J. Clin. Med., Volume 9, Issue 11 (November 2020) – 409 articles

Purpose: To determine the association between tear film thickness (TFT) as measured with ultra-high resolution optical coherence tomography (UHR-OCT) and signs and symptoms of dry eye disease (DED). Methods: A total of 450 eyes from 225 patients with DED from six different randomized clinical trials were included in this pooled analysis. In all subjects, TFT was measured with a custom-built UHR-OCT system. Symptoms of DED were quantified using a standardized Ocular Surface Disease Index (OSD)I questionnaire and clinical signs including tear film break up time (TFBUT) and Schirmer I test were assessed. Associations of the average TFT with OSDI, TFBUT, and Schirmer I test were calculated using a linear regression analysis. Results: The average TFT of the included sample (mean age, 45.0 ± 13.3 years; 65% female) was 4.2 ± 0.5 µm and the OSDI 36.2 ± 10.4. A significant negative correlation was found between TFT and OSDI (r = −0.36 to −0.31; p < 0.001). Tear break up time and Schirmer I test were not correlated with OSDI. Significant albeit weak correlations were found between TFT and TFBUT (r = 0.17 to 0.25; p < 0.01) as well as Schirmer I (r = 0.36 to 0.37; p < 0.001). Subgroup analysis revealed that the correlation was stronger in the subjects with abnormal Schirmer I (<15 mm; r = 0.50 to 0.54; p < 0.001). Conclusions: The present study demonstrates an objective measurement of TFT using a novel OCT approach for DED that correlates with symptoms and signs of DED. Our data are consistent with the idea that TFT represents the aqueous-deficient component of DED. Full article

Gitelman syndrome (GS) is a rare salt-losing tubulopathy caused by an inactivating mutation in the SLC12A3 gene, encoding the thiazide-sensitive sodium chloride cotransporter (NCC). Patients with GS frequently complain of vertigo, usually attributed to hypovolemia. Because NCC is also located in the endolymphatic sac, we hypothesized that patients with GS might have vestibular dysfunction. Between April 2013 and September 2016, 20 (22%) out of 90 patients followed at the reference center complained of vertigo in the absence of orthostatic hypotension. Sixteen of them were referred to an otology department for investigation of vestibular function. The vertigo was of short duration and triggered in half of them by head rotation. Seven patients (44%) had a vestibular syndrome. Vestibular syndrome was defined: (1) clinically, as nystagmus triggered by the head shaking test (n = 5); and/or (2) paraclinically, as an abnormal video head impulse test (n = 0), abnormal kinetic test (n = 4) and/or abnormal bithermal caloric test (n = 3). Five patients had associated auditory signs (tinnitus, aural fullness or hearing loss). In conclusion, we found a high frequency of vestibular disorder in GS patients suffering from vertigo, suggesting a role of NCC in the inner ear. Referent physicians of these patients should be aware of this extrarenal manifestation that requires specific investigations and treatment. Full article

The aim of this study was to evaluate changes in the use of fresh-frozen plasma (FFP) transfusions and the use of clotting tests in preterm neonates in our center over the past two decades. In this retrospective cohort analysis, we included all consecutive neonates with a gestational age at birth between 24 + 0 and 31 + 6 weeks admitted to our neonatal intensive care unit (NICU) between 2004 and 2019. We divided all included neonates into three consecutive time epochs according to date of birth: January 2004 to April 2009, May 2009 to August 2014 and September 2014 to December 2019. The main outcomes were the use of FFP transfusion, coagulation testing and the indications for FFP transfusion. The percentage of preterm neonates receiving FFP transfusion decreased from 5.7% (47/824) to 3.7% (30/901) to 2.0% (17/852) from the first epoch to the last epoch (p < 0.001). Additionally, the rate of neonates undergoing coagulation testing decreased from 24.3% (200/824) to 14.5% (131/901) to 8% (68/852) over the epochs (p < 0.001). Most FFP transfusions were prescribed prophylactically based on prolongation of activated partial thromboplastin time (aPTT) or prothrombin time (PT) (56%). In conclusion, both the use of FFP transfusions and the use of coagulation tests decreased significantly over the years. The majority of the FFP transfusions were administrated prophylactically for abnormal coagulation tests. Full article

