J. Clin. Med., Volume 12, Issue 23 (December-1 2023) – 306 articles

Histamine intolerance arises when there is a disparity between the production of histamine and the body’s ability to break it down. In the gastrointestinal tract, the primary enzyme responsible for metabolizing ingested histamine is diamine oxidase (DAO), and a shortage of this enzyme has been associated with some diseases related to the respiratory, cardiovascular, nervous, muscular, and digestive systems, in addition to migraines. The treatment of migraines typically revolves around the utilization of both anti-migraine and anti-inflammatory drugs, but their interaction with DAO is not thoroughly understood. In this study, we examined the impact of nonsteroidal anti-inflammatory drugs (NSAIDs) and anti-migraine medications on DAO activity through in vitro experiments. We also investigated their effects on the human intestinal cell line Caco-2, assessing changes in DAO expression (both at the mRNA and protein levels) as well as DAO activity. The tested drugs, including ibuprofen, acetylsalicylic acid, paracetamol, a combination of acetylsalicylic acid with paracetamol and caffeine, zolmitriptan, and sumatriptan, did not inhibit DAO activity or reduce their levels. However, naproxen reduced DAO protein levels in human enterocyte cultures while not affecting DAO activity. These results suggest that combining anti-inflammatory and anti-migraine drugs with DAO enzyme supplementation for migraine patients with DAO deficiency could be beneficial for healthcare professionals in their daily practice. Full article

Incidental pulmonary nodules detected via computed tomography (CT) are usually small, solid nodules (diameters less than 8 mm) that are likely benign and are difficult to biopsy. Additional features of the benignity of these small nodules may help determine the need and periodicity of further follow-up and should be identified. This study was conducted to examine the clinical factors associated with benign solid pulmonary nodules measuring less than 8 mm in diameter. This retrospective study enrolled participants who underwent low-dose chest CT scans for 3 consecutive years during routine health check-ups at a university hospital in Korea. We chose a 2-year study period to ensure that the nodule(s) were benign, which meant there was no interval change over this period. Participants were stratified into two groups: no nodule (n = 56) and nodule(s) (n = 355). Multivariable logistic regression analyses were performed to explore associations (adjusted odds ratio [aOR], 95% confidence interval [CI], p-value) between variables and nodule(s). In this study cohort, elevated levels of low-density lipoprotein (LDL) cholesterol were positively associated factors with the presence of benign pulmonary nodule(s) (aOR: 1.10, 95% CI:1.00–1.20, p = 0.0488), whereas current cigarette smoking was negatively associated with nodules (aOR: 0.26, 95% CI: 0.08–0.81, p = 0.0202). Therefore, an elevated LDL cholesterol level was the only factor that was positively associated with the presence of benign small pulmonary nodules. Full article

Consideration for oversizing the proximal stent graft is suggested in endovascular aortic repair. However, a special recommendation for the proximal oversizing ratio (OSR) in patients with ruptured abdominal aortic aneurysm (rAAA) is ambiguous. This study aims to evaluate the effect of different degrees of the proximal oversizing ratio (OSR) on risk of type IA endoleak (TIAEL) in hemodynamically stable and unstable patients with rAAA undergoing emergency endovascular aortic repair (EVAR). Our study included 134 rAAA patients undergoing emergent EVAR, and we did not observe a significant association between hemodynamic instability and risk of T1AEL (HR 3.89, 95%CI 0.40–37.75, p = 0.24). All three T1AELs in the hemodynamically unstable subgroup were observed in patients with OSR ≤ 30%, but no significant difference was found regarding T1AEL between patients with OSR > 30% and OSR ≤ 30% (0.00% vs. 11.11%, p = 0.19). As for hemodynamically stable patients, OSR > 20% was associated with a significantly decreased risk of T1AEL (HR 0.03, 95%CI 0.01–0.53, p = 0.016). In conclusion, a proximal OSR > 20% is associated with a decreased risk of T1AEL in hemodynamically stable patients, while an OSR > 30% did not add an additional advantage of lowering the risk of T1AEL in hemodynamically unstable patients. Full article

Ultra-low contrast percutaneous coronary interventions (ULPCIs) are a novel field of interventional cardiology, aiming to reduce the risk of contrast-induced nephropathy (CIN), which is a well-described adverse event after angiography. CIN is a well-described adverse event following PCI, especially in high-risk patients, i.e., patients with an already deteriorating renal function or chronic kidney disease, as well as patients of advanced age or requiring an increased amount of contrast during their intervention. Among the techniques described for ULPCI procedures, intravascular imaging guidance seems a promising option, as it allows lesion recognition and characterization, stent implantation, and PCI optimization. Intravascular ultrasound (IVUS) is the modality most commonly used, as it does not require contrast injection, contrary to optical coherence tomography (OCT). Several clinical trials, assessing IVUS in the context of ULPCI, have shown that it can be safely used in this setting while offering a substantial reduction in contrast media volume, as well as renal adverse outcomes. This review aims to describe the need for ULPCI and technical considerations regarding the use of intravascular imaging in this setting, as well as analyze the available evidence from clinical trials regarding the safety and efficacy of IVUS-ULPCI, in order to provide a comprehensive summary for practicing physicians. Full article

