J. Clin. Med., Volume 10, Issue 9 (May-1 2021) – 244 articles

Patients with irritable bowel syndrome (IBS) are at increased risk of osteoporosis and osteoporotic fracture. This study investigated whether IBS medication attenuated the rate of osteoporosis and osteoporotic fracture risk. We conducted a retrospective large-scale multicenter study across eight hospital databases encoded in the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM). The primary outcome was the incidence of osteoporosis, whereas secondary outcomes were osteoporotic fractures. After 1:4 matching, 24,723 IBS patients, 78,318 non-IBS patients, 427,640 non-IBS patients with IBS medication, and 827,954 non-IBS patients without IBS medication were selected. The risk of osteoporosis was significantly increased in the IBS group compared to the non-IBS group (hazard ratio (HR) 1.33; confidence interval (CI) 1.17~1.51). Even in patients who were not diagnosed with IBS, the risk of osteoporosis was significantly increased in those with IBS medication compared to those without (HR 1.77, CI 1.62~1.93). The risk of osteoporotic fracture was significantly increased in the IBS medication group (HR 1.69, CI 1.55~1.84). Patients exposed to IBS treatment even without IBS diagnosis were at increased risk of osteoporosis and osteoporotic fracture. Early diagnosis and treatment of osteoporosis should be considered in patients who have received medication for IBS symptoms. Full article

There has been an increasing worldwide incidence of invasive group A streptococcal (GAS) disease in pregnancy and in the puerperal period over the past 30 years. Postpartum Group A streptococci infection, and in particular streptococcal toxic shock syndrome (TSS) and necrotizing fasciitis, can be life threatening and difficult to treat. Despite antibiotics and supportive therapy, and in some cases advanced extensive surgery, mortality associated with invasive group A streptococcal postpartum endometritis, necrotizing fasciitis, and toxic shock syndrome remains high, up to 40% of postpartum septic deaths. It now accounts for more than 75,000 deaths worldwide every year. Postpartum women have a 20-fold increased incidence of GAS disease compared to non-pregnant women. Despite the high incidence, many invasive GAS infections are not diagnosed in a timely manner, resulting in potentially preventable maternal and neonatal deaths. In this paper the specific characteristics of GAS infection in the field of Ob/Gyn are brought to our attention, resulting in guidelines to improve our awareness, early recognition and timely treatment of the disease. New European prevalence data of vaginal GAS colonization are presented, alongside two original case histories. Additionally, aerobic vaginitis is proposed as a supplementary risk factor for invasive GAS diseases. Full article

Background: Patients with kidney failure are at an increased risk of progression to a severe form of coronavirus disease 2019 (COVID-19) with high mortality. The current analysis was aimed to assess the impact of renal failure on the severity of COVID-19 and identify the risk factors of the fatal outcome in this population. Methods: The analysis included patients from the SARSTer database, a national real-world study evaluating treatment for COVID-19 in 30 Polish centers. Data were completed retrospectively and submitted online. Results: A total of 2322 patients were included in the analysis. Kidney failure was diagnosed in 455 individuals (19.65%), of whom 373 presented moderate stage and 82 patients, including 14 dialysis individuals, presented severe renal failure. Patients with kidney failure were significantly older and demonstrated a more severe course of COVID-19. The age, baseline SpO₂, the ordinal scale of 4 and 5, neutrophil and platelet count, estimated glomerular filtration rate, and C-reactive protein concentration as well as malignancy and arterial hypertension were the independent predictors of 28-day mortality in logistic regression analysis. Conclusions: Underlying kidney disease in patients with COVID-19 is among the leading factors associated with a higher risk of severe clinical presentation and increased mortality rate. Full article

This systematic review aims to identify what rehabilitation care networks, within primary care or between primary and other health care settings, have been described for patients with chronic musculoskeletal pain, and what their impact is on the Quadruple Aim outcomes (health; health care costs; quality of care experienced by patients; work satisfaction for health care professionals). Studies published between 1 January 1994 and 11 April 2019 were identified in PubMed, CINAHL, Web of Science, and PsycInfo. Forty-nine articles represented 34 interventions: 21 within primary care; 6 between primary and secondary/tertiary care; 1 in primary care and between primary and secondary/tertiary care; 2 between primary and social care; 2 between primary, secondary/tertiary, and social care; and 2 between primary and community care. Results on impact were presented in 19 randomized trials, 12 non-randomized studies, and seven qualitative studies. In conclusion, there is a wide variety of content, collaboration, and evaluation methods of interventions. It seems that patient-centered interdisciplinary interventions are more effective than usual care. Further initiatives should be performed for interdisciplinary interventions within and across health care settings and evaluated with mixed methods on all Quadruple Aim outcomes. Full article