There is a growing trend of using energy drinks and caffeinated beverages to improve cognitive performance that is widespread and well-studied among children and teenagers with Attention Deficit Hyperactive Disorder (ADHD), but little is known about adult ADHD (A-ADHD). As a consequence, the use of highly caffeinated drinks and their impact on ADHD symptoms are poorly understood. This is especially true in populations where A-ADHD and the use of these beverages are largely represented, such as in military samples. From the All Army Study (AAS) of the Army Study to Assess Risk and Resilience in Service members (STARRS) data, 1,239 A-ADHD soldiers and 17,674 peers without any psychiatric comorbidity were selected. The two groups were compared on: (1) the presence of substance use disorder (SUD) diagnosis both over their lifetime and in the previous 30 days; (2) patterns of alcohol and caffeine use using chi-square analyses. Lastly, the relationship between substance use and severity of A-ADHD symptoms was assessed using Pearson’s correlations. Soldiers with a diagnosis of A-ADHD had a higher prevalence of SUD diagnosis compared to their peers without psychiatric comorbidity. They also tended to use more alcohol, caffeine pills, energy drinks, and other caffeinated drinks. Alcohol use was positively correlated with A-ADHD symptoms; on the contrary, energy drinks, caffeine pills and other caffeinated drinks showed negative correlations with some aspects of A-ADHD symptomatology. The use of caffeinated compounds appears to be increased among military soldiers with ADHD, and they may help reducing A-ADHD symptoms and improve cognitive performance. These results suggest a possible role for caffeine as a potential pharmacological tool in the treatment of adult ADHD. Full article

Most studies on well-being during the COVID-19 pandemic have focused on the mental health of the general population; far less attention has been given to more specific populations, such as patients with mental illness. Indeed, it is important to examine the psychiatric population, given its vulnerability. The present study aimed at assessing the psychological and emotional impact of isolation on patients in Residential Rehabilitation Communities, compared to healthy controls. A questionnaire was administered cross-sectionally on an online survey platform and both psychiatric patients and healthy controls accessed via a designed link. The results showed significant differences between psychiatric patients and controls on Anxiety, Stress, Worry, and Risk Perception variables. Psychiatric patients scored lower on Stress compared to healthy controls and higher on Anxiety, Perceived Risk of getting infected with COVID-19 and Worry about the emergency situation. The results showed that, during the Italian lockdown, psychiatric patients living in residential communities received unbroken support from peers and mental health professionals, maintained their usual medication treatment, and were informed of COVID-19 consequences. This finding provides insight into the differences between residential and healthy populations and highlights the importance of continuous support for psychiatric patients, especially during stressful situations such as a pandemic. Full article

Background: There have been several pathologic data that support an association between postural instability (PI) and autonomic dysfunction in Parkinson’s disease (PD). The purpose of this study was to investigate the correlation of PI and autonomic deficits in early PD. Methods: We collected 17 patients with a diagnosis of early PD. PI was assessed by computerized dynamic posturography (CDP). Standardized autonomic function test (AFT) and time and frequency domain spectral analysis of heart rate variability (HRV) were performed. CDP data obtained from the 21 patients were compared to that from age- and sex-matched healthy controls. We collected HRV data from 18 other age- and sex-matched controls. All patients were evaluated in the “OFF” state. We used Mann–Whitney U-test to compare parameters of CDP between the early PD and control groups. Spearman correlation was used for correlation analysis between parameters of CDP and autonomic function test in PD patients. Results: Most patients (76.5%) showed mild or moderate autonomic dysfunction in the standardized AFT. In CDP, sensory ratios of equilibrium score (e.g., visual and vestibular) and composite scores were significantly lower in PD patients than in controls. In HRV, the low-frequency/high-frequency ratio during the tilt and the gap of low- frequency/high-frequency ratio from supine to tilt were significantly different in both groups. The parameters of time and frequency domains of HRV reflecting parasympathetic function were correlated with equilibrium scores for somatosensory organization test in CDP. Discussion: PI was associated with parasympathetic autonomic dysfunction in early PD. This result was in accordance with a previous assumption that PI in PD is related to parasympathetic cholinergic neuron loss in the brainstem. Full article

The receptor for advanced glycation end products (RAGE), a well-known player of diabetes mellitus (DM)-related morbidities, was supposed to be involved in coronavirus disease-19 (COVID-19), but no data exist about COVID-19, DM, and the soluble RAGE (sRAGE) forms. We quantified total sRAGE and its forms, the endogenously secretory esRAGE and the membrane-cleaved cRAGE, in COVID-19 patients with and without DM and in healthy individuals to explore how COVID-19 may affect these molecules and their potential role as biomarkers. Circulating sRAGE and esRAGE were quantified by enzyme-linked-immunosorbent assays. cRAGE was obtained by subtracting esRAGE from total sRAGE. sRAGE, esRAGE, cRAGE, and the cRAGE/esRAGE ratio did not differ between DM and non-DM patients and had the same trend when compared to healthy individuals. Levels of total sRAGE, cRAGE, and cRAGE/esRAGE ratio were upregulated, while esRAGE was downregulated. The lack of difference between DM and non-DM COVID-19 patients in the levels of sRAGE and its forms supports the hypothesis that in COVID-19 the RAGE system is modulated regardless of glycemic control. Identifying how sRAGE and its forms associate to COVID-19 prognosis and the potential of RAGE as a therapeutic target to control inflammatory burden seem of relevance to help treatment of COVID-19. Full article

