Search Results (562)

Growing evidence indicates that altered melatonin secretion during critical illness may influence the quality and quantity of sleep, delirium, and overall recovery. However, limited data exist regarding the use of melatonin in pediatric critical illness. Data were reviewed over a 5-year period at a tertiary pediatric intensive care unit for pediatric patients (ages 0–18 years) who were prescribed melatonin with the aim of identifying the frequency of and indications for use. Data collection included the hospital day of initiation, the dose, the frequency, the duration of use, and the length of stay. The results demonstrate that melatonin was infrequently prescribed (6.0% of patients admitted; n = 182) and that the majority of patients received melatonin as continuation of home medication (46%; n = 83 of 182). This group had significantly earlier melatonin use (0.9 ± 2.3 day of hospitalization; p < 0.0001) and significantly reduced lengths of stay compared to the other groups (mean LOS 7.2 ± 9.3 days; p < 0.0001). Frequently, clear documentation of indication for melatonin use was absent (20%; n = 37). In conclusion, given that melatonin is infrequently used within a tertiary PICU with the most common indication as the continuation of home medication, and often without clear documentation for indication, this presents an opportunity to emphasize a more attentive and strategic approach regarding melatonin use in the PICU population. Full article

Background: Gastrointestinal stromal tumors (GISTs) are rare mesenchymal neoplasms of the gastrointestinal tract (GIT) that represent approximately 1 to 2 percent of primary gastrointestinal (GI) cancers. Owing to their rarity, very little is known about their overall epidemiology, and the prognostic factors of their pathology. The current study aimed to evaluate the independent determinants of mortality in patients diagnosed with GISTs over the past decade. Methods: Our study comprised 2374 patients diagnosed with GISTs from 2000 to 2017 from the Surveillance, Epidemiology, and End Results (SEER) database. We analyzed the baseline characteristics, and overall mortality (OM), as well as the cancer-specific mortality (CSM) of GISTs. Variables with a p value < 0.01 in the univariate Cox regression were incorporated into the multivariate Cox model, to determine the independent prognostic factors. Results: Multivariate Cox proportional hazard regression analyses of factors affecting the all-cause mortality and GIST-related mortality among US patients between 2010 and 2017 revealed a higher overall mortality in non-Hispanic Black patients (HR = 1.516, 95% CI 1.172–1.961, p = 0.002), patients aged 80+ (HR = 9.783, 95% CI 4.185–22.868, p = 0), followed by those aged 60–79 (HR = 3.408, 95% CI 1.488–7.807, p = 0.004); male patients (HR = 1.795, 95% CI 1.461–2.206, p < 0.001); patients with advanced disease with distant metastasis (HR = 3.865, 95% CI 2.977–5.019, p < 0.001), followed by cases with regional involvement via both direct extension and lymph node involvement (HR = 3.853, 95% CI 1.551–9.57, p = 0.004); and widowed patients (HR = 1.975, 95% CI 1.494–2.61, p < 0.001), followed by single patients (HR = 1.53, 95% CI 1.154–2.028, p = 0.003). The highest CSM was observed in the same groups, except widowed patients and patients aged 60–79. The highest CSM was also observed among patients that underwent chemotherapy (HR = 1.687, 95% CI 1.19–2.392, p = 0.003). Conclusion: In this updated study on the outcomes of patients with GISTs, we found that non-Hispanic Black patients, male patients, and patients older than 60 years have a higher mortality with GISTs. Furthermore, patients who have received chemotherapy have a higher GIST-specific mortality, and married patients have a lower mortality. However, we do not know to what extent these independent prognostic factors interact with each other to influence mortality. This study paves the way for future studies addressing these interactions. The results of this study may help treating clinicians to identify patient populations associated with a dismal prognosis, as those may require closer follow-up and more intensive therapy; furthermore, with married patients having a better survival rate, we hope to encourage clinicians to involve family members of the affected patients early in the disease course, as the social support might impact the prognosis. Full article