Non-alcoholic fatty liver disease is a highly prevalent disease worldwide with a renowned relation to cardiovascular disease and chronic kidney disease. These diseases share a common pathophysiology including insulin resistance, oxidative stress, chronic inflammation, dysbiosis and genetic susceptibilities. Non-alcoholic fatty liver disease is especially prevalent and more severe in type 2 diabetes. Patients with non-alcoholic fatty liver disease should have liver fibrosis assessment in order to identify those at the highest risk of adverse outcomes so that appropriate management strategies can be implemented. Early diagnosis and treatment of non-alcoholic fatty liver disease could ameliorate the burden of cardiovascular disease and chronic kidney disease. Full article

Background: Sleep disordered breathing (SDB) is a frequent comorbidity in cardiac disease patients. Nevertheless, the prevalence and relationship between SDB and severe primary mitral regurgitation (PMR) has not been well investigated to date. Methods: A cohort of 121 patients with significant PMR undergoing mitral valve surgery were prospectively enrolled and received a cardiorespiratory single night polygraphy screening using ApneaLink before surgery. Eighty-two of them underwent a follow-up examination including a follow-up single-night sleep study 3 months after surgery. Results: The mean age of patients was 65.3 ± 12.0 years. Sixty patients (49.6%) were female. The mean EuroSCORE II was 2.5 ± 2.4%. Initially, 91 (75.2%) patients presented with SDB, among whom 50.4% (46 patients, 38.0% of total cohort) were classified as moderate to severe. These patients tended to require significantly longer postoperative intensive care and mechanical ventilation. Among the 82 patients who completed follow-up exams, mitral valve surgery led to a significant reduction in relevant SDB (20.7%). The apnea-hypopnea index (from 11/h [4;18] to 4/h [3;14] (p = 0.04)), the oxygenation-desaturation index (from 8/h [3;18] to 5/h [3;12] (p = 0.008)) as well as the saturation time below 90% (from 32 min [13;86] to 18 min [5;36] (p = 0.005)), were all shown to be improved significantly. Conclusion: The prevalence of SDB is very high in patients with severe primary mitral regurgitation and may contribute to postoperative complications and prolonged intensive care. A significantly reduced but still high prevalence of SDB was observed 3 months after mitral valve surgery, highlighting the bidirectional relationship between SDB and heart failure. Full article

Background: We aimed to investigate molecular factors potentially related to the progression of gastric adenoma (GA) to gastric cancer (GC) and compare the mutation characteristics between GC and GA. Methods: We conducted custom gene panel sequencing for 135 GC-related genes and estimated the difference in somatic mutation profiles between 20 GC and 20 GA cases. Results: A total of 31 somatic mutations, including 22 missense, 3 nonsense, and 6 frameshift mutations, were detected in 17 samples. We estimated an average of 1.8 mutations per sample (range, 1 to 3 mutations), with 12 in GC and 5 in GA. GC tended to have one or more mutated genes (p = 0.0217), as well as higher allele frequencies of mutated genes (p = 0.0003), compared to GA. Likewise, known driver mutations associated with GC tumorigenesis (TP53, ERBB2, PIK3CA, and RNF43) were identified in half of the GC cases (50%, 10/20; p = 0.0002). Only the mutant burden, regardless of gene type, was retained, with an odds ratio of 1.8392 (95% confidence interval (CI), 1.0071 to 3.3588; p = 0.0474). Conclusion: Our study demonstrates that the accumulation of mutant burden contributes to tumorigenesis progression from GA to GC in Korean patients, regardless of the kind of genes. These findings may elucidate the molecular pathogenesis of gastric carcinogenesis and malignant progression. Full article

Many anterior C2 (2nd cervical vertebra) tear drop (TD) fractures can be successfully managed with conservative treatment. However, due to the occurrence of nonunion, large-sized or complex anterior C2 TD fractures undergo surgical treatment. To date, no surgical treatment guidelines are available about anterior C2 TD fractures. Therefore, we performed this study to investigate the factors that may affect nonunion for anterior C2 TD fractures and to suggest surgical treatment guidelines. Thirty-three patients with anterior C2 TD fractures, who underwent conservative treatment and had a minimum 1-year follow-up, were divided into union (N = 26) and nonunion (N = 7) groups. Their radiological and clinical data were analyzed retrospectively and compared between the two groups. The avulsion fracture ratio (29.5% vs. 43.3%, p < 0.05) and fracture displacement (3.6 mm vs. 5.1 mm, p < 0.05) were higher in the nonunion group compared to the union group. Incidence of associated C2 injury was higher in the nonunion group compared to the union group (15.4% vs. 57.1%, p < 0.05). Union status was negatively correlated with associated C2 injury (correlation coefficient, CC = −0.398, p < 0.05). Our results suggest that surgical treatment could be considered for anterior C2 TD fractures with an avulsion fracture ratio > 43%, fracture displacement > 5 mm, or associated C2 injury. Full article

Canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin belong to a class of antidiabetic treatments referred to as sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors, or SGLT2is). SGLT2is are currently indicated in North America and in Europe in type 2 diabetes mellitus, especially in patients with cardiovascular (CV) disease, high CV risk, heart failure, or renal disease. In Europe, dapagliflozin is also approved as an adjunct to insulin in patients with type 1 diabetes mellitus. New data provide evidence for benefits in heart failure with reduced ejection fraction and chronic kidney disease, including in patients without diabetes. The use of SGLT2is is expected to increase, suggesting that a growing number of patients will present to the emergency departments with these drugs. Most common adverse events are easily treatable, including mild genitourinary infections and conditions related to volume depletion. However, attention must be paid to some potentially serious adverse events, such as hypoglycemia (when combined with insulin or insulin secretagogues), lower limb ischemia, and diabetic ketoacidosis. We provide an up-to-date practical guide highlighting important elements on the adverse effects of SGLT2is and their handling in some frequently encountered clinical situations such as acute heart failure and decompensated diabetes. Full article

Achievement of complete resections is of utmost importance in brain tumor surgery, due to the established correlation among extent of resection and postoperative survival. Various tools have recently been included in current clinical practice aiming to more complete resections, such as neuronavigation and fluorescent-aided techniques, histopathological analysis still remains the gold-standard for diagnosis, with frozen section as the most used, rapid and precise intraoperative histopathological method that permits an intraoperative differential diagnosis. Unfortunately, due to the various limitations linked to this technique, it is still unsatisfactorily for obtaining real-time intraoperative diagnosis. Confocal laser technology has been recently suggested as a promising method to obtain near real-time intraoperative histological data in neurosurgery, due to its established use in other non-neurosurgical fields. Still far to be widely implemented in current neurosurgical clinical practice, this technology was initially studied in preclinical experiences confirming its utility in identifying brain tumors, microvasculature and tumor margins. Hence, ex vivo and in vivo clinical studies evaluated the possibility with this technology of identifying and classifying brain neoplasms, discerning between normal and pathologic tissue, showing very promising results. This systematic review has the main objective of presenting a state-of-the-art summary on actual clinical applications of confocal laser imaging in neurosurgical practice. Full article

Background: Anterior cervical discectomy and fusion surgery is a common procedure for degenerative cervical spine. This describes allospacer and implant-related outcomes, comparing medium plate–low screw angle and short plate–high screw angle techniques. Methods: From January 2016 to June 2019, 79 patients who underwent ACDF were prospectively enrolled. Patients were divided, depending on the plate–screw system used: medium plate–low screw angle (12.3 ± 2.5 to 13.2 ± 3.2 degrees), and short plate–high screw angle (22.8 ± 5.3 to 23.3 ± 4.7 degrees). Subsidence, ALOD, and sagittal cervical balance were analyzed using lateral cervical X-rays. NDI and VAS scores were also evaluated. Results: Age for medium plate–low-angled screw group is 58.0 ± 11.3 years, and 55.3 ± 12.0 in the short plate–high-angled screw group (p-value = 0.313). Groups were comparable in mean NDI (p-value = 0.347), VAS (p-value = 0.156), C2–C7 SVA, (p-value = 0.981), and lordosis angle (p-value = 0.836) at 1-year post-surgery. Subsidence was higher in the medium plate–low-angled screw than in the short plate–high-angled screw (25% and 8.5%, respectively, p-value = 0.045). ALOD is also more common in the medium plate group (p-value = 0.045). Conclusion: Use of a short plate and insertion of high-angled screws (more than 20 degrees) has less chance of subsidence and occurrence of ALOD than the traditional technique of using medium plate and low angle. Full article