Transjugular intrahepatic portosystemic shunt (TIPS) is an established treatment tool in decompensated liver cirrhosis that has been shown to prolong transplant-free survival. Hepatic encephalopathy (HE) is a frequent complication of decompensated cirrhosis, eventually induced and/or aggravated by TIPS, that remains a clinical challenge especially in these patients. Therefore, patient selection for TIPS requires careful assessment of risk factors for HE. TIPS procedural parameters regarding stent size and invasive portosystemic pressure gradient measurements thereby have an important role. Endovascular shunt modification, in combination with a conservative medical approach, often results in a significant reduction of symptoms. This review summarizes HE molecular mechanisms and pathophysiology as well as diagnostic and therapeutic approaches targeting shunt-induced HE. Full article

Psychosocial stress increases cardiovascular risk, which coincides with enhanced oxidative DNA damage. Increased sympathetic tone-related catecholamine release causes oxidative stress, which contributes to catecholamine-related cardiotoxicity. Therefore, we tested the hypothesis whether acute psychosocial stress induces oxidative DNA damage, its degree being related to the cardiovascular risk profile and depending on the sympathetic stress response. After assessment of the prospective cardiovascular Münster score (PROCAM) to determine the risk of acute myocardial infarction, 83 male and 12 female healthy volunteers underwent the Trier social stress test for groups (TSST-G). Heart rate variability was quantified by measuring the standard deviation (SDNN) and root mean square of successive differences (RMSSD) between normal-to-normal inter-beat intervals. Salivary α-amylase (sAA) activity was assessed as a surrogate for noradrenaline plasma concentrations. Oxidative DNA damage was determined using whole-blood single-cell gel electrophoresis (“tail moment” in the “comet assay”). A total of 33 subjects presented with a prospective risk of myocardial infarction (risk+) vs. 59 subjects without risk (risk-). The TSST-G stress significantly increased blood pressure, heart rate, and sAA in both groups, while oxidative DNA damage was only increased in the risk+ group. Immediately after the TSST-G, the “tail moment” showed significant inverse linear relations with both SDNN and RMSSD. Acute psychosocial stress may cause oxidative DNA damage, the degree of which is directly related to the individual cardiovascular risk profile and depends on the stress-induced increase in the sympathetic tone. Full article

Fetal hemoglobin (HbF) usually consists of 4 to 10% of total hemoglobin in adults of African descent with sickle cell anemia. Rarely, their HbF levels reach more than 30%. High HbF levels are sometimes a result of β-globin gene deletions or point mutations in the promoters of the HbF genes. Collectively, the phenotype caused by these mutations is called hereditary persistence of fetal hemoglobin, or HPFH. The pancellularity of HbF associated with these mutations inhibits sickle hemoglobin polymerization in most sickle erythrocytes so that these patients usually have inconsequential hemolysis and few, if any, vasoocclusive complications. Unusually high HbF can also be associated with variants of the major repressors of the HbF genes, BCL11A and MYB. Perhaps most often, we lack an explanation for very high HbF levels in sickle cell anemia. Full article

Arrhythmogenic cardiomyopathy (ACM) is primarily a familial disease with autosomal dominant inheritance. Incomplete penetrance and variable expression are common, resulting in diverse clinical manifestations. Although recent studies on genotype–phenotype relationships have improved our understanding of the molecular mechanisms leading to the expression of the full-blown disease, the underlying genetic substrate and the clinical course of asymptomatic or oligo-symptomatic mutation carriers are still poorly understood. We aimed to analyze different phenotypic expression profiles of ACM in the context of the same familial genetic mutation by studying nine adult cases from four different families with four different familial variants (two plakophilin-2 and two desmoglein-2) from the Swiss Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) Registry. The affected individuals with the same genetic variants presented with highly variable phenotypes ranging from no disease or a classical, right-sided disease, to ACM with biventricular presentation. Moreover, some patients developed early-onset, electrically unstable disease whereas others with the same genetic variants presented with late-onset electrically stable disease. Despite differences in age, gender, underlying genotype, and other clinical characteristics, physical exercise has been observed as the common denominator in provoking an arrhythmic phenotype in these families. Full article

Low skeletal muscle mass (LSMM) is increasingly recognized for its predictive value for adverse events in cancer patients. In specific, the predictive value of LSMM has been demonstrated for anti-cancer drug toxicity in a variety of cancer types and anti-cancer drugs. However, due to the limited sample size and study populations focused on a single cancer type, an overall predictive value of LSMM for anti-cancer drug toxicity remains unknown. Therefore, this review aims to provide a comprehensive overview of the predictive value of LSMM and perform a meta-analysis to analyse the overall effect. A systematic search was conducted of MEDLINE, Scopus, EMBASE, and Cochrane. Inclusion criteria were skeletal muscle mass (SMM) evaluated with computed tomography (CT) or magnetic resonance imaging (MRI), articles published in English, SMM studied in humans, SMM measurement normalized for height, and patients did not receive an intervention to treat or prevent LSMM. A meta-analysis was performed using a random-effects model and expressed in odds ratio (OR) with 95% confidence interval (CI). Heterogeneity was assessed using χ² and I² statistics. The search yielded 907 studies. 31 studies were included in the systematic review. Sample sizes ranged from 21 to 414 patients. The occurrence of LSMM ranged from 12.2% to 89.0%. The most frequently studied cancer types were oesophageal, renal, colorectal, breast, and head and neck cancer. Patients with LSMM had a higher risk of severe toxicity (OR 4.08; 95% CI 2.48–6.70; p < 0.001) and dose-limiting toxicity (OR 2.24; 95% CI 1.28–3.92; p < 0.001) compared to patients without LSMM. To conclude, the predictive value of LSMM for anti-cancer drug toxicity can be observed across cancer types. This information increases the need for further research into interventions that could treat LSMM as well as the possibility to adapt treatment regimens based on the presence of LSMM. Full article