IBD consists of two diseases—CD and UC—that affect the digestive tract, with a greater affinity for the large bowel. In this case report, we focus on one of its most common complications. CDI is a pathology that is mostly secondary to UC. Another cause of this bacterial infection is established after the use of antibiotics, most commonly at the hospital level. Around 20 percent of CDI persists because of a chronic dysbiosis of the microbiota and low levels of antibodies against CD toxins. In this case report, we demonstrated mdCDI in a young woman after treatment with multiple drug therapies as well as with semi-invasive procedures as follows: antibiotics (vancomycin, fidaxomicin), anti-inflammatory agents (mesalamine, sulfasalazine), corticosteroids (budesonide, prednisone), integrin receptor antagonists (vedolizumab), several semi-invasive procedures such as fecal transplant microbiota (FMT), aminosalicylates (5-ASA), treatment with tumor necrosis factor (TNF) blockers (adalimumab, golimumab), and immunomodulators (upadcitinib, tofacitinib). This leads us to establish how rCDI and its resistance to different treatments make this a challenge for the health system, both for hospitals and for outpatients, as well as how time-consuming each treatment is from the first intake of the drug until its total efficacy or until patients reach a dose-response and time-response to the disease. Accordingly, this case report and other similar cases reflect the need for randomized control trials or meta-analyses to establish therapeutic guidelines for cases of mdCDI in the near future. Full article

Hereditary hemochromatosis (HH) is an autosomal recessive bleeding disorder characterized by tissue overload of iron. Clinical systemic manifestations in HH include liver disease, cardiomyopathy, skin pigmentation, diabetes mellitus, erectile dysfunction, hypothyroidism, and arthropathy. Arthropathy with joint pain is frequently reported at diagnosis and mainly involves the metacarpophalangeal and ankle joints, and more rarely, the hip and knee. Symptoms in ankle joints are in most cases non-specific, and they can range from pain and swelling of the ankle to deformities and joint destruction. Furthermore, the main radiological signs do not differ from those of primary osteoarthritis (OA). Limited data are available in the literature regarding treatment; surgery seems to be the gold standard for ankle arthropathy in HH. Pharmacological treatments used to maintain iron homeostasis can also be undertaken to prevent the arthropathy, but conclusive data are not yet available. This review aimed to assess the ankle arthropathy in the context of HH, including all its aspects: epidemiology, physiopathology, clinical and imaging presentation, and all the treatments available to the current state of knowledge. Full article

Type 2 diabetes mellitus (T2DM) is the world’s most common metabolic disease. The development of T2DM is mainly caused by a combination of two factors: the failure of insulin secretion by the pancreatic β-cells and the inability of insulin-sensitive tissues to respond to insulin (insulin resistance); therefore, the disease is indicated by a chronic increase in blood glucose. T2DM patients can be treated with mono- or combined therapy using oral antidiabetic drugs and insulin-replaced agents; however, the medication often leads to various discomforts, such as abdominal pain, diarrhea or constipation, nausea and vomiting, and hypersensitivity reactions. A biguanide drug, metformin, has been used as a first-line drug to reduce blood sugar levels. Sulfonylureas work by blocking the ATP-sensitive potassium channel, directly inducing the release of insulin from pancreatic β-cells and thus decreasing blood glucose concentrations. However, the risk of the failure of sulfonylurea as a monotherapy agent is greater than that of metformin or rosiglitazone (a thiazolidinedione drug). Sulfonylureas are used as the first-line drug of choice for DM patients who cannot tolerate metformin therapy. Other antidiabetic drugs, thiazolidinediones, work by activating the peroxisome proliferator-activated receptor gamma (PPARγ), decreasing the IR level, and increasing the response of β-cells towards the glucose level. However, thiazolidines may increase the risk of cardiovascular disease, weight gain, water retention, and edema. This review article aims to discuss case reports on the use of metformin, sulfonylureas, and thiazolidinediones in DM patients. The literature search was conducted on the PubMed database using the keywords ‘metformin OR sulfonylureas OR thiazolidinediones AND case reports’, filtered to ‘free full text’, ‘case reports’, and ‘10 years publication date’. In some patients, metformin may affect sleep quality and, in rare cases, leads to the occurrence of lactate acidosis; thus, patients taking this drug should be monitored for their kidney status, plasma pH, and plasma metformin level. Sulfonylureas and TZDs may cause a higher risk of hypoglycemia and weight gain or edema due to fluid retention. TZDs may be associated with risks of cardiovascular events in patients with concomitant T2DM and chronic obstructive pulmonary disease. Therefore, patients taking these drugs should be closely monitored for adverse effects. Full article

