Journal of Clinical Medicine

Background: Providing care can be challenging for informal carers and increases the risk of mental health problems, such as experiencing clinical symptoms of anxiety. While strengthening social support for informal carers is a common recommendation to reduce this risk, no systematic review or meta-analysis to date has examined the relationship between social support and anxiety symptoms in informal carers. The aim of our study was to systematically review the current evidence on the association between perceived and received social support and anxiety symptoms in informal carers of dependent adults and older people, and to comment on the quality of the evidence. Methods: We searched PubMed, CINAHL (EBSCO), PsycINFO (ProQuest), Scopus, and LILACS up to 31 March 2021 for articles reporting on the association between caregiver anxiety symptoms and social support. A random-effects model was used to pool estimates, and each study was rated for quality using pre-specified criteria. Publication bias was assessed using a funnel plot and Egger’s regression test, which was adjusted using trim and fill analysis. Results: From the 2180 identified articles, 35 studies met our inclusion criteria, reporting on 5036 informal carers in total. We found a moderate negative association between perceived social support and caregiver anxiety symptoms (r = −0.31, 95% CI = −0.35, −0.27) and a small, negative association between received social support and caregiver anxiety (r = −0.15, 95% CI = −0.22, −0.08). Conclusion: The levels of perceived social support showed a significant negative association with caregiver anxiety symptoms. Policymakers and those working directly with informal carers should consider the development of targeted social support interventions that specifically enhance the levels of perceived social support to reduce symptoms of anxiety in informal carers. Full article

Post-inflammatory hypopigmentation is a common acquired pigmentary disorder that is more prominent in skin of color, leading to great cosmetic and psychosocial implications. Often, a diagnosis with a pigmentary disorder can negatively impact an individual’s health-related quality of life and may result in stigma. Although most cases of post-inflammatory hypopigmentation resolve spontaneously over time, a systematic diagnostic approach can help with identifying the underlying etiology and informing treatment strategies. It can be due to cutaneous inflammation, sequelae of inflammatory or infectious dermatoses, or dermatologic procedures. Therefore, a thorough understanding of the epidemiology, patient history, physical exam findings, and clinical features of post-inflammatory hypopigmentation phenomenon can explain the primary cause to providers and allow for patient education. It is also important to understand the various therapeutic approaches available and the efficacy of these options, which will inform providers to choose the appropriate therapy for patients. Although algorithms exist for classifying acquired disorders of hypopigmentation, there are no established algorithms for the diagnosis and treatment of post-inflammatory hypopigmentation, which warrants further exploration and discourse. Full article

The prevalence of hypovitaminosis D is increasing worldwide. Vitamin D deficiency is supposed to play a role in sleep disturbances, but the complex relationships between hypovitaminosis D and pediatric obstructive sleep apnea syndrome (OSAS) are still incompletely understood. This study was aimed to retrospectively investigate the vitamin D status and significant clinical, laboratory, and instrumental variables in a cohort of pediatric patients with OSAS and to assess the possible relationship between serum vitamin D levels and OSAS severity. We consecutively enrolled all children aged 2–14 years admitted to our Pediatric Clinic from 1 July 2018 to 30 November 2020 for sleep-disordered breathing. Each patient underwent standard overnight in-hospital polygraphic evaluation, measurement of serum 25-hydroxyvitamin D (25(OH)D) levels, and clinical and laboratory investigation. A total of 127 children with OSAS were included. The 25(OH)D levels and BMI of OSAS patients were compared with those of an age-matched control group: the serum 25(OH)D levels were significantly lower in OSAS patients than in controls (22.4 vs. 25.5 ng/mL; p-value = 0.009), whereas no differences in the BMI percentile were found between the two groups. The mean value of 25(OH)D was not significantly lower (20.9 ng/mL) in the severe OSAS group compared with the mild (23.0 ng/mL) and moderate (23.3 ng/mL) OSAS groups (p-value = 0.28). Our findings indicate a relationship between vitamin D status and OSAS in children and suggest that severe cases of OSAS have lower vitamin D levels. Future, more extensive prospective studies are needed to confirm such preliminary findings. Full article

