Quality of Life in Patients with Phenylketonuria: A Systematic Review.

The impact of phenylketonuria (PKU) on Quality of life (QoL) has been a topic of interest in recent research. This article reviews current researches on the impact of PKU on QoL. The review examines factors that may influence QoL, such as age, metabolic control, and treatment adherence. In this systematic review study, relevant articles were identified using a search strategy built with the keywords phenylketonuria, PKU, or hyperphenylalaninemia (or their synonyms) and QoL in Web of Science, Scopus, and PubMed databases. After identifying the articles, duplicates, reviews, scientific abstracts, articles published in languages other than English, and non relevant studies were excluded. The search strategy identified 951 records from databases, and after excluding duplicates, irrelevant studies, and those published in non English languages, 26 records were left that contained data on 1816 patients with PKU/hyperphenylalaninemia. The studies included both children/adolescents and adults. Overall, the studies found that the QoL of PKU patients was comparable to normative data, but some aspects such as emotional health and school functioning were lower. Metabolic control was found to significantly correlate with QoL. Younger patients and men had better QoL in several studies, while late treated patients and those with lower education had worse outcomes. It is concluded that QOL in patients with PKU is similar to the general population. However, given the chronic nature of the condition, it is important to pay special attention to their QoL. Poor QOL is associated with female gender, lower education, older age, and poor metabolic control.

Final height in children and adolescents with type 1 diabetes mellitus: A systematic review and meta-analysis.

PURPOSE: Considering the high prevalence of type 1 diabetes mellitus (T1DM) together with the importance of improved physical growth and the significance of promoting healthcare quality among T1DM children, this meta-analysis aims to determine mean final height in this population group. METHODS: We systematically searched PubMed, EMBASE, Web of Science, Scopus, and Cochrane databases for all studies published until May 2023 and reviewed references of published articles. Meta-analytic procedures were used to estimate the effect size (mean final height Z-score) among T1DM children in a random effects model. Significance values, weighted effect sizes, 95% CIs, and tests of homogeneity of variance were calculated. The included studies consisted of data from 3274 patients. RESULTS: The mean final height Z-score for T1DM children was -0.201 (n = 25 studies, 95% CI: -0.389, -0.013; I2 = 97%), -0.262 in males (n = 20 studies, 95% CI: -0.539, 0.015, I2 = 97.1%), and -0.218 in females (n = 18 studies, 95% CI: -0.436, 0, I2 = 94.2%). The non-significant negative association between age at diagnosis, HbA1c levels, and final height Z-score is suggested by the findings of the univariate meta-regression. CONCLUSION: Our findings indicated that children with T1DM have impaired linear growth and that monitoring of growth in these patient populations is an important issue in the management of T1DM. Due to a scarcity of studies providing data on the relationship between uncontrolled diabetes (increased HbA1c) and early diagnosis and final height, further investigation is warranted to determine whether there is indeed a correlation. Consequently, any conclusion regarding the association between uncontrolled diabetes (elevated HbA1c), early diagnosis of T1DM, and the increased risk of impaired linear growth or final height remains uncertain.

Masitinib: The promising actor in the next season of the Amyotrophic Lateral Sclerosis treatment series.

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease with high mortality and morbidity rate affecting both upper and lower motor neurons (MN). Muscle force reduction, behavioral change, pseudobulbar affect, and cognitive impairments are the most common clinical manifestations of ALS. The main physiopathology of ALS is still unclear, though several studies have identified that oxidative stress, proteinopathies, glutamate-related excitotoxicity, microglial activation, and neuroinflammation may be involved in the pathogenesis of ALS. From 1995 until October 2022, only Riluzole, Dextromethorphan Hydrobromide (DH) with Quinidine sulfate (Q), Edaravone, and Sodium phenylbutyrate with Taurursodiol (PB/TUDCO) have achieved FDA approval for ALS treatment. Despite the use of these four approved agents, the survival rate and quality of life of ALS patients are still low. Thus, finding novel treatments for ALS patients is an urgent requirement. Masitinib, a tyrosine kinase inhibitor, emphasizes the neuro-inflammatory activity of ALS by targeting macrophages, mast cells, and microglia cells. Masitinib downregulates the proinflammatory cytokines, indirectly reduces inflammation, and induces neuroprotection. Also, it was effective in phase 2/3 and 3 clinical trials (CTs) by increasing overall survival and delaying motor, bulbar, and respiratory function deterioration. This review describes the pathophysiology of ALS, focusing on Masitinib's mechanism of action and explaining why Masitinib could be a promising actor in the treatment of ALS patients. In addition, Masitinib CTs and other competitor drugs in phase 3 CTs have been discussed.