Venous thromboembolism (VTE), comprising pulmonary embolism (PE) and deep vein thrombosis (DVT), poses a significant risk during and after hospitalization, particularly for surgical patients. Among various patient groups, those undergoing major orthopedic surgeries are considered to have a higher susceptibility to PE and DVT. Major lower-extremity orthopedic procedures carry a higher risk of symptomatic VTE compared to most other surgeries, with an estimated incidence of ~4%. The greatest risk period occurs within the first 7–14 days following surgery. Major bleeding is also more prevalent in these surgeries compared to others, with rates estimated between 2% and 4%. For patients undergoing major lower-extremity orthopedic surgery who have a low bleeding risk, it is recommended to use pharmacological thromboprophylaxis with or without mechanical devices. The choice of the initial agent depends on the specific surgery and patient comorbidities. First-line options include low-molecular-weight heparins (LMWHs), direct oral anticoagulants, and aspirin. Second-line options consist of unfractionated heparin (UFH), fondaparinux, and warfarin. For most patients undergoing knee or hip arthroplasty, the initial agents recommended for the early perioperative period are LMWHs (enoxaparin or dalteparin) or direct oral anticoagulants (rivaroxaban or apixaban). In the case of hip fracture surgery, LMWH is recommended as the preferred agent for the entire duration of prophylaxis. However, emerging factor XI(a) inhibitors, as revealed by a recent meta-analysis, have shown a substantial decrease in the occurrence of VTE and bleeding events among patients undergoing major orthopedic surgery. This discovery poses a challenge to the existing paradigm of anticoagulant therapy in this specific patient population and indicates that factor XI(a) inhibitors hold great promise as a potential strategy to be taken into serious consideration. Full article

Background: Vestibulodynia (VBD) is the most common form of vulvodynia. Because VBD is a pain disorder, transcutaneous electrical nerve stimulation (TENS) can be used as treatment. This study aims to evaluate the effects of two-parameter combinations (frequency and pulse duration) of TENS in reducing pain intensity and dyspareunia in VBD. Methods: A randomized, double-blind, controlled trial was conducted to study the effect of two different electrical stimulation treatment regimens on women with VBD receiving domiciliary TENS. Outcomes were the mean change from baseline at 60 and 120 days of burning/pain and dyspareunia (VAS), Vulvar Pain Functional Questionnaire (V-Q), Female Sexual Functioning Index (FSFI) and vaginal electromyography measurements. Results: A total of 78 subjects, 39 in each group, completed the trial. Patients in Groups 1 and 2 received a mean of 46.9 and 48.4 TENS sessions. By day 120, there was a 38.2% reduction in the burning/pain and a 52.1% reduction in the dyspareunia VAS scores in Group 1, as compared to 21.3% (p = 0.003) and 23.1% in Group 2 (p = 0.01), respectively. FSFI, V-Q, and muscle-strength measures also improved but were not statistically significant. Conclusions: Our findings showed the potential of TENS in the treatment of VBD. Full article

Nephrotic syndrome (NS) is a common pediatric disease characterized by a dysfunction in the glomerular filtration barrier that leads to protein, fluid, and nutrient loss in urine. Corticosteroid therapy is the conventional treatment in children. Long-term complications of NS and prolonged exposure to steroids affect bones, growth, and the cardiovascular system. Diet can play an important role in preventing these complications, but there is a scarcity of scientific literature about nutritional recommendations for children with NS. They need individualized nutrition choices not only during the acute phase of the disease but also during remission to prevent the progression of kidney damage. The correct management of diet in these children requires a multidisciplinary approach that involves family pediatricians, pediatric nephrologists, dietitians, and parents. Full article

