J. Clin. Med., Volume 10, Issue 16 (August-2 2021) – 311 articles

A family history of melanoma greatly increases the risk of developing cutaneous melanoma, a highly aggressive skin cancer whose incidence has been steadily increasing worldwide. Familial melanomas account for about 10% of all malignant melanomas and display an inheritance pattern consistent with the presence of pathogenic germline mutations, among which those involving CDKN2A are the best characterized. In recent years, a growing number of genes, such as MC1R, MITF, CDK4, POT1, TERT, ACD, TERF2IP, and BAP1, have been implicated in familial melanoma. The fact that individuals harboring these germline mutations along with their close blood relatives have a higher risk of developing multiple primary melanomas as well as other internal organ malignancies, especially pancreatic cancer, makes cascade genetic testing and surveillance of these families of the utmost importance. Unfortunately, due to a polygenic inheritance mechanism involving multiple low-risk alleles, genetic modifiers, and environmental factors, it is still very difficult to predict the presence of these mutations. It is, however, known that germline mutation carriers can sometimes develop specific clinical traits, such as high atypical nevus counts and specific dermoscopic features, which could theoretically help clinicians predict the presence of these mutations in prone families. In this review, we provide a comprehensive overview of the high- and intermediate-penetrance genes primarily linked to familial melanoma, highlighting their most frequently associated non-cutaneous malignancies and clinical/dermoscopic phenotypes. Full article

Background: Perioperative management of pheochromocytoma (PCC) remains under debate. Methods: A bicentric retrospective study was conducted, including all patients who underwent laparoscopic adrenalectomy for PCC from 2000 to 2017. Patients were divided into two groups: Group 1 treated with alpha-blockade, and Group 2, without alfa-blockers. The primary end point was the major complication rate. The secondary end points were: the need for advanced intra-operative hemostasis, the admission to the intensive care unit (ICU), the length of stay (LOS), systolic (SBP), and diastolic blood pressure (DBP). Univariate and multivariate analysis was conducted. A p-value < 0.05 was considered statistically significant. Results: Major postoperative complications were similar (p = 0.49). Advanced hemostatic agents were 44.9% in Group 1 and 100% in Group 2 (p < 0.001). In Group 2, no patients were admitted to the ICU, while only 73.5% of Group 1 (p < 0.001) were admitted. The median length of stay was larger in Group 1 than in Group 2 (p = 0.026). At the induction, SBP was 130 mmHg in Group 1, and 115 mmHg (p < 0.001). The pre-surgery treatment was the only almost statistically significant variable at the multivariate analysis of DBP at the end of surgery. Conclusion: The preoperative use of alfa-blockers should be considered not a dogma in PCC. Full article

Preeclampsia (PE) is a major disease of pregnancy, with various short- or long-term complications for both the mother and offspring. We focused on the body mass index (BMI) of offspring and compared the incidence of obesity during early childhood between PE- and non-PE-affected pregnancies. Women with singleton births (n = 1,697,432) were identified from the Korea National Health Insurance database. The outcomes of offspring at 30–80 months of age were analyzed. The effects of PE on BMI and the incidence of obesity in the offspring were compared. The incidence of low birth weight (LBW) offspring was higher in the PE group (n = 29,710) than that in the non-PE group (n = 1,533,916) (24.70% vs. 3.33%, p < 0.01). However, BMI was significantly higher in the PE-affected offspring than that in non-PE-affected offspring. After adjusting for various factors, the risk of obesity was higher in the PE-affected offspring (odds ratio = 1.34, 95% confidence interval = 1.30–1.38). The BMI and incidence of obesity were higher during early childhood in the PE-affected offspring, even though the proportion of LBW was higher. These results may support the basic hypotheses for the occurrence of various cardiovascular and metabolic complications in PE-affected offspring. In addition, early-age incidence of obesity could influence PE management and child consultation in clinical applications. Full article

Pulmonary arterial hypertension (PAH) is a relatively rare disease, but, today, its incidence tends to increase. The severe course of the disease and poor patient survival rate make PAH a major diagnostic and therapeutic challenge. For this reason, a thorough understanding of the pathogenesis of the disease is essential to facilitate the development of more effective therapeutic targets. Research shows that the development of PAH is characterized by a number of abnormalities within the immune system that greatly affect the progression of the disease. In this review, we present key data on the regulated function of immune cells, released cytokines and immunoregulatory molecules in the development of PAH, to help improve diagnosis and targeted immunotherapy. Full article