Patients with type 2 diabetes (T2DM) are at high risk of developing cardiovascular disease and heart failure (HF), both with preserved and reduced ejection fraction of the left ventricle. Previous research demonstrated that dapagliflozin treatment is associated with the remission of type 1 diastolic dysfunction (DD1) in patients with T2DM. The main aim of this study was to evaluate the possible baseline predictors associated with the remission of DD1 in patients with T2D after one year of dapagliflozin treatment. In this prospective and observational study, 45 patients with T2DM were evaluated before and after one year of treatment with 10 mg dapagliflozin daily added to their background therapy. In the studied group, 73.3% (33/45) of the patients had DD1 at baseline. The primary outcome of this research was DD1 remission. DD1 remission was associated with improvement of liver stiffness, an increase in estimated glomerular filtration rate (eGFR), and a decrease in hemoglobin A1c (HbA1c). Independent predictors for the remission of DD1 were a more than 0.4 kPa difference in the initial stiffness score and the 1-year assessment fibrosis score and a duration of diabetes ≤8 years. Age, body mass index (BMI), or patient weight after one year did not influence the DD1 outcome. Patients with a T2DM duration of less than eight years have the additional benefit of DD1 remission associated with dapagliflozin treatment beyond the conventional benefits such as improvements in glycemic control, cardiovascular, renal, and hepatic risk reductions. In patients with T2DM, the remission of DD1 was associated with decrease of liver stiffness. Full article

Background: Autologous stem cell transplantation (ASCT) remains an effective treatment option for many patients with systemic light chain (AL) amyloidosis. While maintenance post ASCT in multiple myeloma is now standard, the decision to utilize maintenance in AL amyloidosis remains largely unexplored. The present study aims to determine the prognostic significance of utilizing maintenance therapy following ASCT and assess the impact of fluorescent in situ hybridization (FISH) abnormalities, bone marrow plasma cell burden (BMPC), and degree of organ involvement on this decision. Methods and results: This is a retrospective analysis of fifty AL amyloidosis patients who underwent ASCT at The Ohio State University. Twenty-eight patients received maintenance and twenty-two did not. Kaplan–Meier survival analysis was used to compare the effect of maintenance therapy with no significant difference in PFS (p = 0.66) and OS (p = 0.32) between the two groups. There was no difference in survival based on maintenance when further categorized by FISH, PFS (p = 0.15), and OS (p = 0.65); BMPC ≥ 10%, PFS (p = 0.49), and OS (p = 0.32); or with 2 or more organs involved, PFS (p = 0.34) and OS (p = 0.80). Conclusion: Maintenance therapy post ASCT did not impact PFS or OS when categorized by FISH abnormalities, increasing BMPC, or ≥2 organs involved in AL amyloidosis patients. Full article

Development of novel antiviral molecules from the beginning costs an average of $350 million to $2 billion per drug, and the journey from the laboratory to the clinic takes about 10–15 years. Utilization of drug repurposing approaches has generated substantial interest in order to overcome these drawbacks. A drastic reduction in the failure rate, which otherwise is ~92%, is achieved with the drug repurposing approach. The recent exploration of the drug repurposing approach to combat the COVID-19 pandemic has further validated the fact that it is more beneficial to reinvestigate the in-practice drugs for a new application instead of designing novel drugs. The first successful example of drug repurposing is zidovudine (AZT), which was developed as an anti-cancer agent in the 1960s and was later approved by the US FDA as an anti-HIV therapeutic drug in the late 1980s after fast track clinical trials. Since that time, the drug repurposing approach has been successfully utilized to develop effective therapeutic strategies against a plethora of diseases. Hence, an extensive application of the drug repurposing approach will not only help to fight the current pandemics more efficiently but also predict and prepare for newly emerging viral infections. In this review, we discuss in detail the drug repurposing approach and its advancements related to viral infections such as Human Immunodeficiency Virus (HIV) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Full article