Background: Patients with infectious complications related to the presence of cardiac implantable electronic devices (CIED) constitute a heterogeneous group, ranging from local pocket infection (PI) to lead-related infectious endocarditis (LRIE) infection spreading along the leads to the endocardium. The detection of isolated LRIE and the assessment of the spread of infection in a patient with PI is often difficult and requires complex imaging and microbiological tests. The aim of the current study is to evaluate the usefulness of new simple hematological parameters in detecting infectious complications in patients with CIED, differentiating vegetation and vegetation-like masses, and assessing the extent of infections in patients with PI. Methods: A retrospective analysis of clinical data of 2909 patients (36.37% with CIED-related infections), undergoing transvenous lead extraction (TLE) procedures in three high-volume centres in the years 2006–2020, was conducted. Receiver operating characteristic (ROC) curve analysis was used to assess the sensitivity and specificity of neutrophil-to-lymphocyte ratio (NLR), neutrophil-to-platelet ratio (NPR), and lymphocyte-to-platelet ratio (LPR) in the diagnosis of CIED infections, evaluate the spread of the infectious process in patients with PI and differentiate additional structures related to the presence of lead. Results: The values of NLR and NPR were significantly higher in infectious patients than non-infectious controls (3.07 vs. 2.59; p < 0.001, and 0.02 vs. 0.01; p = 0.008) and the area under the ROC curve (AUC) was 0.59; p < 0.001 and 0.56; p < 0.001, respectively. The high specificity of the new markers in detecting the infectious process was demonstrated: 72.82% for NLR (optimal cut-off value: 3.06) and 79.47% for NPR (optimal cut off value: 0.02). The values of NLR and NPR were significantly higher in patients with vegetations than in non-infectious patients with the presence of additional lead-related masses (3.37 vs. 2.61; p < 0.001 and 0.03 vs. 0.02; p = 0.008). The AUC of NLR and NPR for the prediction of vegetations was 0.65; p < 0.001 and 0.60; p < 0.001 with the highest specificity of NPR (82.78%) and an optimal cut-off value of 0.03. NLR and NPR were higher in patients with LRIE compared to isolated PI (4.11 vs. 2.56; p < 0.001 and 0.03 vs. 0.02; p < 0.001) and the ROC curve analysis for coexistence LRIE with PI showed the AUC for NLR: 0.57; p < 0.001 and AUC for NPR: 0.55; p = 0.001. High specificity in the detection of coexistence between PI and LRIE was demonstrated for NLR (87.33%), with an optimal cut-off value of 3.13. Conclusions: Novel hematological markers (NLR and NPR) are characterized by high specificity in the initial diagnosis of CIED infections, with optimal cut-off values of 3.06 and 0.02. NLR is also useful in the assessment of the spread of infection in patients with PI, with a calculated optimal cut-off value of 3.13. NPR may be helpful in the differentiation of vegetation and vegetation-like masses with an optimal cut-off value of 0.03. Full article

There is a wide variety of tools and measures for rehabilitation outcomes in post-stroke patients with impairments in the upper limb and hand, such as paralysis, paresis, flaccidity, and spasticity. However, there is a lack of general recommendations for selecting the most appropriate scales, tests, and instruments to objectively evaluate therapy outcomes. Reviews on upper limb and hand measurements reveal that clinicians’ choices of tools and methods are highly varied. Some clinicians and medical teams continue to employ non-standard and unverified metrics in their research and measurements. This review article aims to identify the key parameters, assessed by outcome measures and instruments, that play a crucial role in upper limb and hand rehabilitation for post-stroke patients, specifically focusing on the recovery of hand function. The review seeks to assist researchers and medical teams in selecting appropriate outcome measures when evaluating post-stroke patients. We analyze the measured factors and skills found in these outcome measures and highlight useful tools that diversify assessments and enhance result objectivity through graphical representation. The paper also describes trends and new possibilities in hand outcome measures. Clinicians frequently use proven devices, such as EMG, goniometers, and hand dynamometers. Still, there is a growing trend towards incorporating technologies, such as pose and position estimation, using artificial intelligence, or custom hand grip measurement devices. Researchers are increasingly adopting scales previously successful in orthopedic and surgical patients, recognizing their potential for objectivizing outcomes in neurological patients with post-stroke hand complications. The review included only adults over the age of 18. Outcome measures were tested for usefulness in the rehabilitation of stroke patients. Full article

(1) Background: Liver transplantation (LT) is associated with significant hemorrhage and massive transfusions. Fibrinogen replacement has a key role in treating massive bleeding during LT and hypofibrinogenemia is treated by fibrinogen concentrate or cryoprecipitate. However, these two products are known to be associated with major thromboembolism events (MTEs). We aimed to compare the effect of fibrinogen concentrate and cryoprecipitate on MTEs in living donor LT (LDLT) recipients. (2) Methods: We analyzed 206 patients who underwent LDLT between January 2021 and March 2022. The patients were divided into two groups according to fibrinogen concentrate or cryoprecipitate use. We compared the incidence of MTEs between the two groups. In addition, we performed multiple logistic regression analyses to identify the risk factors for MTEs. (3) Results: There was no significant difference in the incidence of MTEs (16 [14.7%] vs. 14 [14.4%], p = 1.000) between the cryoprecipitate group and fibrinogen concentrate group. In the multivariate analysis, cryoprecipitate (OR 2.09, 95%CI 0.85–5.11, p = 0.107) and fibrinogen concentrate (OR 2.05, 95%CI 0.82–5.12, p = 0.126) were not significantly associated with MTEs. (4) Conclusions: there was no significant difference in the incidence of MTEs between cryoprecipitate and fibrinogen concentrate in LDLT recipients. Full article