Patiromer is a calcium (Ca)-potassium (K) exchange resin approved for the treatment of hyperkalemia. Disorders of Ca or acid base balance were not reported in pre-approval clinical trials. We present a case of a patient with chronic kidney disease (CKD) with an unusual picture of hypercalcemia, metabolic alkalosis and hypokalemia upon intensification of patiromer dosing. A 56-year-old white man with CKD stage 4 (baseline creatinine 2.8 mg/dL) due to type 1 diabetes mellitus, proteinuria (1.5 g/g) and persistently high serum potassium 5.9 mEq/L attributed to type 4 renal tubular acidosis was evaluated in clinic. Due to high risk of CKD progression, patiromer 8.4 g daily, followed by 16.8 g daily was prescribed to enable renin angiotensin aldosterone system (RAAS) inhibitor. After 5 months of being on patiromer 16.8 g daily, routine laboratory tests revealed serum potassium 2.5 mEq/L, serum calcium 12.8 mg/dL and carbon dioxide 34 mEq/L. Patiromer was discontinued and thorough investigation held was negative for other causes of hypercalcemia. Five days after patiromer discontinuation, serum calcium returned to normal. The role of secondary hyperparathyroidism in this case remains unclear. We, therefore recommend cautious vigilance of patients receiving patiromer and undergoing dose escalation. Full article

Background: Selenium (Se) is an essential component of selenoenzymes, which have catalytic and antioxidant functions. A low Se status has been reported in patients with chronic autoimmune thyroiditis (AT) who benefit from Se supplementation. The role of Se in male reproduction is still a matter of debate. Although Se and selenoenzymes ensure sperm viability and protect against increased oxidative stress, only a few studies have assessed the effects of the administration of Se alone on sperm parameters, providing contrasting results. Aim: The aim of this study was to assess the effects of oral Se supplementation on conventional sperm parameters and DNA fragmentation (SDF) in patients with AT of reproductive age with normal thyroid function. Patients and Methods: Only patients with AT and normal thyroid function were selected for this study. All included patients underwent oral Se supplementation at the dose of 83 µg once daily (Syrel^®, IBSA) for six months. Sperm conventional parameters, SDF, and thyroid function were assessed before and at the end of the treatment. Results: Twenty AT patients with normal weight were enrolled. After Se supplementation, they showed a higher sperm concentration, a higher percentage of sperm with progressive motility, and a higher percentage with normal morphology. They also had lower semen leukocyte concentration, and a lower percentage of spermatozoa with DNA fragmentation compared with pre-treatment values. Free-thyroxine serum levels increased significantly, whereas free triiodothyronine showed an upward trend. The thyroid-stimulating hormone did not change significantly. Conclusion: Se supplementation may represent a possible non-hormonal therapeutic choice for the treatment of male infertility, although further studies are needed to confirm this evidence. The possible thyroid hormone dependency of these findings needs to be clarified. Full article

Patient-reported outcome (PRO) instruments are widely used to assess quality of life in Systemic Lupus Erythematosus (SLE) research, and there is growing evidence for their use in clinical care. In this review, we evaluate the current evidence for their use in assessing quality of life in SLE in both research and clinical settings and examine the different characteristics of the commonly used PRO tools. There are now several well-validated generic and SLE-specific tools that have demonstrated utility in clinical trials and several tools that complement activity and damage measures in the clinical setting. PRO tools may help overcome physician–patient discordance in SLE and are valuable in the assessment of fibromyalgia and type 2 symptoms such as widespread pain and fatigue. Future work will identify optimal PRO tools for different settings but, despite current limitations, they are ready to be incorporated into patient care. Full article

(1) Background: We aim to analyze sex differences in the incidence, clinical characteristics and in-hospital outcomes of hemorrhagic stroke (HS) in Spain (2016–2018) using the National Hospital Discharge Database. (2) Methods: Retrospective, cohort, observational study. We estimated the incidence of HS in men and women. We analyzed comorbidity, treatments, procedures, and hospital outcomes. We matched each woman with a man by age, type of HS and medical conditions using propensity score matching. (3) Results: HS was coded in 57,227 patients aged ≥18 years (44.3% women). Overall, men showed higher incidence rates (57.3/10⁵ vs. 43.0/10⁵; p < 0.001; IRR = 1.60; 95% CI: 1.38–1.83). Women suffered more subarachnoid hemorrhages (25.2% vs. 14.6%), whereas men more often had intracerebral hemorrhages (55.7% vs. 54.1%). In-hospital mortality (IHM) was higher for intracerebral hemorrhage in both men and women. Women underwent decompressive craniectomy less often than men (5.0% vs. 6.2%; p < 0.001). After matching, IHM among women was higher (29.0% vs. 23.7%; p < 0.001). Increments in age, comorbidity and use of anticoagulants and antiplatelet agents prior to hospitalization were associated were higher IHM, and decompressive craniectomy was associated with lower IHM in both sexes. After multivariable adjustment, women had higher IHM (OR = 1.23; 95% CI: 1.18–1.28). (4) Conclusion: Men had higher incidence rates of HS than women. Women less often underwent decompressive craniectomy. IHM was higher among women admitted for HS than among men. Full article