Von Hippel–Lindau (VHL) loss is the hallmark event characterizing the clear cell renal cancer subtype (ccRCC). Carriers of germinal VHL mutations have an increased prevalence of kidney cysts and ccRCC as well as hemangioblastoma, pheochromocytoma and pancreatic neuroendocrine tumors. In both sporadic and inherited ccRCC, the primary mechanism of VHL-mediated carcinogenesis is the abnormal stabilization of hypoxia-inducible factors (HIF1A and HIF2A). While HIF1A acts as a tumor suppressor and is frequently lost through inactivating mutations/14q chromosome deletions, HIF2A acts as an oncogene promoting the expression of its target genes (VEGF, PDGF, CAIX Oct4, among others). Selective HIF2a inhibitors block the heterodimerization between HIF2A and ARNT, stopping HIF2A-induced transcription. Several HIF2A inhibitors have entered clinical trials, where they have shown a favorable toxicity profile, characterized by anemia, fatigue and edema and promising activity in heavily pretreated ccRCC patients. Belzutifan, a second-generation HIF2a inhibitor, was the first to receive FDA approval for the treatment of unresectable ccRCC in VHL syndrome. In this review, we recapitulate the rationale for HIF2a blockade in ccRCC, summarize the development of HIF2a inhibitors from preclinical models up to its introduction to the clinic with emphasis on Belzutifan, and discuss their role in VHL disease management. Full article

Lateral elbow tendinopathy (LET) is a common upper limb pathology in people involved in manual occupations. The upper extremity functional index (UEFI) was specifically designed to evaluate functional limitations in patients with upper limb pathology. The UEFI was developed in English and has been translated into several languages, including Greek. However, it has been assessed only in patients with shoulder pathology. Thus, the aim of this study was to pilot-test the Greek version of the UEFI (GV-UEFI) questionnaire and assess its measurement properties in patients with LET. Thirty patients with LET were recruited and asked to fill in the GV-UEFI twice and the disabilities of arm, shoulder, and hand questionnaire (DASH) once. The internal consistency and test–retest reliability were examined using Cronbach’s alpha and the intraclass correlation coefficient (ICC). The standard error of measurement (SEM) and the minimum detectable change (MDC) were calculated and possible ground or ceiling effects were also examined. Convergent validity was evaluated with the Greek DASH using Pearson’s correlation. Lastly, the unidimensionality of the scale was examined through principal component analysis to verify construct validity. Internal consistency was high for the GV-UEFI (Cronbach’s a = 0.98) and test–retest reliability was excellent (ICC = 0.98). The SEM was 2.95 and the MDC was 6.85. Test–retest reliability of each item was good (ICC > 0.87). The correlation analysis demonstrated a strong correlation between the GV-UEFI and the DASH. No floor or ceiling effects were found. Principal component analysis verified the construct validity and the unidimensionality of the scale. The GV-UEFI was successfully tested in patients with LET. It seems that the GV-UEFI can be used reliably in Greek-speaking patients with LET. However, the measurement properties of this scale should be examined in a larger sample of LET patients. Full article

Combining omics data from different layers using integrative methods provides a better understanding of the biology of a complex disease such as cancer. The discovery of biomarkers related to cancer development or prognosis helps to find more effective treatment options. This study integrates multi-omics data of different cancer types with a network-based approach to explore common gene modules among different tumors by running community detection methods on the integrated network. The common modules were evaluated by several biological metrics adapted to cancer. Then, a new prognostic scoring method was developed by weighting mRNA expression, methylation, and mutation status of genes. The survival analysis pointed out statistically significant results for GNG11, CBX2, CDKN3, ARHGEF10, CLN8, SEC61G and PTDSS1 genes. The literature search reveals that the identified biomarkers are associated with the same or different types of cancers. Our method does not only identify known cancer-specific biomarker genes, but also proposes new potential biomarkers. Thus, this study provides a rationale for identifying new gene targets and expanding treatment options across cancer types. Full article