Data on the real long-term influences of in utero drug exposure in pregnant women on childhood development are scarce and remain not well determined and depend on the duration of in utero drug exposure and maternal drug levels. Therapeutic drug monitoring (TDM) during pregnancy may help limit fetal drug exposure while maintaining an effective dose for the treatment of the underlying inflammatory bowel disease (IBD) in women. Most antibody therapies used in patients with IBD are IgG molecules which are actively transported across the placenta, especially during the third trimester of the pregnancy. Here, we propose an up-to-date clinical review to summarize the available findings of serum drug levels in maternal blood during pregnancy, in the cord blood, infants at delivery and in breast milk of patients with IBD treated with biologics. Conversely, in comparison to adalimumab (ADA) levels, which are relatively stable during pregnancy, infliximab (IFX) drug clearance decreased significantly during the last two trimesters of the pregnancy, leading to increasing drug concentrations in the blood of the pregnant women. As most guidelines recommend using live vaccines in infants at the age of one or earlier in case of negative serum drug levels in newborns, statistical models could help clinicians in making a decision to adjust the last dose of the biologic during pregnancy and to determine the optimal date to vaccinate. Altogether, data from the literature offers strong reassurance in terms of safety for anti-TNFα therapies during pregnancy not only for IBD patients who intend to conceive, but also for pregnant women and for the physicians taking care of these patients. ADA and IFX levels in breast milk are detectable, but at very low levels, and therefore, it is recommended to pursue breast feeding under anti-TNFα therapy. Our knowledge on ustekinumab or vedolizumab levels in pregnant women remains unclear and scarce. These drugs are currently not recommended for patients with IBD in clinical practice. Therefore, TDM and proactive dose adjustment are not necessary during pregnancy since its impact on making a clinical decision have not yet been clearly demonstrated in routine practice. Overall, drug concentrations in the cord blood, an infant at birth and postpartum serum concentrations in infants, due to active placental drug transfer, may have a greater impact than the limited drug transfer in breast milk during lactation on the risk of infection and developmental outcomes. Ustekinumab and vedolizumab exposure during pregnancy and lactation are both considered low risk by the recent ECCO guidelines despite the limited data that are currently available. Full article

Anorectal manometry is one of the most frequently performed gastrointestinal motility studies in children. It is an important study in diagnosing Hirschsprung disease (HD). These procedures can be uncomfortable, painful and emotionally distressing. Nitrous oxide or midazolam are the only pharmacologic options available, as clinical experience suggests that they do not alter manometry readings. Our study was designed to determine whether Dexmedetomidine (DEX) could provide adequate sedation without disrupting anal and rectal pressure. The effect of DEX on anorectal function has never been studied in children. This prospective study recorded anorectal manometry (ARM) measurements prior to the administration of DEX and then repeated the measurements at 1 and 5 min after DEX. The main ARM measurements included resting intra-anal sphincter pressure (IASP) and the presence and characteristics of the recto-anal inhibitory reflex (RAIR). DEX was administered as a bolus followed by a continuous infusion. Twenty patients were included (60% female; mean age 10.8 ± 4.6 years). The RAIR became absent in 2/16 (12.5%) patients after DEX administration. DEX may alter physiologic ARM and IASP recordings necessary to diagnose gastrointestinal medical conditions. Full article

Background: Hearing loss caused by middle ear malformations is treated by tympanoplasty to reconstruct the acoustic conduction system. The mobility of the ossicles plays a crucial role in postoperative success. However, identifying the location of ossicular malformation based solely on preoperative audiograms is challenging due to the complex relationship between fixation location, deformity levels, and ossicular mobility. Methods: Middle ear finite element models for simulating ossicular malformations were created, and the results were compared with the actual preoperative audiograms. Results: This approach objectively diagnosed ossicular fixation and disarticulation, bypassing traditional criteria reliant on physician examination or imaging. Conclusion: This study suggests that future research should focus on developing a diagnostic framework utilizing large-scale data. Full article

Cardiovascular diseases are a group of disorders of heart and blood vessels which are the leading cause of death globally. They are also a very important cause of military unsuitability especially among military pilots. Some of the risk factors cannot be modified, but a large group of them can be modified by introducing healthy habits or behaviors, such as regular physical activity, quitting of tobacco smoking, cessation of harmful alcohol consumption, or stress avoidance. Specific occupational and environmental factors, such as acceleration, pressure changes, hypoxia, thermal stress, noise, vibration, prolonged sedentary posture, difficulties in moving the limbs, shifts, work shift irregularities, circadian dysrhythmia, variations in the microclimate, motion sickness, radiation, toxicological threats, occupational stress, emotional tension, highly demanding tasks especially during take-off and landing, predominance of intellectual over physical activity, and forced operation speed against time shortage are considered as characteristic for military personnel, especially military aircrews. They are of special concern as some of them are considered as potential CVD risk factors. The aim of this study was to discuss the influence of selected occupational and environmental factors (noise, altitude, hypoxia, acceleration forces, tobacco smoking, oral health, and stress) regarding their importance for CVD risk in military professionals and military aviators. The performed revision confirmed that they are exposed to certain characteristic conditions, which may influence the CVD risk but the number of solid scientific data regarding this subject are limited. There is a great need to perform complex studies on environmental and occupational risk factors for CVDs in military personnel and military aviators as well as how to minimize their influence to prolong the state of health and military suitability of this professional groups. Full article