Jak inhibitors are potent anti-inflammatory drugs that have the potential to dampen the hyperactive inflammatory response associated with severe COVID-19. We reviewed the clinical outcomes of 218 patients with COVID-19 hospitalized for severe pneumonia and treated with ruxolitinib through a compassionate use program. Data on the duration of treatment; outcomes at 4, 7, 14, and 28 days; oxygen support requirements; clinical status; and laboratory parameters were retrospectively collected. Overall, according to the physician evaluation, 66.5% of patients showed improvement at follow-up; of these, 83.5% showed improvement by day 7. Oxygen support status also showed improvement, and by day 7, 21.6% of patients were on ambient air, compared with 1.4% at baseline, which increased to 48.2% by day 28. Significant decreases in C-reactive protein and increases in the lymphocyte total count were already observed by day 4, which seemed to correlate with a positive outcome. At the end of the observation period, 87.2% of patients were alive. No unexpected safety findings were observed, and grade 3/4 adverse events were reported in 6.9% of patients. Full article

Background and Objectives: Pelvic organ prolapse (POP) and osteoporosis are major disease entities in older women that have the same epidemiology and might also have the same molecular physiology. However, few data have been reported on the relationship between POP and osteoporosis. We designed this study to examine the association between POP and osteoporosis in Korean women. Materials and Methods: We used the Health Insurance Review and Assessment Service 2015 to 2017 National Patient Sample (HIRA-NPS). A total of 4,368,141 individuals were included in this study, and a total of 842,228 individuals aged 50 years and above were included in the final analysis. POP patients were defined by the Korean Informative Classification of Diseases (KOICD) codes (KCD-7, N81, or N99.3) and patients who underwent a pelvic reconstructive procedure. The osteoporosis patients were defined by KOICD (KCD-7, R4113, R3620, R0402,) who were prescribed osteoporosis medication. A 1:10 age-stratified matching and chi-squared test were used for statistical analysis, and p < 0.05 was considered as significant. Results: A total of 7359 women were included in this analysis. Advanced POP was correlated with osteoporosis in Korean women aged 50 years and above in 2015–2017 (p < 0.0001). After adjusting for age, advanced POP was correlated with osteoporosis in the 2015, 2016, and 2017 dataset (p = 0.013, 0.0009, 0.0119, respectively). Conclusions: Advanced POP is correlated with osteoporosis in Korean women aged 50 years and above. Evaluation for osteoporosis and education about bone health can be especially important, even in relatively young women, aged 50–59 years, and POP patients. Full article

Background: Patients undergoing kidney transplantation (KT) often receive red blood cell (RBC) transfusion during admission for KT which may increase the risk of allosensitization. The association between peri-transplant RBC transfusion and graft survival was evaluated using a nationwide cohort. Methods: This retrospective study analyzed 13,871 patients who underwent KT in Korea between 2007 and 2015. The outcomes were graft failure rate and overall patient survival depending on the amount of RBC transfusion. Results: The overall graft failure rate was 15.5%. Compared to the graft failure rate of 13.5% in the no transfusion group, the graft failure rate was 15.4% in the 1–2 units group (sHR 1.06 (95% CI 0.97–1.17), p = 0.216), 21.4% in the 3–5 units group (sHR 1.39 (1.21–1.61), p < 0.001), and 35.3% in the 6 or more units group (sHR 2.20 (1.70–2.85), p < 0.001). The overall survival rate was 97.5% in the no transfusion group, compared to 95.9% in the 1–2 units group (HR 1.50 (1.22–1.83), p < 0.001), 92.0% in the 3–5 units group (HR 2.43 (1.87–3.15), p < 0.001), and 67.5% in the 6 or more units group (HR 6.81 (5.03–9.22), p < 0.001). Conclusions: Peri-transplant RBC transfusion was independently associated with the increased risk of renal allograft failure and death in KT patients. Full article

Background: Combined hysteroscopy and laparoscopy is a valuable method for diagnosing and treating infertility and benign uterine pathology. Both procedures are minimally invasive, reliable, and safe, with a low complication rate. Aim: In this review, we expose the efficiency and safety of hysterolaparoscopy in the management of infertility and other benign uterine pathologies. Method: We performed a systematic literature review on several databases: PubMed^®/MEDLINE, PMC, Crossref.org, and Web of Science in the last 10 years. Inclusion criteria: Women of reproductive age with primary or secondary infertility and/or benign uterine pathology. Exclusion criteria: pre-puberty, menopause, couple with male infertility. Conclusion: Hysterolaparoscopy is a useful tool to assess infertility and simultaneously diagnose and treat pelvic and uterine lesions. Full article

Whether the increased risk for coronavirus disease 2019 (COVID-19) hospitalization and death observed in Down syndrome (DS) are disease specific or also occur in individuals with DS and non-COVID-19 pneumonias is unknown. This retrospective cohort study compared COVID-19 cases in persons with DS hospitalized in Spain reported to the Trisomy 21 Research Society COVID-19 survey (n = 86) with admissions for non-COVID-19 pneumonias from a retrospective clinical database of the Spanish Ministry of Health (n = 2832 patients). In-hospital mortality rates were significantly higher for COVID-19 patients (26.7% vs. 9.4%), especially among individuals over 40 and patients with obesity, dementia, and/or epilepsy. The mean length of stay of deceased patients with COVID-19 was significantly shorter than in those with non-COVID-19 pneumonias. The rate of admission to an ICU in patients with DS and COVID-19 (4.3%) was significantly lower than that reported for the general population with COVID-19. Our findings confirm that acute SARS-CoV-2 infection leads to higher mortality than non-COVID-19 pneumonias in individuals with DS, especially among adults over 40 and those with specific comorbidities. However, differences in access to respiratory support might also account for some of the heightened mortality of individuals with DS with COVID-19. Full article