The objective of this study was to determine the value of uterocervical angle (UCA) in predicting successful induction of labor (IOL) in singleton pregnant women compared to the Bishop score and cervical length (CL). A total of 205 normal term, singleton labor-induction cases were analyzed. Successful IOL was defined as the onset of active labor of induction. A comparative analysis was performed to evaluate the effectiveness of UCA, Bishop score, and CL in predicting IOL. Compared to the non-successful IOL group, the women in the successful IOL group had significantly wider UCA (p = 0.012) and higher Bishop score (p = 0.001); however, the CL was not significantly different (p = 0.130). UCA alone did not perform better than the Bishop score when predicting successful IOL. However, UCA combined with the Bishop score showed higher performance in predicting IOL (combined UCA > 108.4° and favorable Bishop score as sensitivity of 44.6%, specificity of 96.0%, PPV of 96.2%, and NPV of 43.6; combined UCA > 108.4° or favorable Bishop score as sensitivity of 85.7%, specificity of 50.0%, PPV of 78.7%, and NPV of 61.9). In conclusion, UCA combined with Bishop score may be an effective sonographic method for predicting successful IOL. Full article

Background: Non-adherence with immunosuppressant medication (MNA) fosters development of de novo donor-specific antibodies (dnDSA), rejection, and graft failure (GF) in kidney transplant recipients (KTRs). However, there is no simple tool to assess MNA, prospectively. The goal was to monitor MNA and analyze its predictive value for dnDSA generation, acute rejection and GF. Methods: We enrolled 301 KTRs in a multicentric French study. MNA was assessed prospectively at 3, 6, 12, and 24 months (M) post-KT, using the Morisky scale. We investigated the association between MNA and occurrence of dnDSA at year 2 post transplantation, using logistic regression models and the association between MNA and rejection or graft failure, using Cox multivariable models. Results: The initial percentage of MNA patients was 17.7%, increasing to 34.6% at 24 months. Nineteen patients (8.4%) developed dnDSA 2 to 3 years after KT. After adjustment for recipient age, HLA sensitization, HLA mismatches, and maintenance treatment, MNA was associated neither with dnDSA occurrence, nor acute rejection. Only cyclosporine use and calcineurin inhibitor (CNI) withdrawal were strongly associated with dnDSA and rejection. With a median follow-up of 8.9 years, GF occurred in 87 patients (29.0%). After adjustment for recipient and donor age, CNI trough level, dnDSA, and rejection, MNA was not associated with GF. The only parameters associated with GF were dnDSA occurrence, and acute rejection. Conclusions: Prospective serial monitoring of MNA using the Morisky scale does not predict dnDSA occurrence, rejection or GF in KTRs. In contrast, cyclosporine and CNI withdrawal induce dnDSA and rejection, which lead to GF. Full article

Glioblastoma multiforme (GBM) carries a poor prognosis and usually presents with heterogenous regions of a necrotic core, solid part, peritumoral tissue, and peritumoral edema. Accurate demarcation on magnetic resonance imaging (MRI) between the active tumor region and perifocal edematous extension is essential for planning stereotactic biopsy, GBM resection, and radiotherapy. We established a set of radiomics features to efficiently classify patients with GBM and retrieved cerebral multiparametric MRI, including contrast-enhanced T1-weighted (T1-CE), T2-weighted, T2-weighted fluid-attenuated inversion recovery, and apparent diffusion coefficient images from local patients with GBM. A total of 1316 features on the raw MR images were selected for each annotated area. A leave-one-out cross-validation was performed on the whole dataset, the different machine learning and deep learning techniques tested; random forest achieved the best performance (average accuracy: 93.6% necrosis, 90.4% solid part, 95.8% peritumoral tissue, and 90.4% peritumoral edema). The features from the enhancing tumor and the tumor shape elongation of peritumoral edema region for high-risk groups from T1-CE. The multiparametric MRI-based radiomics model showed the efficient classification of tumor subregions of GBM and suggests that prognostic radiomic features from a routine MRI exam may also be significantly associated with key biological processes that affect the response to chemotherapy in GBM. Full article

Computed tomography-guided needle biopsy (CT-GNB) has a high diagnostic yield for lung cancer but higher complication rates compared to those of other biopsy modalities. We sought to clarify in which thoracic lesions we could achieve a quick pathological diagnosis using CT-GNB, considering the risks and benefits. We retrospectively enrolled 110 patients who underwent CT-GNB and 547 patients who underwent transbronchial biopsy (TBB) for parenchymal lung lesions in clinical practice. The diagnostic rates of CT-GNB and TBB were 87.3% and 75.3%. After failed diagnosis with other biopsy modalities, 92.3% of patients were finally diagnosed using CT-GNB and 65.8% using TBB. In cases with a negative bronchial sign, there was a statistically higher diagnostic rate with CT-GNB than with TBB (p < 0.001: 89.4% vs. 0%). Complication rates were higher with CT-GNB (50.9%) than with TBB (16.3%). However, there were lower rates of complications in cases with inhomogeneous tumors, subpleural lesions, and when more than 15 mm of the punctured needle length was within the target. We conclude that CT-GNB is an effective biopsy modality with a high diagnostic rate that is especially recommended when the bronchus sign is negative. It can be safely performed if risk factors for complications are taken into account. Full article