Background: Some studies have shown that there may be an increase in the frequency of erectile dysfunction after COVID-19. However, no long-term study has investigated whether this is permanent or temporary. In this study, we aimed to examine whether there was an increase in the frequency of erectile dysfunction among individuals with a history of COVID-19, and, if there was, whether their condition improved over time. Materials and methods: In this study, a total of 125 healthy male healthcare workers, 95 with and 30 without a history of COVID-19, were evaluated in terms of erectile function. Four study groups were formed. The first three groups consisted of individuals with a history of COVID-19 confirmed by the polymerase chain reaction (PCR) test at different times, who recovered from the disease (time elapsed since COVID-19 positivity: <6 months for Group 1, 6 to 12 months for Group 2, and >12 months for Group 3). The individuals in Group 4 did not have a history of COVID-19 diagnosis. In order to evaluate the erectile function of the participants, they were asked to complete the five-item International Index of Erectile Function questionnaire (IIEF-5). Then, statistical analyses were performed to evaluate whether there was a difference between the groups in terms of the IIEF-5 scores. Results: There was a statistically significant difference between the groups in terms of the IIEF-5 scores (p < 0.001), and this difference was determined to be caused by the significantly higher IIEF-5 scores of Groups 3 and 4 compared to Group 1 (p = 0.004 and p < 0.001, respectively). In addition, the IIEF-5 score of Group 4 was statistically significantly higher than that of Group 2 (p < 0.001). However, the IIEF-5 scores did not statistically significantly differ between Groups 1 and 2, Groups 2 and 3, and Groups 3 and 4 (p > 0.999, p = 0.204, and p = 0.592, respectively). Conclusion: There may be deterioration in erectile function after COVID-19; however, this tends to improve over time, especially from the first year after active infection. Given that vascular, hormonal, and/or psychogenic factors may lead to the development of erectile dysfunction after COVID-19, we consider that in order to easily manage this process, it is important to determine the underlying cause, initiate appropriate treatment, and inform couples that this situation can be temporary. Full article

Hemodynamic alterations in Fontan patients (FP) are associated with hemostatic dysbalance and Fontan-associated liver disease. Studies of other hepatopathologies indicate an interplay between cholestasis, tissue factor (TF), and von Willebrand factor (VWF). Hence, we hypothesized a relationship between the accumulation of bile acids (BA) and these hemostatic factors in FP. Methods: We included 34 FP (Phenprocoumon n = 15, acetylsalicylic acid (ASA) n = 16). BA were assessed by mass spectrometry. TF activity and VWF antigen (VWF:Ag) were determined by chromogenic assays. VWF collagen-binding activity (VWF:CB) was assessed via ELISA. Results: Cholestasis was observed in 6/34 FP (total BA ≥ 10 µM). BA levels and TF activity did not correlate (p = 0.724). Cholestatic FP had lower platelet counts (p = 0.013) from which 5/6 FP were not treated with ASA. VWF:Ag levels were increased in 9/34 FP and significantly lower in FP receiving ASA (p = 0.044). Acquired von Willebrand syndrome (AVWS) was observed in 10/34-FP, with a higher incidence in cholestatic FP (4/6) (p = 0.048). Conclusions: Cholestasis is unexpectedly infrequent in FP and seems to be less frequent under ASA therapy. Therefore, ASA may reduce the risk of advanced liver fibrosis. FP should be screened for AVWS to avoid bleeding events, especially in cholestatic states. Full article