This study used independent, real-world, patient-level data to examine whether the dosage or frequency of paclitaxel exposure correlated with mortality during follow up. We conducted a retrospective analysis of patients treated with a drug-coated balloon (DCB) for an atherosclerotic femoropopliteal lesion from February 2013 to December 2018, excluding patients with non-atherosclerotic lesions or restenosis after DCB treatment in another hospital. We investigated the causes of death, comorbidities (including cancer status), and the initial and total cumulative dosages and frequency of paclitaxel use. To determine whether the dosage or frequency of paclitaxel exposure affected mortality during follow up, we analyzed the risk factors for all-cause death by conducting a time-dependent Cox regression analysis that considered demographics, comorbidities, lesion and procedural characteristics, and paclitaxel exposure data (dosage and frequency). Our analysis examined 225 patients (mean age 71 ± 9 years, range 38–93 years, male 81%). During a mean follow-up duration of 35 months (range 1–89 months), 56 patients (24.9%) died from cardiac disorders (16%, including acute myocardial infarction, heart failure, or sudden cardiac arrest), malignancy (14.3%), respiratory failure with pneumonia (12.5%), septic shock (12.5%), or another cause. Univariable and multivariable Cox regression analyses identified age (hazard ratio, HR, 1.057; 95% confidence interval, CI, 1019–1096; p = 0.0032), critical limb ischemia (CLI) (HR, 4135; 95% CI, 2171–7876; p < 0.0001), and the total dosage of paclitaxel (mg) (HR, 1.040; 95% CI, 1006–1074; p = 0.0210) as predictors of mortality during follow up. The subgroup analysis found that the total dosage of paclitaxel (mg) was also a predictor of mortality during follow up in the CLI group (HR, 1.046; 95% CI, 1007–1087, p = 0.0198). The estimated cut-off value of total cumulative paclitaxel dosage for predicting mortality was 12 mg as evaluated by minimum p value approach. This patient-level analysis identified the total cumulative dosage of paclitaxel as a predictor of mortality after the use of paclitaxel-coated balloons. Our results provide limited information about the potential dose–response relationship underlying paclitaxel-associated mortality concerns. Full article

Surgical techniques for obstructive sleep apnea syndrome (OSAS) constantly evolve. This study aims to assess the effectiveness and safety of a new surgical approach for an OSAS pharyngoplasty with a dorsal palatal flap expansion (PDPFEx). A total of 21 participants (mean age 49.9; mean BMI 32.5) underwent a type III sleep study, an endoscopy of the upper airways, a filled medical history, a visual analog scale for snoring loudness, an Epworth Sleepiness Scale, and a Short Form Health Survey-36 questionnaire. A follow-up re-evaluation was performed 11 ± 4.9 months post-operatively. The study group (4 with moderate, 17 with severe OSAS) showed an improvement in all measured sleep study characteristics (p < 0.05), apnea-hypopnea index (pre-median 45.7 to 29.3 post-operatively, p = 0.009, r = 0.394), oxygen desaturation index (pre-median 47.7 and 23.3 post-operatively, p = 0.0005, r = 0.812), mean oxygen saturation (median 92% pre-operatively and median 94% post-operatively, p = 0.0002, r = 0.812), lowest oxygen saturation (p = 0.0001, r = 0.540) and time of sleep spent with blood oxygen saturation less than 90% (p = 0.0001, r = 0.485). The most commonly reported complications were throat dryness (11 patients) and minor difficulties in swallowing (5 patients transient, 3 patients constant). We conclude that a PDPFEx is a promising new surgical method; however, further controlled studies are needed to demonstrate its safety and efficacy for OSAS treatment in adults. Full article

Aortic stenosis is the most common heart valve disease necessitating surgical or percutaneous intervention. Imaging has a central role for the initial diagnostic work-up, the follow-up and the selection of the optimal timing and type of intervention. Referral for aortic valve replacement is currently driven by the severity and by the presence of aortic stenosis-related symptoms or signs of left ventricular systolic dysfunction. This review aims to provide an update of the imaging techniques and seeks to highlight a practical approach to help clinical decision making. Full article