Background: Pregnancy, a complex biological phenomenon, relies on intricate maternal–fetal interactions for success. Decidual natural killer (dNK) cells and trophoblasts are pivotal in establishing immune tolerance at the maternal–fetal interface. The chemokine receptor CXCR4 plays a crucial role in NK cell development and immune tolerance during early placental development. Methods: Primary decidual immune cells from 42 women with normal pregnancies and 20 patients experiencing recurrent spontaneous abortions (RSAs) were studied. Gene transcription in NK cells was assessed using real-time polymerase chain reaction. In a co-culture system, we examined the influence of trophoblasts on CXCR4 expression in dNK cells, with subsequent analysis conducted via flow cytometry. The proportion of CXCR4⁺ NK cells was assessed using flow cytometry after co-culture with trophoblasts pre-treated with 3-MA or a p53 activator. Results: Our study confirmed a diminished presence of decidual CXCR4⁺ NK cells in RSA patients during early pregnancy. Co-culturing with a trophoblast-derived supernatant increased CXCR4 expression in dNK cells. In addition, trophoblast autophagy plays an educative role in regulating the dNK landscape via the IGF2-TP53-CXCR4 axis. Conclusion: Autophagy inhibition in trophoblasts induces an aberrant shift in the CXCR4⁺ dNK phenotype, potentially contributing to pregnancy loss. This sheds light on the nuanced behavior of dNK cells during pregnancy, offering promising therapeutic avenues to mitigate pregnancy complications. Full article

Hidradenitis suppurativa (HS) is a chronic skin disease that can have an association with endocrine disorders. There is conflicting information in the literature regarding the role of the thyroid gland in HS. This study aimed to close this knowledge gap and investigate how thyroid disease is involved in patients with HS. We carried out a case–control study with a total of 160 patients, of whom 108 were patients with HS and 52 were controls matched for age and sex. Parametric and non-parametric methods were used to analyze the results. We calculated structural parameters of thyroid homeostasis to detect subclinical thyroid disease, non-thyroid disease syndrome and other forms. The severity of HS was not associated with thyroid hormone levels and antibodies (p > 0.05). HS patients with or without hypothyroidism had decreased FT4 levels and a decreased thyroid secretory capacity (SPINA-GT). Titers of TSH receptor autoantibodies (TRAb) were significantly higher in smoking HS patients compared to non-smokers (median: 1.18 vs. 1.08; p = 0.042). The rate of subclinical hypothyroidism was significantly higher in HS patients; thus, subclinical hypothyroidism is an important comorbidity of HS (p < 0.05). Further studies are needed to investigate whether the chronic inflammation of HS is a cause of increased rates of (subclinical) hypothyroidism. Full article

Chronic low back pain (CLBP) is a significant public health issue, with prevalence intensifying due to an ageing global population, amassing approximately 619 million cases in 2020 and projected to escalate to 843 million by 2050. In this study, we analyzed the effects of multidisciplinary biopsychosocial rehabilitation (MBR) on pain and disability. To address this question, we conducted a PRISMA-guided systematic review and random-effect network meta-analysis on studies collected from six electronic databases. The network comprised diverse MBR modalities (behavioral, educational, and work conditioning) alongside exercise therapy (ET), minimal intervention, and usual care, with pain and disability as outcomes. Ninety-three studies were included, encompassing a total of 8059 participants. The NMA substantiated that both ET and MBR modalities were effective in alleviating CLBP, with education-oriented MBR emerging as the most efficacious for pain mitigation (MD = 18.29; 95% CI = 13.70; 22.89) and behavior-focused MBR being the most efficacious for disability reduction (SMD = 0.88; 95% CI = 0.46; 1.30). Nevertheless, the discerned differences amongst the treatments were minimal and uncertain, highlighting that no modality was definitively superior to the others. Given the intricate nature of CLBP, embodying various facets, our findings advocate for a combined therapeutic approach to optimize treatment efficacy. Full article

Electromagnetic radiation, notably visible light (VL), has complicated effects on human skin, particularly pigmentation, which have been largely overlooked. In this review, we discuss the photobiological mechanisms, pathological effects, clinical applications and therapeutic strategies of VL at varying wavelengths on melanocyte biology and skin pigmentary disorders. Different VL wavelengths may impose positive or negative effects, depending on their interactions with specific chromophores, photoaging, ROS production, circadian rhythm and other photon-mediated reactions. Further in vivo and in vitro studies are required to establish the pathologic mechanisms and application principles of VL in pigmentary disorders, as well as optimal photoprotection with coverage against VL wavelengths. Full article