This study aimed to determine diagnostic and prognostic differences in major forms of interstitial lung disease using quantitative CT imaging. A retrospective study of 225 subjects with a multidisciplinary diagnosis of idiopathic pulmonary fibrosis (IPF), interstitial pneumonia with autoimmune features (IPAF), connective tissue disease (CTD), or chronic hypersensitivity pneumonitis (cHP) was conducted. Non-contrast CT scans were analyzed using the Computer Aided Lung Informatics for Pathology Evaluation and Rating (CALIPER) program. Resulting data were analyzed statistically using ANOVA and Student’s t-test. Univariate, multivariable, and receiver operating characteristic analyses were conducted on patient mortality data. CALIPER analysis of axial distribution on CT scans in those with IPF demonstrated greater peripheral volumes of reticulation than either CTD (p = 0.033) or cHP (p = 0.007). CTD showed lower peripheral ground-glass opacity than IPF (p = 0.005) and IPAF (p = 0.004). Statistical analysis of zonal distributions revealed reduced lower zone ground-glass opacity in cHP than IPF (p = 0.044) or IPAF (p = 0.018). Analysis of pulmonary vascular-related structure (VRS) volume by diagnosis indicated greater VRS volume in IPF compared to CTD (p = 0.003) and cHP (p = 0.003) as well as in IPAF compared to CTD (p = 0.007) and cHP (p = 0.007). Increased reticulation (p = 0.043) and ground glass opacity (p = 0.032) were predictive of mortality on univariate analysis. Increased pulmonary VRS volume was predictive of mortality (p < 0.001) even after multivariate analysis (p = 0.041). Quantitative CT imaging revealed significant differences between ILD diagnoses in specific CT findings in axial and, to a lesser degree, zonal distributions. Increased pulmonary VRS volume seems to be associated with both diagnosis and survival. Full article

This study aimed to test the effectiveness of a solution of chlorhexidine (CHX) and D-α-tocopheryl polyethylene glycol succinate (Vitamin E TPGS or TPGS) in the treatment of Acanthamoeba keratitis (AK) via a prospective, interventional case series study. Twenty-nine consecutive patients with AK were enrolled. At baseline, best-corrected visual acuity (BCVA), slit lamp examination, confocal microscopy, and polymerase chain reaction (PCR) were performed. Topical therapy with CHX 0.02% and VE-TPGS 0.2% was administered hourly/24 h for the first day, hourly in the daytime for the next three days, and finally, every two hours in the daytime up to one month. BCVA and ocular inflammation were recorded after two weeks, four weeks, and three months from baseline. Mean logMAR BCVA significantly improved at two weeks (0.78) compared to baseline (1.76), remaining stable over time (0.80 at four weeks, 0.77 at three months). Ocular inflammation improved in 14 eyes at 2 weeks, with further slow improvements in all cases. At three months, no patient had signs of corneal inflammation. The presence of corneal scars was first recorded at the two-week follow-up, with an enlargement at the four-week follow-up. At the three-month follow-up, 19 eyes still showed corneal opacities. In conclusion, the tested solution was shown to be effective for the treatment of AK. Furthermore, it might represent a good first-line treatment. Full article

Background: The aim of this study was to identify clinical risk factors for increased post-void residual (PVR) volumes in patients undergoing vaginal prolapse surgery and to find out whether uterus preservation or prolapse hysterectomy influences the incidence of postoperative urinary retention. Methods: This retrospective study included women who presented with pelvic organ prolapse (POP) and planned prolapse surgery between January 2017 and July 2019. PVR was assessed postoperatively and increased amounts were defined as incomplete voiding with residual urine volume greater than 150 mL. Results: Increased PVR at the first postoperative day occurred in 31.8% (56/176). Body mass index (BMI) was significantly lower in patients with increased PVR after pelvic floor surgery compared to patients with normal PVR amounts (p = 0.040). Furthermore, during multiple logistic regression analysis, low BMI (p = 0.009) as well as prolapse hysterectomy (p = 0.032) turned out to be the strongest risk factors associated with increased PVR volume. Conclusion: This is the first study identifying prolapse hysterectomy as an independent risk factor for increased PVR after surgical prolapse repair. Our results might be helpful in counseling patients prior to surgery and underline the option of uterus preservation during prolapse surgery in selected cases. Full article

Objective: To investigate the effects of intravitreal bevacizumab (IVB) injection before PRP on the prevention of macular edema (ME) in patients with PDR. Methods: This retrospective observational study included patients diagnosed with PDR treated by PRP with (combination group) or without (PRP alone group) preoperative IVB injection (1.25 mg/0.05 mL). The primary outcome measure was the change in the central macular thickness (CMT), while the secondary outcome measure was the change in visual acuity. Measurements were made before and at one, two, and three months after treatment. Results: In the PRP alone group, the mean baseline CMT of 277.8 μm increased to 290.4 μm at one month (p = 0.201) and 308.8 μm at two months (p = 0.002), followed by a decrease to 271.2 μm at three months (p = 0.437). In the combination group, the values at baseline and one, two, and three months after PRP were 322.9 μm, 295.4 μm (p = 0.002), 330.1 μm (p = 0.906), and 274.5 μm (p = 0.030), respectively. Visual acuity changes were comparable between the two groups at all time points. Conclusion: IVB injection before PRP leads to decreased CMT in comparison to CMT in patients with PRP alone. Full article