Objectives: Programmed death-1(PD-1)/programmed death ligand-1 (PD-L1) antibodies have clinical benefits for cancer patients facing immune-related adverse events (irAEs). However, the effect of steroid use on the prognosis of patients with non-small cell lung cancer (NSCLC) receiving PD-1 blockade remains unclear. Methods: NSCLC patients with complete response (CR)/partial response (PR) or stable disease (SD)/not evaluable (NE) status plus progression-free survival (PFS) of 180 days after PD-1 blockade from December 2015 to December 2018 were retrospectively registered in our study and were divided into two groups: those with and without systemic steroid use for irAEs. Results: In total, 126 patients who had benefitted from PD-1 blockade were enrolled in our study; among them, 44 received systemic steroids for irAEs, and 82 had no adverse events or, if they did, did not receive systemic steroids. Among the 44 patients requiring steroids, interstitial lung disease (ILD), adrenal insufficiency, diarrhea, and liver dysfunction were observed in 19, 9, 4, and 4 patients, respectively. More side effects were observed in the group treated by steroids. The median PFS and overall survival (OS) in patients with and without systemic steroid use were 11.7 and 16.0 months (p < 0.037) and 35.0 and 41.0 months (p < 0.28), respectively. In univariate and multivariate analyses of survival, systemic steroid treatment for irAEs was significantly associated with PFS. The occurrence of ILD, adrenal insufficiency, and fever was significant in patients who used systemic steroids for irAEs. Conclusions: Patients administered systemic steroids for irAEs due to PD-1 blockade treatment exhibited shorter PFS than those who were not. Systemic steroids might affect survival after PD-1 blockade even for patients who once acquired its clinical benefit. Full article

We comprehensively assessed the criterion-related validity of existing field-based fitness tests used to indicate adult health (19–64 years, with no known pathologies). The medical electronic databases MEDLINE (via PubMed) and Web of Science (all databases) were screened for studies published up to July 2020. Each original study’s methodological quality was classified as high, low and very low, according to the number of participants, the description of the study population, statistical analysis and systematic reviews which were appraised via the AMSTAR rating scale. Three evidence levels were constructed (strong, moderate and limited evidence) according to the number of studies and the consistency of the findings. We identified 101 original studies (50 of high quality) and five systematic reviews examining the criterion-related validity of field-based fitness tests in adults. Strong evidence indicated that the 20 m shuttle run, 1.5-mile, 12 min run/walk, YMCA step, 2 km walk and 6 min walk test are valid for estimating cardiorespiratory fitness; the handgrip strength test is valid for assessing hand maximal isometric strength; and the Biering–Sørensen test to evaluate the endurance strength of hip and back muscles; however, the sit-and reach test, and its different versions, and the toe-to-touch test are not valid for assessing hamstring and lower back flexibility. We found moderate evidence supporting that the 20 m square shuttle run test is a valid test for estimating cardiorespiratory fitness. Other field-based fitness tests presented limited evidence, mainly due to few studies. We developed an evidence-based proposal of the most valid field-based fitness tests in healthy adults aged 19–64 years old. Full article

Overt hyperthyroidism (HT) during pregnancy is associated with a risk of maternal–fetal complications. Antithyroid drugs (ATD) have a potential risk for teratogenic effects and fetal–neonatal hypothyroidism. This study evaluated ATD treatment and thyroid function control during pregnancy, and pregnancy outcome in women with HT. Patients and methods: A retrospective analysis of 36 single fetus pregnancies in 29 consecutive women (median age 30.3 ± 4.7 years) with HT diagnosed before or during pregnancy; a control group of 39 healthy euthyroid pregnant women was used. Results: Twenty-six women had Graves’ disease (GD, 33 pregnancies), 1 had a hyperfunctioning autonomous nodule, and 2 had gestational transient thyrotoxicosis (GTT). Methimazole (MMI) was administered in 22 pregnancies (78.5%), Propylthiouracil (PTU) in 2 (7.1%), switch from MMI to PTU in 4 (14.2%), no treatment in 8 pregnancies (3 with subclinical HT, 5 euthyroid with previous GD remission before conception). In the 8 pregnancies of GD patients diagnosed during gestation or shortly before (<6 weeks), i.e., with fetal exposure to uncontrolled HT, there was 1 spontaneous abortion at 5 weeks (3.4% of all ATD-treated pregnancies), and 1 premature delivery at 32 weeks with neonatal death in 24 h (3.4%); 1 child had neonatal hyperthyroidism (3.3% of live children in GD women) and a small atrial sept defect (4% of live children in ATD treated women). In women treated more than 6 months until conception (20 pregnancies): (a) median ATD doses were lower than those in women diagnosed shortly before or during pregnancy; (b) ATD was withdrawn in 40% of pregnancies in trimester (T)1, all on MMI < 10 mg/day (relapse in 14.2%), and in up to 55% in T3; (c) TSH level was below normal in 37%, 35% and 22% of pregnancies in T1, T2 and T3 respectively; FT4 was increased in 5.8% (T1) and subnormal in 11.75% in T2 and T3; (d) no fetal birth defects were recorded; one fetal death due to a true umbilical cord knot was registered. Mean birth weight was similar in both ATD-treated and control groups. Hyperthyroidism relapsed postpartum in 83% of GD patients (at median 3 ± 2.6 months). Conclusion: In hyperthyroid women with long-term ATD treatment before conception, drugs could be withdrawn in T1 in 40% of them, the thyroid function control was better, and pregnancy and fetal complications were rarer, compared to women diagnosed during pregnancy. Frequent serum TSH and FT4 monitoring is needed to maintain optimal thyroid function during pregnancy. Full article