We evaluated the effectiveness of early direct oral anticoagulant (DOAC) monotherapy within one year after percutaneous coronary intervention (PCI) in patients with atrial fibrillation (AF) using Korean National Health Insurance Service data. AF patients who underwent PCI were included and divided into the DOAC monotherapy group and the combination therapy group (DOAC with an antiplatelet agent) based on the medications used at 6 months after PCI. A major adverse cardiovascular event (MACE) was defined as a composite of cardiovascular death, acute myocardial infarction (AMI), stroke, or systemic thromboembolic event between 6 and 12 months after PCI. In the overall study population, the DOAC dose reduction rate was high in both the monotherapy group (70.8%) and the combination therapy group (79.1%). After propensity score matching, the MACE incidence was not significantly different between the two groups (hazard ratio [HR] 1.42 [0.90–2.24]). The numerical trend for higher MACE in the monotherapy group was mainly driven by the difference in stroke incidence (HR 1.84 [0.97–3.46]). All-cause death (HR 1.29 [0.61–2.74] or the incidence of major bleeding (HR 1.07 [0.49–2.35]) results were similar in the two groups. In conclusion, early DOAC monotherapy was not significantly associated with MACE risk between 6 and 12 months after PCI. Full article

Vitiligo, the most prevalent skin depigmenting disease, is characterized by the selective loss of melanocytes, impacting patients’ quality of life significantly. This autoimmune disorder progresses through a complex interplay of genetic and non-genetic factors, posing challenges in comprehending its pathogenesis and devising effective treatment strategies for achieving remission. Existing conventional therapeutic approaches, such as topical and oral corticosteroids, calcineurin inhibitors, and phototherapy, lack specificity, offer modest efficacy, and may entail potential adverse effects. Consequently, there is a pressing need for a more nuanced understanding of vitiligo’s pathogenesis to pave the way for targeted therapeutic innovations. This review aims to provide a comprehensive overview of recent developments and findings concerning Januse Kinase (JAK) inhibitors and biologics tested in vitiligo patients. JAK inhibitors have exhibited promising results, showcasing both efficacy and tolerability. In contrast, the outcomes of biologics treatment have been more varied. However, to establish a clearer understanding of which specific pathways to target for a more effective approach to vitiligo, additional in vitro studies and extensive clinical research involving a larger population are imperative. Full article

The incidence of pancreatic ductal adenocarcinoma (PDAC) is rising. While surgical techniques and peri-operative care have improved, the overall survival for PDAC remains poor. Thus, novel and bold research initiatives are needed along the spectrum of clinical care, a few of which will be discussed in this article. Early detection is crucial, with specific high-risk groups possibly benefiting from targeted screening programs. Liquid biopsies (such as circulating exosomes, tumor DNA, or tumor cells) offer promise as multifunctional biomarkers for early detection, treatment guidance, and recurrence monitoring. Precision medicine is being explored via targeted therapies for actionable mutations, such as PARP inhibitors for BRCA mutations, and immunotherapy strategies. Artificial intelligence (AI) is emerging as a powerful tool in medical imaging, biomarker discovery, genetics research, and treatment planning, and it can aid in diagnosis, treatment selection, and patient monitoring. However, its associated challenges include ethics, data security, algorithm reliability, and validation. Collaborative efforts between medical professionals, researchers, and AI experts are vital for unlocking AI’s potential to enhance pancreatic cancer care. In conclusion, despite the challenges, advancements in liquid biopsies, precision medicine, and AI offer hope for enhancing the diagnosis, treatment, and management of pancreatic cancer. Full article

Background: Dry eye disease (DED) is a common chronic condition with increasing prevalence. Standard discriminative visual acuity is not reflective of real-world visual function, as patients can achieve normal acuities by blinking. Methods: Participants recruited from a tertiary referral eye centre were divided into two groups—Severe DED (with significant, central staining) and Mild DED (absence of such staining). Functional Visual Acuity (FVA) in both groups was assessed using the DryeyeKT mobile application and Impact of Vision Impairment (IVI) questionnaire to assess quality of life (QOL). Results: Among the 78 participants (74.4% women), 30 (38.5%) had Severe DED and 48 (61.5%) Mild DED. In women, Severe DED produced a significantly worse FVA of 0.53 ± 0.20 vs. 0.73 ± 0.30 in the Mild DED group (p = 0.006). FVA decreased with increasing age, showing a significant inverse correlation (r = −0.55). A poorer FVA ≤ 0.6 was seen in older patients (68.2 years ± 7.68) vs. an FVA > 0.6 in younger patients (58.9 years ± 10.7), p < 0.001. When adjusting for age, FVA was still 0.107 lower in the Severe DED group, p = 0.003. There was significant difficulty in performing specific daily activities in the Severe DED group, after adjusting for age, gender and FVA. Conclusions: FVA is reduced in severe DED and older people. Severe DED significantly impacts certain aspects of QOL. However, no significant relationship was found between FVA and QOL. FVA is not the only reason for the compromise of health-related QOL in severe dry eye. Full article