(1) Objective: To analyze the exercise programs used to prevent of acute hamstring injuries in eleven-a-side football players, and their effectiveness. (2) Methods: A systematic review (PRISMA) was conducted (2008–2020), including RCTs, that exclusively used physical exercises as a prevention method. (3) Results: Ten studies were selected considering 14 interventions, including nine different programs: FIFA11+ (11+), Harmoknee, eccentric Nordic Hamstring Exercise (NHE) exclusively, with eccentric exercises, with stretching or with proprioceptive, New Warm-up Program (NWP), Bounding Exercise Program (BEP), the only one with no positive results, and proprioceptive exercises. Incidence of injuries and strength were the most considered variables, both with favorable evidences. Programs including NHE, which assessed injury incidence, were always effective. The 11+ program was effective in injury incidence and strength; NWP was effective in balance, stability, and strength. (4) Conclusions: The exercise programs discussed were effective to prevent acute hamstring injuries in football players except BEP and partially Harmoknee. Exercises mostly used to reduce the risk of hamstring injuries are those of eccentric force due to its functionality, especially NHE. Only concentric contractions and isometric contractions obtained significant favorable results. The most complete and promising programs were 11+ (in injury incidence and strength) and NWP (strength, balance, and stability). NWP was the best in strength. Full article

Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in children, yet little is known about its etiology. Studies that examine either environmental exposures or germline genetic predisposition in RMS have begun to identify factors that contribute to this malignancy. Here, we summarize epidemiological reports of RMS incidence in terms of several factors, including age at diagnosis, biological sex, and geographic location. We then describe findings from association studies, which explore the role of parental exposures, birth and perinatal characteristics, and childhood exposures in RMS. Further, we discuss RMS predisposition syndromes and large-scale sequencing studies that have further identified RMS-associated genes. Finally, we propose future directions of study, which aim to advance our understanding of the origin of RMS and can provide knowledge for novel RMS therapies. Full article

Patients with chronic constipation who do not respond to initial treatments often need further evaluation for dyssynergic defecation (DD) and slow transit constipation (STC). The aims of this study are to characterize the prevalence of DD and STC in patients referred to a motility center with chronic constipation and correlate diagnoses of DD and STC to patient demographics, medical history, and symptoms. High-resolution ARM (HR-ARM), balloon expulsion testing (BET) and whole gut transit scintigraphy (WGTS) of consecutive patients with chronic constipation were reviewed. Patients completed questionnaires describing their medical history and symptoms at the time of testing. A total of 230 patients completed HR-ARM, BET, and WGTS. Fifty (22%) patients had DD, and 127 (55%) patients had STC. Thirty patients (13%) had both DD and STC. There were no symptoms that were suggestive of STC vs. DD; however, patients with STC and DD reported more severe constipation than patients with normal transit and anorectal function. Patients with chronic constipation often need evaluation for both DD and STC to better understand their pathophysiology of symptoms and help direct treatment. Full article

While normal-pressure hydrocephalus (NPH) is most commonly diagnosed in older adulthood, a significant body of literature has accumulated over half a century documenting the clinical phenomenon of an NPH-like syndrome in pediatric patients. As in adult NPH, it is likely that pediatric NPH occurs due to a heterogeneous array of developmental, structural, and neurodegenerative pathologies, ultimately resulting in aberrant cerebrospinal fluid (CSF) flow and distribution within and around the brain. In this review, we aimed to systematically survey the existing clinical evidence supporting the existence of a pediatric form of NPH, dating back to the original recognition of NPH as a clinically significant subtype of communicating hydrocephalus. Leveraging emergent trends from the old and more recent published literature, we then present a modern characterization of pediatric NPH as a disorder firmly within the same disease spectrum as adult NPH, likely with overlapping etiology and pathophysiological mechanisms. Exemplary cases consistent with the diagnosis of pediatric NPH selected from the senior author’s neurosurgical practice are then presented alongside the systematic review to aid in discussion of the typical clinical and radiographic manifestations of pediatric NPH. Common co-morbidities and modern surgical treatment options are also described. Full article