Liver Transplantation (LT) has become the gold standard treatment for End-Stage Liver Disease (ESLD). One of the main strategies to manage life-threatening complications, such as cardio-respiratory failure, is Extracorporeal Membrane Oxygenation (ECMO) in the peri-transplantation period, with different configurations of the technique and in combination with other extracorporeal care devices such as Continuous Renal Replacement Therapy (CRRT). This retrospective study includes three clinical cases of planned ECMO support strategies in LT and evaluates their application compared with current literature exploring PubMed/Medline. The three LT supported with ECMO and CRRT were performed at IRCCS Polyclinic S. Orsola-Malpighi, Bologna. All three cases of patients with compromised organ function analysed produced positive outcomes. The planned use of ECMO and CRRT support in peri-transplantation has allowed the patients to overcome contraindications and successfully undergo LT. In recent years, only a few reports have documented successful LT outcomes performed with intraoperative ECMO in critically ESLD patients. However, the management of LT with ECMO and/or CRRT assistance is an emerging challenge, with the need for more published evidence on this topic to guide treatment choices in patients with severe, acute and reversible respiratory and cardiovascular failure after LT. Full article

Iterations in stent technologies, advances in pharmacotherapy, and awareness of the implications of implantation techniques have markedly reduced the risk of stent failure, both in the form of stent thrombosis (ST) and in-stent restenosis (ISR). However, given the number of percutaneous coronary interventions (PCI) performed worldwide every year, ST and ISR, albeit occurring at a fairly low rate, represent a public health problem even with contemporary DES platforms. The understanding of mechanisms and risk factors for these two PCI complications has been of fundamental importance for the parallel evolution of stent technologies. Risk factors associated with ST and ISR are usually divided into patient-, lesion-, device- and procedure-related. A number of studies have shown how certain risk factors are related to early (1 month) versus late/very late ST (between 1 month and 1 year and >1 year, respectively). However, more research is required to conclusively show the role of time-dependence of risk factors also in the incidence of ISR (early [1 year] or late [>1 year]). A thorough risk assessment is required due to the complex etiology of ST and ISR. The most effective strategy to treat ST and ISR is still to prevent them; hence, it is crucial to identify patient-, lesion-, device- and procedure-related predictors. Full article

Hypopharyngeal cancer is usually diagnosed at an advanced stage and is associated with a high risk of recurrence and poor survival rates. Although they differ greatly in terms of prognosis, hypopharyngeal cancers are usually treated together with laryngeal cancers in clinical trials. Therefore, there are very few studies that focus specifically on patients with hypopharyngeal carcinoma. As a result, the therapeutic management of these patients is highly debated, and their clinical outcomes are poorly reported. The aim of this review is therefore to discuss the current therapeutic options in patients with hypopharyngeal carcinoma and their oncologic and functional outcomes. Patients with early-stage tumors can be treated either by conservative surgery (including transoral robot-assisted surgery) or by RT alone. However, most patients are diagnosed with locally advanced tumors that cannot be treated surgically without total laryngectomy. In this situation, the critical issue is to select the patients eligible for a larynx preservation therapeutic program. However, radical surgery with total laryngectomy still plays an important role in the management of patients with hypopharyngeal carcinoma, either as the primary treatment modality (T4 resectable primary tumor, contraindication to larynx preservation therapies) or, more commonly, as salvage treatment. Full article

Background: Data on the outcomes of restrictive cardiomyopathy (RCM) are limited, when the condition is complicated with arrhythmia. This study was designed to investigate the prevalence of atrial fibrillation (AF), ventricular tachycardia (VT) and bradycardia (BC) and their impact on adverse outcomes (intra-cardiac thrombus, stroke and systematic embolism [SSE], heart failure and death) of RCM. Methods and Results: The retrospective cohort study used data collected from the Beijing Municipal Health Commission Information Center (BMHCIC) database from 1 January 2010 to 31 December 2020. There were 745 (64.9%) patients with AF, 117 (10.2%) patients with VT and 311 (27.1%) patients with bradycardia. The presence of AF was associated with an increased risk of SSE (adjusted HR:1.37, 95%CI:1.02–1.83, p = 0.04) and heart failure (aHR:1.36, 95%CI:1.17–1.58, p < 0.001). VT was associated with an increased risk of intracardiac thrombus (aHR:2.34, 95%CI:1.36–4.01, p = 0.002) and death (aHR:2.07, 95%CI:1.19–3.59, p = 0.01). Bradycardia did not increase the adverse outcomes in RCM. The results remained consistent and steady when AF, VT and bradycardia were adjusted as competing factors. Conclusions: Cardiac arrhythmia are highly prevalent and associated with adverse outcomes in patients with RCM. AF and VT are more likely to be associated with intracardiac thrombosis, and the presence of AF increased the risk of SSE and HF. The presence of VT increased the risk of death. Full article