The present study evaluated the effectiveness and safety of corneal collagen cross-linking (CXL). A total of 886 eyes with progressive keratoconus were enrolled in a retrospective cohort study in a tertiary care university hospital. CXL was performed using a standard epithelium-off Dresden protocol. Visual outcomes, maximum keratometry (Kmax), demarcation line measurements, and complications were recorded. Visual outcomes and keratometric data were analyzed in a subgroup comprising 610 eyes. Uncorrected distance visual acuity (UDVA) improved from 0.49 ± 0.38 LogMAR to 0.47 ± 0.39 LogMAR (p = 0.03, n = 610) three years after the procedure, while corrected distance visual acuity (CDVA) improved from 0.15 ± 0.14 LogMAR to 0.14 ± 0.15 LogMAR (p = 0.007, n = 610). A significant reduction of Kmax from 56.28 ± 6.10 to 54.98 ± 6.19 (p < 0.001, n = 610) was observed three years after CXL. In five eyes (0.82%, 5/610) keratoconus progression continued after CXL. Three eyes were retreated successfully with documented refractive and topographic stability after five years. In the 35 eyes that completed 10 years of follow-up, mean visual acuity and topographic parameters remained stable. In conclusion, CXL is a safe and effective treatment for avoiding keratoconus progression. Long-term data are encouraging, supporting a high safety profile for this procedure. Full article

Head and neck squamous cell carcinoma (HNSCC) is a group of malignancies, involving the oral cavity, pharynx, hypopharynx, larynx, nasal cavity, and salivary glands, that together compose the seventh most common cancer diagnosis worldwide. With 890,000 new cases and 450,000 deaths annually per GLOBOCAN estimates, HNSCC accounts for roughly 4.5% of cancer diagnoses and deaths. In the developing world, the incidence of HNSCC is growing with increasing consumption of tobacco (smoked or chewed), alcohol, and areca nut (betel quid). Alcohol and tobacco have a synergistic effect, with the heavy consumption of both increasing HNSCC risk 40-fold. In developed nations, HPV-related HNSCC surpasses tobacco- and alcohol-related disease. HPV-related HNSCC more commonly affects the oropharynx, hypopharynx, and larynx than the oral cavity, and is associated with a significantly longer median survival (130 months vs. 20 months). Discrepancies in etiology as well as disparities in lifestyle choices and access to healthcare may account for the greater incidence and poorer survival of HNSCC among minority and lower-socioeconomic-status communities in developed nations. Pharmacotherapy and counseling together have been shown to be effective in promoting smoking and alcohol cessation. Education on cancer risk and community engagement have reduced areca nut consumption in Asia as well as in diaspora communities. HPV vaccination, starting at age 11–12 for both sexes, has been shown to reduce the prevalence of high-risk HPV serologies and prevent pre-cancerous lesions of the cervix, vagina, and vulva. As of 2020, 58.6% of eligible adolescents in the US have received the full two-vaccine series. Increased adoption of vaccination, education on safe sex practices, and routine visual oral screening for high-risk patients would curb growing HNSCC incidence in developed nations. Full article

Hypoxia is characterized as one of the main consequences of sepsis, which is recognized as the leading cause of death in intensive care unit (ICU) patients. In this study, we aimed to examine whether the expression levels of genes regulated under hypoxia could be utilized as novel biomarkers for sepsis prognosis in ICU patients. Whole blood expression levels of hypoxia-inducible factor-1α (HIF1A), interferon-stimulated gene 15 (ISG15), hexokinase 2 (HK2), lactate dehydrogenase (LDHA), heme oxygenase-1 (HMOX1), erythropoietin (EPO), and the vascular endothelial growth factor A (VEGFA) were measured on ICU admission in 46 critically ill, initially non-septic patients. The patients were subsequently divided into two groups, based on the development of sepsis and septic shock (n = 25) or lack thereof (n = 21). HMOX1 mRNA expression was increased in patients who developed sepsis/septic shock compared to the non-septic group (p < 0.0001). The ROC curve, multivariate logistic regression, and Kaplan–Meier analysis demonstrated that HMOX1 expression could be utilized for sepsis and septic shock development probability. Overall, our results indicate that HMOX1 mRNA levels have the potential to be a valuable predictive factor for the prognosis of sepsis and septic shock in ICU patients. Full article