Balance impairment is a frequent disorder in patients with fibromyalgia (FMS), increasing the risk of falls and decreasing physical function and quality of life. In recent years, the use of active therapy-based training (ATBT) has increased, with the aim of improving balance in women with FMS. Our study aimed to assess the effect of ATBT to improve different balance outcomes in subjects with FMS. A systematic review with meta-analysis was carried out. We searched PubMed Medline, SCOPUS, Web of Science, CINAHL, and PEDro (Physiotherapy Evidence Database) databases up to September 2020. We included randomized controlled trials (RCT) that assessed the balance in patients with FMS after ATBT and compared to other treatments or no intervention. In a random-effects model, the standardized mean difference (SMD) was used to calculate the effect size. Ten studies were included in the review providing data from 546 FMS patients with a mean age of 52.41 ± 2.90 years old (98% females). Our results showed a medium effect favors ATBT with respect to other therapies for monopedal static balance (SMD = 0.571; 95% CI = 0.305, 0.836; p < 0.001), dynamic balance (SMD = 0.618; 95% CI = 0.348, 0.888; p < 0.001), and functional balance (SMD = 0.409; 95% CI = 0.044, 0.774; p = 0.028). No statistically significant differences were found for balance on unstable support. The present meta-analysis showed moderate-quality evidence of a medium effect of ATBT to improve dynamic and functional balance and low-quality evidence of a medium effect to improve monopedal static balance with respect to other therapies or no intervention. Full article

Because of limitations caused by unique complications of free flap reconstruction, the Clavien–Dindo classification was modified to include grade “IIIc” for “partial or total free flap failure.” From 2013 to 2018, 116 patients who had undergone free flap reconstruction for head and neck cancer with grade III or higher postoperative complications were grouped using the “Modified” Clavien–Dindo classification. Alcoholism displayed significant predictive effects between grade IIIb and IIIc (72.7% vs. 50%, p = 0.028). Significant differences were observed between grade IIIb and IIIc in the duration of hospital stay (23.1 ± 10.1 vs. 28.6 ± 11.9 days, p = 0.015), duration of intensive care unit stay (6.0 ± 3.4 vs. 8.7 ± 4.3 days, p = 0.001), reoperation times during the current hospitalization (1.4 ± 0.8 vs. 2.0 ± 1.0 times, p < 0.001), and wound infection rate (29.9% vs. 62.5%, p = 0.002). The severity levels were significantly positively correlated with reoperation times during the current hospitalization (p < 0.001), ICU stay (p = 0.001), and hospital stay (p < 0.001). The modified Clavien–Dindo classification with grade IIIc describes the perioperative complications of head and neck free flap reconstruction to predict clinical outcomes based on severity. Full article

While cardiovascular disease has been associated with an increased risk of coronavirus disease 2019 (COVID-19), no studies have described its clinical course in patients with aortic stenosis who had undergone transcatheter aortic valve replacement (TAVR). Numerous observational studies have reported an association between the A blood group and an increased susceptibility to SARS-CoV-2 infection. Our objective was to investigate the frequency and clinical course of COVID-19 in a large sample of patients who had undergone TAVR and to determine the associations of the ABO blood group with disease occurrence and outcomes. Patients who had undergone TAVR between 2010 and 2019 were included in this study and followed-up through the recent COVID-19 outbreak. The occurrence and severity (hospitalization and/or death) of COVID-19 and their associations with the ABO blood group served as the main outcome measures. Of the 1125 patients who had undergone TAVR, 403 (36%) died before 1 January 2020, and 20 (1.8%) were lost to follow-up. The study sample therefore consisted of 702 patients. Of them, we identified 22 cases (3.1%) with COVID-19. Fourteen patients (63.6%) were hospitalized or died of disease. Multivariable analysis identified the A blood group (vs. others) as the only independent predictor of COVID-19 in patients who had undergone TAVR (odds ratio (OR) = 6.32; 95% confidence interval (CI) = 2.11−18.92; p = 0.001). The A blood group (vs. others; OR = 8.27; 95% CI = 1.83−37.43, p = 0.006) and a history of cancer (OR = 4.99; 95% CI = 1.64−15.27, p = 0.005) were significantly and independently associated with disease severity (hospitalization and/or death). We conclude that patients who have undergone TAVR frequently have a number of cardiovascular comorbidities that may work to increase the risk of COVID-19. The subgroup with the A blood group was especially prone to developing the disease and showed unfavorable outcomes. Full article