Several studies reported a high prevalence of cardiovascular risk factors among police officers and office workers, and adequate cardiorespiratory fitness was reported to have protective effects in reducing cardiovascular risk. Therefore, the present study aimed to evaluate the effects of cardiorespiratory fitness on reducing cardiovascular risk factors in these occupational groups. This cross-sectional study enrolled 101 male participants (55 police officers and 46 office workers). Cardiorespiratory fitness was assessed via spiroergometry. Cardiovascular risk factors were also examined, and the 10-year cardiovascular risk and heart/vascular age were reported using the Framingham risk score. In both groups, higher cardiorespiratory fitness was associated with lower cardiovascular risk factors. Police officers and office workers with higher cardiorespiratory fitness demonstrated significantly lower values in BMI, waist circumference, body fat percentage, diastolic resting blood pressure, heart rate, triglycerides and total cholesterol values, and 10-year cardiovascular risk and heart/vascular age (all factors p < 0.0077, age adjusted). Police officers and office workers mostly presented low levels of cardiorespiratory fitness: 60% of police officers and 58% of office workers were considered “not fit and obese”. Despite different working conditions, both occupational groups had a high rate of low cardiorespiratory fitness levels and showed no differences in their cardiovascular risk profiles. In both groups, cardiorespiratory fitness reduced cardiovascular risk factors, but there was no difference in the influence of cardiorespiratory fitness on cardiovascular risk factors. Full article

The right ventricle (RV) is more sensitive to an increase in afterload than the left ventricle (LV), and RV afterload during exercise increases more easily than LV afterload. Pulmonary arterial hypertension (PAH)-specific therapy has improved pulmonary hemodynamics at rest; however, the pulmonary hemodynamic response to exercise is still abnormal in most patients with PAH. In these patients, RV afterload during exercise could be higher, resulting in a greater increase in RV wall stress. Recently, an increasing number of studies have indicated the short-term efficacy of exercise training. However, considering the potential risk of promoting myocardial maladaptive remodeling, even low-intensity repetitive exercise training could lead to long-term clinical deterioration. Further studies investigating the long-term effects on the RV and pulmonary vasculature are warranted. Although the indications for exercise training for patients with PAH have been expanding, exercise training may be associated with various risks. Training programs along with risk stratification based on the pulmonary hemodynamic response to exercise may enhance the safety of patients with PAH. Full article

Hereditary angioedema is a rare inherited disorder characterized by recurrent episodes of the accumulation of fluids outside of the blood vessels, causing rapid swelling of tissues in the hands, feet, limbs, face, intestinal tract, or airway. Mutations in SERPING1, the gene that encodes C1-INH (C1 esterase inhibitor), are responsible for the majority of cases of hereditary angioedema. C1 esterase inhibitor (C1-INH) is a major regulator of critical enzymes that are implicated in the cascades of bradykinin generation, which increases the vascular permeability and allows the flow of fluids into the extracellular space and results in angioedema. Moreover, a dominantly inherited disease has been described that has a similar clinical picture to C1-INH-HAE (Hereditary angioedema due to C1 inhibitor deficiency), but with normal C1-INH level and activity. This new type of HAE has no mutation in the SERPING1 gene and it is classified as nC1-INH-HAE (HAE with normal C1-INH). Currently mutations in six different genes have been identified as causing nC1-INH-HAE: factor XII (F12), plasminogen (PLG), angiopoietin 1 (ANGPT1), Kininogen 1 (KNG1), Myoferlin (MYOF), and heparan sulfate (HS)-glucosamine 3-O-sulfotransferase 6 (HS3ST6). In this review we aim to summarize the recent advances in genetic characterization of angioedema and possible future prospects in the identification of new genetic defects in HAE. We also provide an overview of diagnostic applications of genetic biomarkers using NGS technologies (Next Generation Sequencing). Full article

Introduction: Fungal infections remain a major challenge affecting outcomes after kidney (KT) and liver transplantation (LT). Methods: In this retrospective single center study, the incidence of Candida contamination in renal and hepatic graft preservation solution (PS) was evaluated. In addition, Candida associated infections in recipients and related complications were analyzed. Results: Overall, the PS of 1248 hepatic and 1273 renal grafts were evaluated. The incidence of fungal contamination in the PS of hepatic and renal grafts was 1.2% and 0.86%, respectively. Additionally, the hepatic PS of one patient who underwent a combined liver–kidney transplant had Candida contamination. Candida albicans was the most common organism (70.4%) and 65.4% of the patients received antifungal treatment. Candida-associated complications in the recipients was 19%. Complications in LT patients included Candida peritonitis and Candida sepsis. Two KT recipients with contaminated PS developed a mycotic aneurysm at the anastomotic site resulting in severe bleeding. The 1-year mortality in patients with PS contamination for LT and KT recipients was 33% and 18%, respectively. Although the incidence of fungal contamination of PS was low, contaminated PS was associated with a high mortality. Conclusion: The results of the study suggest that PS should be evaluated for fungal growth. Full article