Sarcopenia is as a non-traditional risk factor for atherosclerotic cardiovascular disease. Further investigation is required to elucidate the prognostic significance of computed tomography (CT)-based sarcopenia assessment in coronary artery disease (CAD). We prospectively enrolled 475 patients, who underwent coronary stent implantation and peri-procedural CT scans within one month. Skeletal muscle index (SMI) was assessed cross-sectionally at the first lumbar vertebra (L1) level. The participants were grouped based on sex-specific L1 SMI quartiles. The primary endpoint was all-cause mortality, and the secondary composite endpoint was major adverse cardiovascular events (MACEs) over a 3-year follow-up period. Three-year all-cause mortality and MACE incidence increased significantly in patients in the lower L1 SMI quartiles compared to those of patients in the higher quartiles (p < 0.001). The individual composite endpoints consistently showed a higher incidence in the lower quartiles of L1 SMI (p < 0.001). In multivariable analysis, the lower L1 SMI quartiles independently predicted 3-year all-cause mortality and MACEs (lowest vs. highest quartiles, respectively: OR 4.90 (95% CI 1.54–15.5), p = 0.007; and OR 12.3 (95% CI 4.99–30.4), p < 0.001). In conclusion, CT-based L1 SMI demonstrated a distinct dose-dependent relationship with future MACEs in CAD patients undergoing percutaneous coronary intervention, thereby enhancing cardiovascular risk stratification. Full article

Chronic spontaneous urticaria (CSU) is when lesions occur for ≥6 weeks. However, its underlying mechanism remains unclear. CSU prevalence is similar in adult and pediatric patients; nevertheless, few data are available on CSU characteristics in pediatric patients. We aimed to describe the epidemiology, clinical features, and treatment approach of CSU in pediatrics and adults. In this cross-sectional study, 193 patients with CSU were treated at the Sheba Medical Center, Israel, in 2009–2022. The information collected includes age at diagnosis, reported triggers, atopic co-morbidities, autoimmune co-morbidities, treatments and their response, family background, laboratory tests, and follow-up duration. The study group was divided into pediatrics (aged ≤ 18) and adults. Metabolic syndrome was most prevalent in adults as against atopy in pediatrics. Autoimmune co-morbidities were observed in 34.7% and 34.8% of adults and pediatrics, respectively. Inflammatory bowel disease and thyroid disease were the most common in pediatrics and adults, respectively. Systemic treatments other than antihistamines were administered more frequently in adults. Adults with autoimmune disease required second-line treatment with immunomodulators compared to those without it. Co-morbidities were more common in adults than in pediatrics. Patients with autoimmune co-morbidities may be more challenging to manage; thus, escalation to biologics should be considered soon. Full article

Interstitial lung disease (ILD) frequently complicates mixed connective tissue disease (MCTD) and contributes to increased mortality. We aimed to identify predictors of ILD in MCTD patients. This is a nationwide, multicentre, retrospective study including patients with an adult-onset MCTD clinical diagnosis who met Sharp’s, Kasukawa, Alarcón-Segovia, or Kahn’s diagnostic criteria and had available chest high-resolution computed tomography (HRCT) data. Univariate and multivariate analyses were conducted. We included 57 MCTD patients, with 27 (47.4%) having ILD. Among ILD patients, 48.1% were asymptomatic, 80.0% exhibited a restrictive pattern on pulmonary function tests, and 81.5% had nonspecific interstitial pneumonia on chest HRCT. Gastroesophageal involvement (40.7% vs. 16.7%, p = 0.043) and lymphadenopathy at disease onset (22.2% vs. 3.3%, p = 0.045) were associated with ILD. Binary logistic regression identified lymphadenopathy at disease onset (OR 19.65, 95% CI: 1.91–201.75, p = 0.012) and older age at diagnosis (OR 1.06/year, 95% CI: 1.00–1.12, p = 0.046) as independent ILD predictors, regardless of gender and gastroesophageal involvement. This study is the first to assess a Portuguese MCTD cohort. As previously reported, it confirmed the link between gastroesophageal involvement and ILD in MCTD patients. Additionally, it established that lymphadenopathy at disease onset and older age at diagnosis independently predict ILD in MCTD patients. Full article

Inborn errors of immunity (IEIs) are a heterogeneous group of diverse clinical and genetic phenotypes that have an estimated combined prevalence as high as 1/1000. Increased risk of frequent, severe, or opportunistic infections is a common feature of IEIs, but there are also diverse immune-mediated, non-infective complications that are associated with significant morbidity and mortality. As patient survival increases, these are becoming more apparent within the liver. Hepatic involvement of IEIs may not only manifest as infections, but also nodular regenerative hyperplasia, granulomatous disease, autoimmune hepatitis and malignancy. As therapeutic options for patients are expanding, with both pharmaceutical treatments as well as haematopoietic stem cell transplant (HSCT), iatrogenic liver injury is increasingly common and important to identify. This review article summarises the spectrum of hepatic complications seen in IEIs, and highlights the challenges of management within this patient cohort, where immunosuppression is poorly tolerated. Early recognition and prompt diagnosis of potential hepatic complications is therefore crucial in ensuring potentially reversible causes are treated, but significant uncertainty remains regarding best practice for many features of immune dysregulation with limited high-quality evidence. Full article