Alterations in bone mineral density (BMD) have been suggested as independent predictors of survival for several diseases. However, little is known about the role of BMD in the context of critical illness and intensive care medicine. We therefore evaluated the prognostic role of BMD in critically ill patients upon admission to an intensive care unit (ICU). Routine computed tomography (CT) scans of 153 patients were used to assess BMD in the first lumbar vertebra. Results were correlated with clinical data and outcomes. While median BMD was comparable between patients with and without sepsis, BMD was lower in patients with pre-existing arterial hypertension or chronic obstructive pulmonary disease. A low BMD upon ICU admission was significantly associated with impaired short-term ICU survival. Moreover, patients with baseline BMD < 122 HU had significantly impaired overall survival. The prognostic relevance of low BMD was confirmed in uni- and multivariate Cox-regression analyses including several clinicopathological parameters. In the present study, we describe a previously unrecognised association of individual BMD with short- and long-term outcomes in critically ill patients. Due to its easy accessibility in routine CT, BMD provides a novel prognostic tool to guide decision making in critically ill patients. Full article

Background. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected >160 million people around the world. Hypertension (HT), chronic heart disease (CHD), and diabetes mellitus (DM) increase susceptibility to SARS-CoV-2 infection. Aims. We designed this retrospective study to assess the gender differences in hypertensive diabetic SARS-CoV-2 patients. We reported data, by gender differences, on the inflammatory status, on the hospital stays, intensive care unit (ICU) admission, Rx and CT report, and therapy. Methods. We enrolled 1014 patients with confirmed COVID-19 admitted into different Hospitals of Campania from 26 March to 30 June, 2020. All patients were allocated into two groups: diabetic-hypertensive group (DM-HT group) that includes 556 patients affected by diabetes mellitus and arterial hypertension and the non-diabetic- non-hypertensive group (non-DM, non-HT group) comprising 458 patients. The clinical outcomes (i.e., discharges, mortality, length of stay, therapy, and admission to intensive care) were monitored up to June 30, 2020. Results. We described, in the DM-HT group, higher proportion of cardiopathy ischemic (CHD) (47.5% vs. 14.8%, respectively; p < 0.0001) and lung diseases in females compared to male subjects (34.8% vs. 18.5%, respectively; p < 0.0001). In male subjects, we observed higher proportion of kidney diseases (CKD) (11% vs. 0.01%, respectively; p < 0.0001), a higher hospital stay compared to female subjects (22 days vs. 17 days, respectively, p < 0.0001), a higher admission in ICU (66.9% vs. 12.8%, respectively, p < 0.0001), and higher death rate (17.3% vs. 10.7%, respectively, p < 0.0001). Conclusion. These data confirm that male subjects, compared to female subjects, have a higher hospital stay, a higher admission to ICU, and higher death rate. Full article

Ultrasonographic elastography is a modality used to visualize the elastic properties of tissues. Technological advances in ultrasound equipment have supported the evaluation of elastography (EG) in endosonography (EUS). Currently, the usefulness of not only EUS-strain elastography (EUS-SE) but also EUS-shear wave elastography (EUS-SWE) has been reported. We reviewed the literature on the usefulness of EUS-EG for various diseases such as chronic pancreatitis, pancreatic solid lesion, autoimmune pancreatitis, lymph node, and gastrointestinal and subepithelial lesions. The importance of this new diagnostic parameter, “tissue elasticity” in clinical practice might be applied not only to the diagnosis of liver fibrosis but also to the elucidation of the pathogeneses of various gastrointestinal diseases, including pancreatic diseases, and to the evaluation of therapeutic effects. The most important feature of EUS-EG is that it is a non-invasive modality. This is an advantage not found in EUS-guided fine needle aspiration (EUS-FNA), which has made remarkable progress in the field of diagnostics in recent years. Further development of artificial intelligence (AI) is expected to improve the diagnostic performance of EUS-EG. Future research on EUS-EG is anticipated. Full article

Myocardial involvement during SARS-CoV-2 infection has been reported in many prior publications. We aim to study the prevalence and the clinical implications of acute myocardial injury (MIN) during SARS-CoV-2 infection, particularly in older patients. The method includes a longitudinal observational study with all consecutive adult patients admitted to a COVID-19 unit between March–April 2020. Those aged ≥65 were considered as older adult group. MIN was defined as at least 1 high-sensitive troponin (hs-TnT) concentration above the 99th percentile upper reference limit with different sex-cutoff. Results. Among the 634 patients admitted during the period of observation, 365 (58%) had evidence of MIN, and, of them, 224 (61%) were older adults. Among older adults, MIN was associated with longer time to recovery compared to those without MIN (13 days (IQR 6-21) versus 9 days (IQR 5-17); p < 0.001, respectively. In-hospital mortality was significantly higher in older adults with MIN at admission versus those without it (71 (31%) versus 11 (12%); p < 0.001). In a logistic regression model adjusting by age, sex, severity, and Charlson Comorbidity Index, the OR for in-hospital mortality was 2.1 (95% CI: 1.02–4.42; p = 0.043) among those older adults with MIN at admission. Older adults with acute myocardial injury had greater time to clinical recovery, as well as higher odds of in-hospital mortality. Full article