The evidence is still unclear regarding the role of blood parameters in detecting complications in patients who suffer from diabetic foot osteomyelitis (DFO). In this study, the aim was to identify the capacity of different blood parameters in the diagnosis and prediction of the onset of complications. A cross-sectional prospective study was carried out with 116 DFO patients. The following blood parameters were evaluated during 1 year of follow-up: leukocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils, erythrocyte sedimentation rate (ESR), glycemia, glycosylated hemoglobin, C-reactive protein (CRP), alkaline phosphatase, albumin, and creatinine. Complication events were assessed for each participant during the study period. We investigated the association between blood parameter values and the onset of complication events by conducting a receiver operating characteristic curve analysis. Eighty-five (73.3%) patients developed complications. Regarding blood parameters, higher values of lymphocytes and albumin were predictive factors at the 12-month follow-up once the ulcer had healed. Higher values of ESR had predictive and diagnostic value for the onset of complication events, and higher values of CRP and hyperglycemia were diagnostic factors since they were elevated during the occurrence of an event. In conclusion, after suffering from DFO, the elevation of lymphocytes, ESR, CRP, albumin, and glycemia could be useful in detecting and diagnosing patients who are likely to develop a complication. Serial blood tests are a useful tool for early detection by healthcare professionals to prevent complications. Full article

People with diabetic peripheral neuropathy (DPN) experience lower quality of life caused by associated balance, posture, and gait impairments. While focal muscle vibration (FMV) has been associated with improvements in gait performance in individuals with neurological disorders, little is known about its effectiveness in patients with DPN. The purpose of this study was to investigate the effect of FMV on gait outcomes in patients with DPN. The authors randomized 23 participants into three FMV intervention groups depending upon the delivery of vibration. Participants applied wearable FMV to the bilateral quadriceps, gastrocnemius, and tibialis anterior, 10 min per muscle, three times per week over a four-week period. Spatiotemporal, kinematic, and kinetic gait parameters at baseline and post-intervention were calculated and analyzed. Gait speed, cadence, stride time, left and right stance time, duration of double limb support, and left and right knee flexor moments significantly improved after four weeks of FMV. Trends toward significant improvements were noted in maximum left and right knee flexion. Results indicate that FMV therapy was associated with improvements in gait parameters in individuals with DPN, warranting expanded study of FMV therapy for long-term gait performance improvement in these individuals. Full article

The involvement of macular preganglionic elements’ function, during the neurodegenerative process of multiple sclerosis (MS), is controversial. In this case-control observational and retrospective study, we assessed multifocal electroretinogram (mfERG) responses from 41 healthy Controls, 41 relapsing-remitting MS patients without optic neuritis (ON) (MS-noON Group) and 47 MS patients with ON: 27 with full recovery of high-contrast best corrected visual acuity (BCVA) (MS-ON-G Group) and 20 with poor recovery (between 0.2 and 1 LogMAR) of BCVA, (MS-ON-P Group). In the latter Group, Sd-OCT macular volumes and thicknesses of whole and inner and outer retina were measured. MfERG N1 and P1 implicit times (ITs), and N1-P1 response amplitude densities (RADs), were measured from concentric rings (R) with increasing foveal eccentricity: 0–5° (R1), 5–10° (R2), 10–15° (R3), 15–20° (R4), 20–25° (R5), and from retinal sectors (superior, nasal, inferior and temporal) between 0–15° and 0–25°. In the MS-ON-P Group, mean mfERG RADs detected from R1 (0–5°) and from the central nasal sector (0–15°) were significantly reduced (p < 0.01) with respect to those of the Control, MS-noON and MS-ON-G Groups. No other significant differences between Groups for any mfERG parameters were found. All Sd-OCT measurements, apart from the inner retina macular volume in the central 1 mm, were significantly reduced in MS-ON-P patients compared to Controls. The functional impairment in the MS-ON-P Group was associated but not correlated with structural changes of the outer and inner retinal layers in corresponding retinal Areas and Sectors. Our results suggest that in MS, exclusively after ON with poor recovery of BCVA, the neurodegenerative process can induce dysfunctional mechanisms involving photoreceptors and bipolar cells of the fovea and of the more central nasal macular area. Full article

Purpose: To investigate the response to gabapentin treatment in patients with dry eye (DE) accompanied by features of neuropathic ocular pain (NOP), and to analyze the differences between clinical manifestations of the groups according to treatment response. Methods: We retrospectively reviewed the records of 35 patients with DE accompanied by NOP features and obtained information on their medical history and previous ocular history. The patients underwent clinical examinations of the tear film, ocular surface, and meibomian gland and completed the Ocular Pain Assessment Survey (OPAS). One month after treatment with topical eye drops, add-on of gabapentin treatment was determined according to the Wong–Baker FACES Pain Rating Scale (WBFPS). A reduction of 2 points or more on the WBFPS was considered a positive treatment response. Enrolled patients were divided into three groups according to the treatment response: topical treatment response group (group 1, n = 11); gabapentin response group (group 2, n = 13); and gabapentin non-response group (group 3, n = 11). The medical history, clinical parameters, and OPAS scores were compared between groups. Results: The incidence of systemic comorbidities was higher in group 2 than in other groups. The corneal staining scores were lower in groups 2 and 3 than in group 1. Among the treatment response groups, group 2 showed improvements in OPAS scores of ocular pain severity, pain other than eyes, and quality of life, while group 1 showed improved OPAS scores of ocular pain severity and ocular associated factors. Group 2 exhibited lower scores of pains aggravated by mechanical and chemical stimuli than group 3. Conclusions: Gabapentin could be effective in patients who have systemic comorbidity and less pain evoked by mechanical and chemical stimuli for the treatment of DE patients with NOP, which is refractory to topical treatment. Full article