Retinal vein occlusion (RVO) results in ischemia followed by an inflammatory response. Both processes affect tissue temperature in opposite directions. Here, we evaluate the effect of RVO on the ocular surface temperature (OST) profile. Subjects with RVO were prospectively recruited. Healthy subjects without any ocular disease served as controls. The OST was determined using the Therm-App thermal imaging camera, and image processing software was employed to compute the mean temperature values of the medial canthus, lateral canthus, and cornea. We obtained thermographic images from 30 RVO subjects (30 eyes) and 148 controls (148 eyes). A univariate analysis found that eyes with RVO had significantly elevated OSTs compared to the controls (mean difference of 0.6 ± 0.3 Celsius, p < 0.05). However, this distinction between the groups lost statistical significance upon adjusting for possible confounders, including patient and environmental factors. These findings were confirmed with a post hoc case–control matched comparison. In conclusion, RVO does not seem to affect the OST. This might be due to the balance between inflammatory thermogenesis and heat constriction from ischemia in RVO. It is also possible that, in our cohort, the RVO pathophysiological processes involved were localized and did not extend to the anterior segment. Patient and environmental factors must be considered when interpreting the OST. Full article

Background: Foot deformities in children are common, and the majority can be treated conservatively. Nevertheless, there are deformities that require surgical treatment. These include rigid clubfeet, severe forms of pes planovalgus, pes cavus and several more. We retrospectively analysed the pseudarthrosis rate of surgical treatment of foot deformities with transcutaneous K-wire osteosynthesis in neurologically healthy children and adolescents. The aim of the study was to show that the results with K-wires are comparable to those with other osteosynthesis methods in the literature. Methods: A total of 46 paediatric patients aged 6 to 17 years treated between January 2010 and December 2015 met the inclusion criteria. Depending on the diagnosis, different surgical interventions were necessary. In clubfoot and pes planovalgus, representing n = 81, 70% of the whole collective triple arthrodesis with fusion of the talonavicular, calcaneocuboid and subtalar joints or Evans osteotomy was usually performed. Radiographs were taken at least 6 months post-surgery, and bony consolidation of the subtalar, talonavicular (TN), and calcaneocuboidal (CC) joints and the metatarsal I (MT I) osteotomy were assessed. If there was no evidence of fusion at this time, it was considered non-union. Results: In total, 117 arthrodesis procedures with K-wires were performed. Overall, 110 of the arthrodesis (94%) healed, and only 7 joints (6%) showed non-union (subtalar 0%, TN 7.7%, CC 6.5% and MT I 6.7%). All non-unions occurred in subjects with clubfoot deformities. No significant risk factors were observed. Conclusion: This study replicated the good consolidation rates reported in the literature with screws, plates, intramedullary nails or staples in arthrodesis of the adolescent foot in neurologically healthy subjects and confirmed the efficacy of K-wires. The main advantages of transcutaneous K-wire treatment are easy metal removal, lower osteosynthesis material costs and less concomitant damage. Further studies, especially randomised controlled trials, are needed to further investigate this topic. Full article

Background: Arteriovenous (AV) loops help to overcome absent or poor-quality recipient vessels in highly complex microvascular free flap reconstruction cases. There are no studies on blood flow and perfusion patterns. The purpose of this study was to evaluate and compare intraoperative hemodynamic characteristics of AV loops followed by free tissue transfer for thoracic wall and lower extremity reconstruction. Methods: this prospective clinical study combined Transit-Time Flowmetry and microvascular Indocyanine Green Angiography for the assessment of blood flow volume, arterial vascular resistance and intrinsic transit time at the time of AV loop construction and on the day of free flap transfer. Results: A total of 11 patients underwent AV loop creation, of whom five required chest wall reconstruction and six required reconstruction of the lower extremities. In seven of these cases, the latissimus dorsi flap and in four cases the vertical rectus abdominis myocutaneous (VRAM) flap was used as a free flap. At the time of loop construction, the blood flow volume of AV loops was 466 ± 180 mL/min, which increased to 698 ± 464 mL/min on the day of free tissue transfer (p > 0.1). After free flap anastomosis, the blood flow volume significantly decreased to 18.5 ± 8.3 mL/min (p < 0.001). There was no significant difference in blood flow volume or arterial vascular resistance between latissimus dorsi and VRAM flaps, nor between thoracic wall and lower extremity reconstruction. However, a significant correlation between the flap weight and the blood flow volume, as well as to the arterial vascular resistance, was found (p < 0.05). Conclusion: This is the first study to perform intraoperative blood flow and hemodynamic measurements of AV loops followed by free tissue transfer. Our results show hemodynamic differences and contribute to deeper understanding of the properties of AV loops for free flap reconstruction. Full article

Background. Hemoglobinopathies, among which thalassemic syndromes (transfusion-dependent and non-transfusion dependent thalassemias) and sickle cell disease (SCD), are the most widespread monogenic diseases worldwide. Hemoglobinopathies are endemic and spread-out all-over Italy, as result of internal and external migration flows. Nowadays, the increase therapeutic options associated to the general aging of patients with hemoglobinopathies related to the improvement in clinical management, contribute to the abnormalities in kidney function going from blood and urine test alterations to chronic kidney disease and end stage renal disease. Methods. Here, we carried out a revision of the literature as panel of recognized experts in hemoglobinopathies with the consultancy and the revision of two nephrologists on kidney alteration and kidney disease in patients with TDT, NTDT and SCD. This is part of the action of the Italian society for the study of thalassemia and hemoglobinopties (SITE). The purpose of this “good practice (GP)” is to provide recommendations for follow-up and therapy for the management of kidney alterations in patients with TDT, NTDT and SCD. The literature review covers the period 1.1.2016 to 31.12.2022. In consideration of the rarity of these diseases, the analysis was extended from 5 to 7 years. Moreover, in the absence of relevant scientific papers in the identified time frame, we referred to pivotal or population studies, when available. Finally, in the absence of evidence-based data from prospective and randomized trials, the authors had to refer to expert opinion (expert consensus) for many topics. Results. We generated question and answer boxes to offer a friendly consultation, using color code strategy and focused answers. Conclusions. The present GP will help in improving the clinical management, and the quality of care of patients with hemoglobinopathies. Full article