The surgical treatment of head and neck malignancies relies on the complete removal of tumoral tissue, while inadequate margins necessitate the use of adjuvant therapy. However, most positive margins are identified postoperatively as deep margins, and intraoperative identification of the deep positive margins could help achieve adequate surgical margins and decrease adjuvant therapies. To improve deep-margin identification, we investigated whether the use of high-resolution preclinical PET and CT could increase certainty about the surgical margins in three dimensions. Patients with a malignancy of the head and neck planned for surgical resection were administered a clinical activity of 4MBq/kg ¹⁸F-FDG approximately one hour prior to surgical initiation. Subsequently, the resected specimen was scanned with a micro-PET-CT imaging device, followed by histopathological assessment. Eight patients were included in the study and intraoperative PET/CT-imaging of 11 tumoral specimens and lymph nodes of three patients was performed. As a result of the increased resolution, differentiation between inflamed and dysplastic tissue versus malignant tissue was complicated in malignancies with increased peritumoral inflammation. The current technique allowed the three-dimensional delineation of ¹⁸F-FDG using submillimetric PET/CT imaging. While further optimization and patient stratification is required, clinical implementation could enable deep margin assessment in head and neck resection specimens. Full article

Bariatric surgery is an emerging therapeutic approach for obese type 2 diabetes mellitus (T2DM) patients, with proven benefits for achieving target glucose control and even remission of diabetes. However, the effect of bariatric surgery upon diabetic retinopathy is still a subject of debate as some studies show a positive effect while others raise concerns about potential early worsening effects. We performed a systematic review, on PubMed, Science Direct, and Web of Science databases regarding the onset and progression of diabetic retinopathy in obese T2DM patients who underwent weight-loss surgical procedures. A total of 6375 T2DM patients were analyzed. Most cases remained stable after bariatric surgery (89.6%). New onset of diabetic retinopathy (DR) was documented in 290 out of 5972 patients (4.8%). In cases with DR at baseline, progression was documented in 50 out of 403 (12.4%) and regression in 90 (22.3%). Preoperative careful preparation of hemoglobin A1c (HbA1c), blood pressure, and lipidemia should be provided to minimize the expectation of DR worsening. Ophthalmologic follow-up should be continued regularly in the postoperative period even in the case of diabetic remission. Further randomized trials are needed to better understand the organ-specific risk factors for progression and provide personalized counseling for T2DM patients planned for bariatric surgery. Full article

Chronic lymphocytic leukemia (CLL) is highly heterogeneous, with extremely variable clinical course. The clinical heterogeneity of CLL reflects differences in the biology of the disease, including chromosomal alterations, specific immunophenotypic patterns and serum markers. The application of next-generation sequencing techniques has demonstrated the high genetic and epigenetic heterogeneity in CLL. The novel mutations could be pharmacologically targeted for individualized approach in some of the CLL patients. Potential neurogenic locus notch homolog protein 1 (NOTCH1) signalling targeting mechanisms in CLL include secretase inhibitors and specific antibodies to block NOTCH ligand/receptor interactions. In vitro studies characterizing the effect of the splicing inhibitors resulted in increased apoptosis of CLL cells regardless of splicing factor 3B subunit 1 (SF3B1) status. Several therapeutic strategies have been also proposed to directly or indirectly inhibit the toll-like receptor/myeloid differentiation primary response gene 88 (TLR/MyD88) pathway. Another potential approach is targeting nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and inhibition of this prosurvival pathway. Newly discovered mutations and their signalling pathways play key roles in the course of the disease. This opens new opportunities in the management and treatment of CLL. Full article

Purpose: Detection of cardiac involvement in Fabry disease (FD) is of high importance for treatment management. Native T1 mapping especially showed great potential for detection of early cardiac manifestations. Echocardiographic studies showed strain abnormalities in FD patients, but data on MRI feature tracking strain analysis (FT-SA) is limited. Therefore, the aim of our study was to evaluate the potential of FT-SA compared to native T1 and the FD specific biomarker Globotriaosylsphingosine (LysoGb3). Methods: 28 consecutive FD patients (18 female; 47.8 years ± 17.4 standard deviation (SD)) and 28 control subjects (18 female; 46.6 years ± 18.2 SD) underwent cardiac MRI at 1.5 Tesla. Global native T1 times and left ventricular FT-SA were evaluated. Results were correlated to serum Lyso-Gb3-levels. Results: Native T1 times, global longitudinal (GLS) and global radial strain (GRS) were significantly reduced in FD patients (p < 0.0064, p = 0.0009 and p = 0.0184, respectively). Moreover, native T1 times and GLS were significantly lower in Lyso-Gb3 positive FD patients (p < 0.005 and p = 0.03). GLS, native T1 times showed significant moderate correlations to LysoGb3 (p = 0.002 and p < 0.001). Furthermore, GLS and native T1 times reduce when LysoGb3 was elevated and increasingly with presence of left ventricular hypertrophy (LVH) or late gadolinium enhancement (LGE). Conclusions: Native T1 times and strain values differ significantly between FD patients and control subjects and showed promising correlations to the FD specific biomarker LysoGb3. We therefore conclude that strain abnormalities occur early beside native T1 reductions in cardiac FD involvement. Large scale trials are needed to verify our findings. Full article

