitive and non-competitive sport in Italy. A higher risk of SCD-A among competitive and male athletes was confirmed, thus corroborating the value of Italian pre-participation screening in this population. Full article

Background and Objective: Guided bone regeneration allows new bone formation in anatomical sites showing defects preventing implant rehabilitation. Material and Methods: The present case series reported the outcomes of five patients treated with customized titanium meshes manufactured with a digital workflow for achieving bone regeneration at future implant sites. A significant gain in both width and thickness was achieved for all patients. Results: From a radiographic point of view (CBTC), satisfactory results were reached both in horizontal and vertical defects. An average horizontal gain of 3.6 ± 0.8 mm and a vertical gain of 5.2 ± 1.1 mm. Conclusions: The findings from this study suggest that customized titanium meshes represent a valid method to pursue guided bone regeneration in horizontal, vertical or combined defects. Particular attention must be paid by the surgeon in the packaging of the flap according to a correct method called the “poncho” technique in order to reduce the most frequent complication that is the exposure of the mesh even if a partial exposure of one mesh does not compromise the final outcome of both the reconstruction and the healing of the implants. Full article

Effective platelet inhibition is the main goal of the antiplatelet therapy recommended as a standard treatment in the secondary prevention of non-embolic ischemic stroke. Acetylsalicylic acid (aspirin) and clopidogrel are commonly used for this purpose worldwide. A low biological response to antiplatelet agents is a phenomenon that significantly reduces the therapeutic and protective properties of the therapy. The mechanisms leading to high on-treatment platelet reactivity are still unclear and remain multifactorial. The aim of the current review is to establish the background of resistance to antiplatelet agents commonly used in the secondary prevention of ischemic stroke and to explain the possible mechanisms. The most important factors influencing the incidence of a low biological response were demonstrated. The similarities and the differences in resistance to both drugs are emphasized, which may facilitate the selection of the appropriate antiplatelet agent in relation to specific clinical conditions and comorbidities. Despite the lack of indications for the routine assessment of platelet reactivity in stroke subjects, this should be performed in selected patients from the high-risk group. Increasing the detectability of low antiaggregant responders, in light of its negative impact on the prognosis and clinical outcomes, can contribute to a more individualized approach and modification of the antiplatelet therapy to maximize the therapeutic effect in the secondary prevention of stroke. Full article

This article aims to critically review the evidence on the available therapeutic strategies for the treatment of hyperuricemia. For this reason, several papers were reviewed. Xanthine oxidase inhibitors are the safest and most effective uric acid lowering drugs for the management of chronic hyperuricemia, while the efficacy of uricosuric agents is strongly modulated by pharmacogenetics. Emergent drugs (lesinurad, peglotidase) were found to be more effective for the acute management of refractory hyperuricemia, but their use is supported by a relatively small number of clinical trials so that further well-designed clinical research is needed to deepen their efficacy and safety profile. Full article

Background and objectives: Overdiagnosis, overtreatment, and the need for repeated procedures caused by transrectal ultrasound guided prostate biopsies and their related complications places a heavy burden on healthcare systems. This was a prospective cohort validating study to access the clinical accuracy of systematic and MRI-cognitive targeted transperineal prostate biopsies in detecting clinically significant prostate cancer after a previous negative biopsy and persistent suspicion of malignancy. The primary goal was to assess the ability of multiparametric magnetic resonance imaging (mpMRI) to detect clinically significant prostate cancer with an additional goal to assess the diagnostic value of systematic and MRI-cognitive transperineal biopsies. Materials and Methods: In total, 200 patients were enrolled who had rising serum prostate specific antigen (PSA) levels for at least 4 months after a previous negative transrectal ultrasound (TRUS) biopsy. All eligible men underwent 1.5T prostate mpMRI, reported using the Prostate Imaging Reporting and Data System version 2 (PI-RADS v2), followed by a 20-region transperineal prostate systematic biopsy and additional targeted biopsies. Results: Systematic 20-core transperineal prostate biopsies (TPBs) were performed for 38 (19%) patients. Systemic 20-core TPB with additional cognitive targeted biopsies were performed for 162 (81%) patients. Clinically significant prostate cancer (csPC) was detected for 31 (15.5%) patients, of which 20 (64.5%) cases of csPC were detected by systematic biopsy, eight (25.8%) cases were detected by targeted biopsy, and three (9.7%) both by systematic and targeted biopsies. Conclusions: Cognitive mpMRI guided transperineal target biopsies increase the detection rate of clinically significant prostate cancer after a previously negative biopsy. However, in a repeat prostate biopsy setting, we recommend applying a cognitive targeted biopsy with the addition of a systematic biopsy. Full article