Introduction. As has been established, the left ventricle (LV) and the left atrium (LA) form an organic unit of the left heart; however, little is known about the dependence of LV rotational parameters on LA volumes, even in healthy circumstances. Therefore, the present study aimed to assess the associations between basal and apical LV rotations and LA volumes and volume-based functional properties throughout the cardiac cycle in healthy adults by three-dimensional speckle-tracking echocardiography. Methods. The present study comprised 167 healthy adults (age: 33.4 ± 12.6 years, 77 males) with normally directed LV rotational mechanics. All subjects underwent complete two-dimensional Doppler echocardiography with three-dimensional speckle-tracking echocardiography (3DSTE)-derived data acquisition. The 3DSTE-derived LA volumes and LV rotational parameters were determined at a later date. Results. An increasing end-systolic maximum LA volume (Vmax) was associated with increasing pre-atrial-contraction early (VpreA) and minimum end-diastolic (Vmin) LA volumes, and all stroke volumes were increased as well. Systolic basal left ventricular rotation (LVrot) was highest in the case of the highest systolic Vmax and early-diastolic VpreA. Apical LVrot did not show obvious associations with any increasing LA volumes. The highest systolic basal LVrot was associated with significantly increased diastolic VpreA and Vmin. Reduced diastolic LA volumes (VpreA, Vmin) were seen in the case of increased apical LVrot. An increasing basal LVrot was associated with the tendentious lowering of the apical LVrot and the significant elevation of LV twist. Similarly, an increasing apical LVrot was associated with the tendentious lowering of basal LVrot and the significant elevation of LV twist. Conclusions. Strong associations and adaptations between 3DSTE-derived LA volumes throughout the cardiac cycle and LV rotational mechanics were evidenced, even in healthy circumstances. Full article

In order to explore the factors affecting patients’ level of activities of daily living (ADL) on discharge after undergoing bipolar hemiarthroplasty or total hip arthroplasty for displaced femoral neck fractures at an acute care hospital, patient data were analyzed with the following statistical tools: multiple regression analysis (MRA), structural equation modeling (SEM), and simultaneous analysis of several groups (SASG). The Barthel Index (BI) on discharge was set as the objective variable, while age, sex, degree of dementia, BI on admission, number of days from admission to surgery, surgical option, and number of rehabilitation units per day were set as explanatory variables. Factors such as age, sex, degree of dementia, BI on admission, and number of rehabilitation units per day were significant in MRA. While not significant in MRA, the number of days from admission to surgery was significant in SEM. According to the SASG, the number of rehabilitation units per day was significant for patients without dementia but not for patients with dementia. Analysis of real-world data suggests that early surgery and rehabilitation affect ADL on discharge to a greater degree than the surgical method. For patients without dementia, longer daily rehabilitation was significantly associated with better ADL on discharge. Full article

Heart transplantation remains the gold standard for the treatment of advanced heart failure (HF). Identification of the etiology of HF is mandatory, as the specific pathology can determine subsequent treatment. Early identification of familial hypercholesterolemia (FH), the most common genetic disorder associated with premature cardiovascular disease, has a potential important impact on clinical management and public health. We evaluated the genetic information in the genes associated with FH in a cohort of 140 heart-transplanted patients. All patients underwent NGS genetic testing including LDLR, APOB, and PCSK9. We identified four carriers of rare pathogenic variants in LDLR and APOB. Although all four identified carriers had dyslipidemia, only the one carrying the pathogenic variant LDLR c.676T>C was transplanted due to CAD. Another patient with heart valvular disease was carrier of the controversial LDLR c.2096C>T. Two additional patients with non-ischemic dilated cardiomyopathy were carriers of variants in APOB (c.4672A>G and c.5600G>A). In our cohort, we identified the genetic cause of FH in patients that otherwise would not have been diagnosed. Opportunistic genetic testing for FH provides important information to perform personalized medicine and risk stratification not only for patients but also for relatives at concealed high cardiovascular risk. Including the LDLR gene in standard NGS cardiovascular diagnostics panels should be considered. Full article