Intercellular adhesion molecule-1 (ICAM-1) mediates extravasation of leukocytes, releasing proinflammatory cytokines or endogenous opioids in the inflamed tissue. Thus, ICAM-1 is a crucial component of peripheral antinociception. Previously, we demonstrated a significant correlation between the soluble form of ICAM (sICAM-1) in serum and pain intensity reported by chronic pain patients. The present study examines the role and kinetics of sICAM-1 in experimentally induced acute pain. Three groups of 10 subjects were exposed to 10 min of high (capsaicin-enhanced) or low-intensity heat pain or cold pain, respectively. Thermal stimuli were induced using a device for quantitative sensory testing. Topical capsaicin significantly increased heat pain intensity without the risk of thermal tissue damage. Pain intensity was recorded every minute during testing. sICAM-1 concentrations in serum were determined by ELISA before, immediately after, and 60 min after test termination. Among all experimental groups, sICAM-1 significantly decreased immediately after pain induction. After 60 min, sICAM-1 concentrations returned towards initial values. Interestingly, a linear correlation was found between the extent of sICAM-1 changes and the initial concentrations. Whereas high initial values led to a distinct decrease of sICAM-1, low concentrations tended to increase. There was no statistically significant correlation between levels or alterations of serum sICAM-1 and pain intensity reported by the test subjects. In contrast to our previous findings in chronic pain patients, the present results show that sICAM-1 values do not correlate with the intensity of acute experimental pain. However, we were able to detect short-term changes of sICAM-1 after induction of nociceptive thermal stimuli, suggesting that this marker is part of a demand-oriented homeostatically controlled system. Full article

Coronavirus disease 2019 (COVID-19), with a broad range of clinical and laboratory findings, is currently the most prevalent medical challenge worldwide. In this disease, hypercoagulability and hyperinflammation, two common features, are accompanied by a higher rate of morbidity and mortality. We assessed the association between baseline inflammatory cytokine levels and coagulopathy and disease outcome in COVID-19. One hundred and thirty-seven consecutive patients hospitalized with COVID-19 were selected for the study. Baseline interleukin-1 (IL-1), IL-6, and tumor necrosis factor alpha (TNF-α) level were measured at time of admission. At the same time, baseline coagulation parameters were also assessed during the patient’s hospitalization. Clinical findings, including development of thrombosis and clinical outcome, were recorded prospectively. Out of 136 patients, 87 (~64%) had increased cytokine levels (one or more cytokines) or abnormal coagulation parameters. Among them, 58 (~67%) had only increased inflammatory cytokines, 12 (~14%) had only coagulation abnormalities, and 17 (19.5%) had concomitant abnormalities in both systems. It seems that a high level of inflammatory cytokines at admission points to an increased risk of developing coagulopathy, thrombotic events, even death, over the course of COVID-19. Early measurement of these cytokines, and timely co-administration of anti-inflammatories with anticoagulants could decrease thrombotic events and related fatal consequences. Full article

Laryngeal neuroendocrine carcinomas (LNECs) are rare and highly heterogeneous malignancies presenting a wide range of pathological and clinical manifestations. Herein, we retrospectively characterize ten patients diagnosticated with LNEC, five of which were defined as well-moderately differentiated neuroendocrine carcinomas, and five that were defined as poorly differentiated neuroendocrine carcinomas, according to the latest WHO classification. Clinical features were analyzed and compared between the two subgroups together with a microRNA study which evidenced a peculiar signature likely related to poorly differentiated larynx neuroendocrine carcinomas. These findings may offer new useful insights for clinicians to improve diagnosis efficiency, therapy response, and patients’ outcome for this aggressive neoplasm. Full article