Growth hormone (GH) is involved in the regulation of the postnatal dental and skeletal growth, but its effects on oral health have not been clearly defined. This paper aims to provide a review of current clinical knowledge of dental caries, tooth wear, developmental enamel defects, craniofacial growth and morphology, dental maturation, and tooth eruption in growth hormone deficient (GHD) children. A systematic review was carried out using Scopus, MEDLINE-EbscoHost and Web of Science from 2000 to May 2021. PRISMA guidelines for reporting systematic reviews were followed. All the selected studies involved groups under eighteen years of age, covering a total of 465 GHD patients. The studies that were selected provide reliable evidence for delayed dental maturity and orthodontic disturbances in GHD patients. Data on dental hard tissues pathology are scarce and are limited to occurrences of dental caries. GHD children showed abnormal craniofacial morphology with reduced mandibular dimensions, with a resulting tendency towards Angle’s Class II occlusion, which affected up to 31% of patients. Dental age has been shown to be delayed in GHD patients by about 1 to 2 years. Moreover, the risk of dental caries in children with GHD decreases with increasing levels of vitamin D. Hence, further studies would be valuable for evaluating the risk of various oral health problems and to organize targeted dental care for this vulnerable group. Full article

Background/aims: Anemia of chronic disease is a common feature in diabetes and chronic kidney disease. Hepcidin is the key element involved in iron metabolism; however, studies on new indices of iron status are still ongoing. The aim of the study was to assess novel iron parameters in patients with type 2 diabetes mellitus in relation to kidney function. Methods: The study included 80 type 2 diabetic patients and 23 healthy volunteers. Standard laboratory measurements were used to measure the iron status, complete blood count, creatinine, the estimated glomerular filtration rate (eGFR), serum lipids, and brain natriuretic peptides (BNPs). Commercially available kits were used to measure hepcidin-25, the soluble transferrin receptor (sTfR), growth differentiation factor-15 (GDF-15), and hypoxia-inducible factor-1 alpha. Results: Anemia was present in 65% of the studied patients. The control group was found to have significantly higher hepcidin, sTfR, and GDF-15, and lower hemoglobin and iron. When compared with patients with eGFR values ≥60 mL/min/1.73 m² and <60 mL/min/1.73 m², we found that patients with higher eGFR had higher hemoglobin, ferritin, and HIF-1 alpha, lower BNP, and were younger. We found that levels of HIF-1 alpha are negligible in the studied population and were related to age only in patients with eGFR values ≥60 mL/min/1.73 m². Conclusion: A comprehensive assessment of iron status is rarely performed. Novel biomarkers of iron metabolism are not generally related to kidney function. Whether the assessment of HIF-1 alpha would be a marker of efficient anemia therapy with HIF-prolyl hydroxylase inhibitors is still a matter for further study. Full article

There is insufficient evidence about the cardioprotective effects of statins against chemotherapy-induced cardiomyopathy. The MEDLINE and EMBASE databases were searched from inception to March 2021 for studies that reported the mean left ventricular ejection fraction (LVEF) before and after chemotherapy and the incidence of chemotherapy-induced cardiotoxicity in patients who received concurrent statin therapy and those who received chemotherapy alone. A random effects meta-analysis was performed to obtain the pooled weighted mean difference (WMD) and the 95% confidence interval (CI) for the mean final LVEF and the mean LVEF change, and the pooled odds ratio (OR) and the 95% CI of the incidence of chemotherapy-induced cardiomyopathy. Seven studies with 3042 patients were included in this meta-analysis (statin group: 1382 patients received concurrent statin with chemotherapy; control group: 1660 patients received chemotherapy alone). Patients in the control group had a more significant decline in LVEF (WMD = −6.08%, 95% CI: −8.55 to −3.61, p < 0.001) compared to those in the statin group. Additionally, the statin group had a significantly lower incidence of chemotherapy-induced cardiomyopathy compared to the control group (OR = 0.41, 95% CI = 0.28–0.60, p < 0.001). Consequently, our study showed a significant reduction in the incidence of chemotherapy-induced cardiomyopathy and the degree of LVEF decline in patients in the statin group compared to those in the control group. Full article