Bileaflet Mitral Valve Prolapse (bMVP) has been linked to major arrhythmic events and sudden cardiac death (SCD). Consistent predictors in this field are still lacking. Echocardiography is the best tool for the analysis of the prolapse and its impact on the ventricular mechanics. The aim of this study was to find new echocardiographic predictors of malignant events within an arrhythmic MVP population. We evaluated 22 patients with bMVP with a transthoracic echocardiogram focused on mitral valve anatomy and ventricular contraction. Six of them had major arrhythmic events who required ICD implantation (ICD-MVP group), while sixteen of them presented with a high arrhythmic burden without major events (A-MVP group). The best predictors of malignant events were the AML length and MD of basal and mid-ventricular segments, while other significant predictors were the larger mitral valve annulus (MVA) indexed area, lower MVA anteroposterior diameter/AML length ratio, higher inferolateral basal S3 velocity and a greater mechanical dispersion (MD) of the basal and mid-ventricular segments. Full article

There is a trend towards the formalization of the rehabilitation process for older rehabilitants in a Challenging Rehabilitation Environment (CRE). This concept involves the comprehensive organization of care, support, and environment on rehabilitation wards. So far, literature on the principles of the CRE is scarce. This study aims to explore the perspectives regarding the CRE of healthcare professionals through a qualitative study. Therefore, between 2018 and 2020, six international and 69 Dutch professionals were interviewed in focus groups, and 180 professionals attended workshops on two Dutch congresses. Data were thematically analyzed using ATLAS.ti. Seven themes emerged regarding the rehabilitation processes: (1) rehabilitant (attention for cognitive functioning and resilience); (2) goals (setting personal goals); (3) exercise (increasing exercise intensity); (4) daily schedule (following the daily rhythm); (5) involving the client system (involving informal caregivers); (6) nutrition (influences rehabilitation capability); and (7) technology (makes rehabilitation more safe and challenging). Regarding organizational aspects, four main themes were identified: (1) environmental aspects (encourages exercises); (2) staff aspects (interdisciplinary team); (3) organizational aspects (implementing CRE requires a shared vision); and (4) factors outside the ward (a well-prepared discharge process). To offer effective rehabilitation, all elements of the CRE should be applied. To improve the CRE, specific interventions need to be developed and implemented. Consequently, the effectiveness and efficiency of the CRE need to be measured with validated tools. Full article

Current descriptions of the history of subtotal cholecystectomy require more details and accuracy. This study presented a narrative review of the articles on partial resections of the gallbladder published between 1898 and 2022. The Scale for the Assessment of Narrative Review Articles items guided the style and content of this paper. The systematic literature search yielded 165 publications. Of them, 27 were published between 1898 and 1984. The evolution of the partial resections of the gallbladder began in the last decade of the 19th century when Kehr and Mayo performed them. The technique of partial resection of the gallbladder leaving the hepatic wall in situ was well known in the 3rd and 4th decades of the 20th century. In 1931, Estes emphasised the term ‘partial cholecystectomy’. In 1947, Morse and Barb introduced the term ‘subtotal cholecystectomy’. Madding and Farrow popularised it in 1955–1959. Bornman and Terblanche revitalised it in 1985. This term became dominant in 2014. From a subtotal cholecystectomy technical execution perspective, it is either a single-stage (when it includes only the resectional component) or two-stage (when it also entails closure of the remnant of the gallbladder or cystic duct) operation. Recent papers on classifications of partial resections of the gallbladder indicate the extent of gallbladder resection. Subtotal cholecystectomy is an umbrella term for incomplete cholecystectomies. ‘Subtotal open-tract cholecystectomy’ and ‘subtotal closed-tract cholecystectomy’ are terms that characterise the type of completion of subtotal cholecystectomy. Full article