Background: Pes planovalgus, or flexible flatfoot, deformity is a common problem in pediatric orthopedic patients. There is no consensus on using the technique of arthroereisis in the treatment of symptomatic pes planovalgus. The aim of our study was to prospectively assess the functional outcomes following symptomatic pes planovalgus treatment with the use of the Spherus talar screw. Methods: Twenty-seven patients (11 females, 16 males), at a mean age of 10.5 years (7–14 years) were included in the prospective study. We assessed the level of physical activity (including sports) based on the University of California, Los Angeles (UCLA) activity scale, a 10-point level-of-activity VAS scale, and the Grimby physical activity scale. Pain was assessed based on a VAS pain scale; foot function was assessed with the revised Foot Function Index (FFI-R); and ankle joint mobility was measured. Results: The mean follow-up period was 18 months (14–26 months). There was a significant improvement in VAS-measured physical activity scores from 5.47 to 7 at follow-up, p = 0.048. There was a significant improvement in UCLA activity scale scores from 4.78 to 6.05 at follow-up, p = 0.045. Pain levels decreased from a mean VAS score of 4.73 prior to surgery to a mean score of 2.73 at follow-up, p = 0.047. The functional FFI-R scores showed a significant improvement from 140 points prior to surgery to 97.75 points at follow-up, p = 0.017. Comparison of the preoperative and follow-up values of the range of plantar flexion, adduction, and abduction in the operated limb also showed no significant changes in those individual parameters. The mean values of dorsiflexion, plantar flexion, adduction, and abduction at the ankle joint at follow-up, compared individually between the operated and non-operated foot showed no statistically significant differences. Conclusions: The use of a talar screw in the treatment of symptomatic pes planovalgus helps reduce pain and improve functional outcomes after treatment. Foot function assessments showed diminished pain, improved levels of physical and sport activity, and no effect on the range of motion after surgery in comparison with preoperative data. Arthroereisis with a talar screw is a valid surgical technique for the treatment of symptomatic pes planovalgus. Full article

Antibodies directed against donor-specific human leukocyte antigens (HLAs) can be detected de novo after heart transplantation and play a key role in long-term survival. De novo donor-specific antibodies (dnDSAs) have been associated with cardiac allograft vasculopathy, antibody-mediated rejection, and mortality. Advances in detection methods and international guideline recommendations have encouraged the adoption of screening protocols among heart transplant units. However, there is still a lack of consensus about the correct course of action after dnDSA detection. Treatment is usually started when antibody-mediated rejection is present; however, some dnDSAs appear years before graft failure is detected, and at this point, damage may be irreversible. In particular, class II, anti-HLA-DQ, complement binding, and persistent dnDSAs have been associated with worse outcomes. Growing evidence points towards a more aggressive management of dnDSA. For that purpose, better diagnostic tools are needed in order to identify subclinical graft injury. Cardiac magnetic resonance, strain techniques, or coronary physiology parameters could provide valuable information to identify patients at risk. Treatment of dnDSA usually involves plasmapheresis, intravenous immunoglobulin, immunoadsorption, and ritxumab, but the benefit of these therapies is still controversial. Future efforts should focus on establishing effective treatment protocols in order to improve long-term survival of heart transplant recipients. Full article

(1) Background: The reconstruction of cutaneous defects following surgical procedures in the nasal pyramid presents a challenge due to the limited amount of available tissue. In cases of larger defects, skin from adjacent units is used. Traditionally, two-stage surgical flaps have been employed for reconstructing these defects. Tunnelized island flaps allow for the one-stage surgical reconstruction of nasal pyramid defects, using tissue from the forehead or cheek for the flap. (2) Methods: Descriptive retrospective study of 21 consecutive patients who underwent surgery for defects on the nasal pyramid using tunnelized island flaps. (3) Results: Surgical reconstruction was performed in 21 patients with basal cell carcinomas, 14 of them using the melolabial island flap and 7 using the paramedian forehead island flap. In all cases except one, clear histological margins were obtained. Immediate complications were mild and minor. It is worth noting the trapdoor effect complication, which improved over time in most cases, resulting in a satisfactory cosmetic outcome. No tumor recurrences were observed during an average follow-up period of 17.7 months. (4) Conclusions: Tunnelized island flaps allow for single-stage reconstruction of nasal pyramid defects, yielding excellent cosmetic results by utilizing adjacent skin. This procedure demands a certain level of skill but is associated with minimal complications, making it a valuable alternative in reconstructive dermatological surgery. Full article