There is no information about whether fetal growth restriction (FGR) is an independent risk factor for low-grade fetal inflammatory response (FIR), and which is more valuable for the prediction of early-onset neonatal sepsis (EONS) between low-grade FIR or fetal inflammatory response syndrome (FIRS) in the context of human early preterm sterile intrauterine environment. We examined FIR (umbilical cord plasma (UCP) CRP concentration at birth) according to the presence or absence of FGR (birth weight < 5th percentile for gestational age (GA)) and EONS in 81 singleton preterm births (GA at delivery: 24.5~33.5 weeks) within 72 h after amniocentesis and with sterile intrauterine environment. A sterile intrauterine environment was defined by the presence of both a sterile amniotic fluid (AF) (AF with both negative culture and MMP-8 < 23 ng/mL) and inflammation-free placenta. Median UCP CRP (ng/mL) was higher in cases with FGR than in those without FGR (63.2 vs. 34.5; p = 0.018), and FGR was an independent risk factor for low-grade FIR (UCP CRP ≥ 52.8 ng/mL) (OR 3.003, 95% CI 1.024–8.812, p = 0.045) after correction for confounders. Notably, low-grade FIR (positive likelihood-ratio (LR) and 95% CI, 2.3969 (1.4141–4.0625); negative-LR and 95% CI, 0.4802 (0.2591–0.8902)), but not FIRS (positive-LR and 95% CI, 2.1071 (0.7526–5.8993); negative-LR and 95% CI, 0.8510 (0.6497–1.1145)), was useful for the identification of EONS. In conclusion, FGR is an independent risk factor for low-grade FIR, and low-grade FIR, but not FIRS, has a value for the identification of EONS in the context of the early preterm sterile intrauterine environment. Full article

Pneumonia is the leading cause of hospital admission and mortality in coronavirus disease 2019 (COVID-19). We aimed to identify the cytokines responsible for lung damage and mortality. We prospectively recruited 108 COVID-19 patients between March and April 2020 and divided them into four groups according to the severity of respiratory symptoms. Twenty-eight healthy volunteers were used for normalization of the results. Multiple cytokines showed statistically significant differences between mild and critical patients. High HGF levels were associated with the critical group (OR = 3.51; p < 0.001; 95%CI = 1.95–6.33). Moreover, high IL-1α (OR = 1.36; p = 0.01; 95%CI = 1.07–1.73) and low IL-27 (OR = 0.58; p < 0.005; 95%CI = 0.39–0.85) greatly increased the risk of ending up in the severe group. This model was especially sensitive in order to predict critical status (AUC = 0.794; specificity = 69.74%; sensitivity = 81.25%). Furthermore, high levels of HGF and IL-1α showed significant results in the survival analysis (p = 0.033 and p = 0.011, respectively). HGF, IL-1α, and IL 27 at hospital admission were strongly associated with severe/critical COVID-19 patients and therefore are excellent predictors of bad prognosis. HGF and IL-1α were also mortality biomarkers. Full article

The cardiothoracic ratio (CTR), expressing the relationship between the size of the heart and the transverse dimension of the chest measured on a chest PA radiograph, is a commonly used parameter in the assessment of cardiomegaly with a cut-off value of 0.5. A value of >0.5 should be interpreted as enlargement of the heart. The following review describes the current state of available knowledge in terms of contentious issues, limitations and useful aspects regarding the CTR. The review was carried out on the basis of an analysis of scientific articles available in the PubMed database, searched for using the following keywords: “CTR”, “cardiothoracic ratio”, “cardiopulmonary ratio”, “cardiopulmonary index”, and “heart-lung ratio”. According to the accumulated knowledge, the CTR can still be used as an important parameter that can be easily determined in establishing enlargement of the heart. However, an increased CTR does not directly relate to heart function. In the era following the development of diagnostic methods such as computed tomography, magnetic resonance imaging, and ultrasonography, CTR modifications based on these methods are used with varying clinical usefulness. It is important to consider the definition of the CTR and remember to base measurements on PA radiographs, as attempts to mark it in other projections face many limitations. Full article

This systematic review synthesized all randomized controlled trials (RCTs) and controlled trials examining the effects of wearable health technology-based physical activity interventions on physiological, cognitive, and emotional outcomes in breast cancer survivors (BCS). We searched NCBI, Academic Search Premier, EMBASE, Web of Science, PubMed, and Medline from inception to March 2021. We included studies which: (1) were RCTs or controlled trials ≥8 weeks in duration; (2) were peer-reviewed and published in English; (3) sampled BCS in full remission and had not received treatment for at least six months; (4) utilized wearable health technology (e.g., Fitbit, Garmin xGC30); and (5) examined physiological, emotional, and/or cognitive outcomes. Sixty-six studies were identified and 14 were included in the review. Most of the observed effects were statistically significant and those which employed multi-component interventions generally yielded greater effects. Overall, the use of wearable health technology reduced sedentary behavior and increased moderate-to-vigorous intensity physical activity. Further, increased moderate-to-vigorous intensity physical activity was observed to be associated with increased perceived cognition and higher cognitive performance. Multiple studies also observed significant improvements in attitude, worry, and anxiety. Overall, findings suggested wearable health technology-based physical activity interventions to be effective for improving physical activity, attitude, and cognitive functions and for reducing sedentary behavior, anxiety, and worry in BCS. Full article