Background and Objectives: Vesicoureteral reflux (VUR) describes a common pediatric anomaly in pediatric urology with a prevalence of 1–2%. In diagnostics, in addition to the gold standard of voiding cystourethrography (VCUG), contrast-enhanced urosonography (ceVUS) offers a radiation-free procedure, which, despite its advantages, is not yet widely used. In the present single-center study, subsequent therapeutic procedures and outcomes after ceVUS of 49 patients were investigated. The aim of the study is to investigate the efficacy of ceVUS with the intention of broader clinical implementation. Materials and Methods: Between 2016 and 2020, 49 patients were retrospectively included and received a ceVUS to evaluate VUR. With a distribution of 47:2 (95.9%), a clear female predominance was present. The age of the patients varied between 5 months and 60 years at the time of ceVUS. All examinations were all performed and subsequently interpreted by a single experienced radiologist (EFSUMB level 3). Results: Compared to intraoperative findings, ceVUS shows a sensitivity of 95.7% with a specificity of 100%. Allergic reactions to the contrast medium could not be observed. Conclusion: With its high sensitivity and intraoperative validation, ceVUS offers an excellent alternative to VCUG, the gold standard in the diagnosis of VUR. In addition, ceVUS is a radiation-free examination method with a low risk profile that offers an exceptional diagnostic tool in the diagnostic clarification of recurrent urinary tract infections with the suspected diagnosis of VUR and should also be included in the consideration of a diagnosis next to the established VCUG, especially in younger children. Full article

Nowadays, humanity faces one of the most serious health crises, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. The severity of coronavirus disease 2019 (COVID-19) pandemic is related to the high rate of interhuman transmission of the virus, variability of clinical presentation, and the absence of specific therapeutic methods. COVID-19 can manifest with non-specific symptoms and signs, especially among the elderly. In some cases, the clinical manifestations of hyponatremia may be the first to appear. The pathophysiological mechanisms of hyponatremia among patients with COVID-19 are diverse, including syndrome of inappropriate antidiuretic hormone secretion (SIADH), digestive loss of sodium ions, reduced sodium ion intake or use of diuretic therapy. Hyponatremia may also be considered a negative prognostic factor in patients diagnosed with COVID-19. We need further studies to evaluate the etiology and therapeutic management of hyponatremia in patients with COVID-19. Full article

Background and objectives: Bipolar disorder (BD) is one of the most burdensome psychiatric illnesses, being associated with a negative long-term outcome and the highest suicide rate. Although affective temperaments can impact on BD long-term outcome, their role remains poorly investigated. The aims of the present study are to describe the clinical characteristics of patients with BD more frequently associated with the different affective temperaments and to assess the relation between affective temperaments and severity of clinical picture in a sample of patients with BD. Materials and Methods: A total of 199 patients have been recruited in the outpatients units of two university sites. Patients’ psychiatric symptoms, affective temperaments, and quality of life were investigated through validated assessment instruments. Results: Predominant cyclothymic and irritable temperaments are associated to higher number of relapses, poorer quality of life, higher rates of aggressive behaviors, and suicide attempts. Conversely, the predominant hyperthymic disposition was a protective factor for several outcome measures, including relapse rate, severity of anxiety, depressive and manic symptoms, suicidality, and earlier age at onset. One limitation of the present study is that the recruitment took place in two university sites; therefore, our findings cannot be fully generalized to the whole community of BD patients. Other limitations are the lack of a control group and the cross-sectional design of the study. Conclusions: The early identification of affective temperaments can help clinicians to identify those BD patients who are more likely to show a poor long-term outcome. An early screening of affective temperaments can be useful to develop targeted integrated pharmacological and psychosocial interventions. Full article

Background: The COVID-19 pandemic poses a challenge to global mental health. Loneliness and isolation may put people at higher risk for increased psychological distress. However, there is a lack of research investigating the development of COVID-19-related distress over time. Materials and Methods: We undertook an online survey among general population (N = 1903) in Germany throughout 6 months from the peak transmission period in April to the off-peak period by September 2020. Results: We found that the average prevalence of psychological distress caused by the COVID-19 pandemic significantly rose from 24% to 66% between the peak and off-peak transmission period, respectively. Unemployment rate and loneliness increased negative mental health outcomes, although the number of active COVID-19 cases decreased from April to September. Psychological distress scores increased mostly in female, young, and lonely people. Conclusions: Our results underline the importance of considering innovative alternatives to facilitate employment opportunities, distant contacts, and self-help over the course of the pandemic. Our study highlights the urgent need to pay attention to mental health services specifically targeting female, young, unemployed, and lonely people. Full article

Background and objectives: The COVID-19 outbreak has become a major health and economic crisis. The World Health Organization declared it a pandemic in March 2020, and many sporting events were canceled. Materials and Methods: We examined the effects of the COVID-19 pandemic on endurance and ultra-endurance running (UER) and analyzed finishes and events during the COVID-19 pandemic (observation period March 2020–October 2020) to the same time period pre-COVID-19 outbreak (March 2019–October 2019). Results: Endurance finishes decreased during the pandemic (459,029 to 42,656 (male: 277,493 to 25,582; female 181,536 to 17,074; all p < 0.001). Similarly, the numbers of endurance events decreased (213 vs. 61 events; p < 0.001). Average marathon finishing times decreased during the pandemic in men (5:18:03 ± 0:16:34 vs. 4:43:08 ± 0:25:08 h:min:s (p = 0.006)) and women (5:39:32 ± 0:19:29 vs. 5:14:29 ± 0:26:36 h:min:s (p = 0.02)). In UER, finishes decreased significantly (580,289 to 110,055; p < 0.001) as did events (5839 to 1791; p < 0.001). Popular event locations in United States, France, UK, and Germany decreased significantly (p < 0.05). All distance and time-limited UER events saw significant decreases (p < 0.05). Conclusions: The COVID-19 pandemic has had a significant effect on endurance and UER, and it is unlikely that running activities return to pre-pandemic levels any time soon. Mitigation strategies and safety protocols should be established. Full article