Schneiderian membrane perforation (SMP) is the most common complication during sinus floor elevation (SFE). Conventional methods to repair SMP, such as using a collagen barrier, may be clinically demanding. The aim of the present study was to compare the effects of collagenated bone substitute materials with and without a collagen barrier to repair SMP during SFE in terms of new bone formation and dimensional stability. In 12 rabbits, intentional SMP was made during bilateral SFE. The rabbits were randomly assigned under two groups: the control group, in which the sinus was repaired with a collagen barrier, and the test group, in which the sinus was repaired without a collagen barrier. Collagenated bone substitute material was grafted in both groups. Healing periods of 2 weeks and 4 weeks were provided in both groups. There were no adverse clinical events. Histology revealed that the Schneiderian membrane had atrophied with loss of cilia and serous glands in both groups at 4 weeks. Histomorphometry revealed that the newly formed bone (test: 0.42 ± 0.17 mm², control: 0.36 ± 0.18 mm² at 2 weeks; test: 1.21 ± 0.36 mm², control: 1.23 ± 0.55 mm² at 4 weeks) or total augmented area did not significantly differ between the two groups at either time points (p > 0.05). In conclusion, collagenated bone substitute material without a collagen barrier demonstrated similar new bone formation and dimensional stability as that with a collagen barrier in repairing SMP. Full article

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic pulmonary disease with rising incidence. In this study the effectiveness of pirfenidone, as measured by longitudinal change in individual slope of forced vital capacity (FVC) prior to and after initiating pirfenidone treatment, was evaluated in IPF patients recruited into the European registry for idiopathic pulmonary fibrosis (eurIPFreg). Secondary variables were the evaluation of the change in individual slope of diffusion capacity of the lungs for carbon monoxide (DLco), the Borg dyspnea scale, and six-minute walking distance (6MWD), as well as survival analyses. Results: Data of 122 eurIPFreg patients, who had at least two pulmonary function tests (PFTs) prior to or under treatment with pirfenidone, were analyzed by calculating slope-changes. The global analysis revealed an average slope change of +1.48 ± 0.28 (% per annum (p.a)) after start of treatment (p < 0.001), reflecting a reduction in annual FVC decline of approx. 50% under pirfenidone; it also showed a reduction in DLco, and increase in 6MWD (both p < 0.0001), as well as a flattening of the Borg dyspnea scale (p = 0.02). The median survival under treatment was 4.82 years. Patients with a more restrictive disease (FVC < 80% pred.), with a rapid progression (FVC decline >10% pred. p.a.), previous smokers and patients > 60 years of age seemed to profit more from pirfenidone treatment. Conclusions: We report the effectiveness of pirfenidone in a European “real world” IPF cohort with outcome data extending up to 9 years. Global analyses demonstrated a positive effect of pirfenidone on the decline of the lung function over time. Survival was dependent on Gender–Age–Physiology (GAP) score and age prior to therapy. Full article

Obesity increases the risk of developing asthma in children and adults. Obesity is associated with different effects on lung function in children and adults. In adults, obesity has been associated with reduced lung function resulting from a relatively small effect on forced expiratory volume in 1 s (FEV₁) and forced vital capacity (FVC), with the FEV₁/FVC ratio remaining unchanged or mildly increased (restrictive pattern). In contrast, in children, obesity is associated with normal or higher FEV₁ and FVC but a lower FEV₁/FVC ratio (obstructive pattern). This anomaly has recently been associated with a phenomenon known as dysanapsis which results from a disproportionate growth between lung parenchyma size and airway calibre. The mechanisms that promote disproportionate lung parenchyma growth compared with airways in obese children remain to be elucidated. Obesity and dysanapsis in asthma patients might contribute to asthma morbidity by increasing airway obstruction, airway hyper-reactivity and airway inflammation. Obesity and dysanapsis in asthma patients are associated with increased medication use, more emergency department visits, hospitalizations and systemic corticosteroid burst than patients with normal weight. Dysanapsis may explain the reduced response to asthma medications in obese children. Weight loss results in a significant improvement in lung function, airway reactivity and asthma control. Whether these improvements are associated with the changes in the dysanaptic alteration is as yet unclear. Full article