Neuroendocrine tumors are a rare type of cancer found in hormone-producing cells throughout the body. Research on disease-specific patient education assessments in this population is lacking. We previously demonstrated the feasibility and validity of NET VITALS, a patient-centered self-assessment designed to improve patients’ knowledge of their neuroendocrine tumor diagnosis/treatment and facilitate communication with their physician. In this report, we provide a brief overview of patient assessments that have been used for patients with neuroendocrine tumors. We summarize NET VITALS and present a proposed infrastructure for its implementation into standard clinical care in both academic and community practice settings at City of Hope. Incorporating NET VITALS into standard of care treatment for patients with neuroendocrine tumors may improve patients’ overall clinical care experience. Full article

Retinopathy of prematurity (ROP) is a leading cause of childhood blindness. Not only do the epidemiologic determinants and distributions of patients with ROP vary worldwide, but clinical differences have also been described. The Third Edition of the International Classification of ROP (ICROP3) acknowledges that aggressive ROP (AROP) can occur in larger preterm infants and involve areas of the more anterior retina, particularly in low-resource settings with unmonitored oxygen supplementation. As sub-specialty training programs are underway to address an epidemic of ROP in sub-Saharan Africa, recognizing characteristic retinal pathology in preterm infants exposed to unmonitored supplemental oxygen is important to proper diagnosis and treatment. This paper describes specific features associated with various ROP presentations: oxygen-induced retinopathy in animal models, traditional ROP seen in high-income countries with modern oxygen management, and ROP related to excessive oxygen supplementation in low- and middle-income countries: oxygen-associated ROP (OA-ROP). Full article

Background: Combining traditional clinical parameters with neuroendocrine markers to construct a nomogram model to predict the postoperative recurrence of neuroendocrine carcinoma of cervix (NECC). Methods: A total of 257 patients were included in this study. Univariate and multivariate Cox regression analyses were used to establish a nomogram model in the training cohorts, which was further validated in the validation cohorts. The calibration curve was used to conduct the internal and external verification of the model. Results: Overall, 41 relapse cases were observed in the training (23 cases) and validation (18 cases) cohorts. The univariate analysis preliminarily showed that FIGO stage, stromal invasion, nerve invasion, lymph vascular space invasion, lymph node involvement, cervical–uterine junction invasion and CgA were correlated with NECC recurrence. The multivariate analysis further confirmed that FIGO stage (p = 0.023), stromal invasion (p = 0.002), lymph vascular space invasion (p = 0.039) and lymph node involvement (p = 0.00) were independent risk factors for NECC recurrence, which were ultimately included in the nomogram model. In addition, superior consistency indices were demonstrated in the training (0.863, 95% CI 0.784–0.942) and validation (0.884, 95% CI 0.758–1.010) cohorts. Conclusions: The established nomogram model combining traditional clinical parameters with neuroendocrine markers can reliably and accurately predict the recurrence risks in NECC patients. Full article

Background: This aim of this study was to develop an objective tool for rating submental fat applied to Koreans. Methods: The study was conducted between April 2019 and October 2019. A total of 92 subjects were enrolled in the study. Clinical photos of the subjects were categorized using validated CR-SMFRS by three plastic surgeons and one dermatologist. The categorized photos were then shown to six different plastic surgeons for evaluation. Results: The Cohen’s kappa value for the six raters were 0.830, 0.742, 0.703, 0.907, 0.862, and 0.793 with statistical significance (p < 0.001). ICC value was between 0.860 and 0.966 (p < 0.001). Since the Cohen’s value and ICC were above 0.6 for all raters, the ratings performed by all six raters were used in the analysis. The ICC values between raters were between 0.899 and 0.902. Conclusions: We came up with a set of reference photos that can be used for submental fat rating scale applicable to Korean subjects. Level of Evidence: II. Full article