Fistulectomy and primary sphincteroplasty in complex anal fistula treatment: a hospital-based long-term follow-up study.

BACKGROUND: Currently, there is no agreement on the best treatment for complex anal fistulas with the least recurrence and lowest complication rate. The aim of this study was to evaluate the long-term recurrence and incontinence after fistulectomy and primary sphincteroplasty (FIPS) in a group of patients with complex perianal fistula. METHODS: This prospective observational study was done at the colorectal ward of Taleghani Hospital of Tehran from January 2010 to December 2020. Patients with anal fistula who underwent FIPS were studied. After surgery, patients were evaluated regularly by a colorectal surgeon for fistula recurrence and incontinence. Recurrence was described as a new fistula tract formation after the initial cure and failure of healing in the operation site or any purulent discharge from the fistula tract and openings. In addition, the patient's continence was assessed based on the Wexner score. RESULTS: There were 335 patients (66 men and 269 women, mean age 42.74 ± 12.44 years), 191 of them with low fistula and 144 with high fistula. Thirteen patients (3.90%) experienced recurrence (all had a low fistula). Thirty-nine patients (11.64%), 19 patients with high and 20 patients with low fistula, had a Wexner score ≥ 3 during the follow-up. Fifteen patients were lost to follow-up. Male patients (OR = 2.67, 95% CI 0.84, 8.45, p = 0.094, adjusted OR = 4.41, 95% CI 1.05, 18.48, p = 0.042), patients with low fistula (p = 0.001), and recurrent cases had a significantly higher rate of recurrence (OR = 10.38, 95% CI 3.24-33.20 p ≤ 0.001, adjusted OR = 23.36, 95% CI 4.35-125.39, p ≤ 0.001). A significant correlation between body mass index > 35 kg/m2 and incontinence was found (OR = 4.40, 95% CI 1.35, 14.33, p = 0.014). CONCLUSIONS: In the present study, an acceptable healing rate and a low percentage of complications following FIPS were seen in patients with complex anal fistula. Randomized clinical trials with appropriate follow-up duration and sample size comparing different surgical methods in these patients are needed to confirm these results.

Hepatic Disorders and COVID-19: From Pathophysiology to Treatment Strategy.

Following the SARS-CoV-2 outbreak and the subsequent development of the COVID-19 pandemic, organs such as the lungs, kidneys, liver, heart, and brain have been identified as priority organs. Liver diseases are considered a risk factor for high mortality from the COVID-19 pandemic. Besides, liver damage has been demonstrated in a substantial proportion of patients with COVID-19, especially those with severe clinical symptoms. Furthermore, antiviral medications, immunosuppressive drugs after liver transplantation, pre-existing hepatic diseases, and chronic liver diseases such as cirrhosis have also been implicated in SARS-CoV-2-induced liver injury. As a result, some precautions have been taken to prevent, monitor the virus, and avoid immunocompromised and susceptible individuals, such as liver and kidney transplant recipients, from being infected with SARS-CoV-2, thereby avoiding an increase in mortality. The purpose of this review was to examine the impairment caused by SARS-CoV-2 infection and the impact of drugs used during the pandemic on the mortality range and therefore the possibility of preventive measures in patients with liver disease.

Carotid Body Tumor: Our Experience with 42 Patients and a Literature Review.

To review characteristics, signs, diagnostic methods, and surgical complications in patients with carotid body tumor, in addition to a literature review. This was a cross-sectional study carried out on 42 patients with carotid body tumors referred to Al-Zahra hospital of Isfahan from January 1, 2016, to December 31, 2019. The studied characteristics included age at the onset of symptoms, gender, symptoms, duration of symptomatic status before diagnosis, diagnostic methods, pathological outcome, tumor stage, and surgical complications. The collected data were analyzed using SPSS 21. In this study, 34 patients (80.96%) were female. The mean age at the onset of symptoms was 54.41 years. The mean duration of symptoms before diagnosis was 12.55 months. There was no significant difference between genders for the age and duration of symptoms before diagnosis (p > 0.05). Symptoms were mainly painless mass, hoarseness, coughing, earache, tinnitus, and headache. After surgery, two cases of permanent cranial nerve injuries were found. Thirty-nine patients (93%) were diagnosed by ultrasound imaging and CT scan. We had one case of arterial repair. There was one malignant and one functional tumor. According to the results, carotid body tumor is more common in females especially on the right side. Bilateral tumors are prevalent in females. This mass should be removed by surgery at the time of diagnosis in cases where the patient is not at high risk for surgery due to comorbidities, and the risk of complications following surgery is low. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-021-02453-8.

Severe acute respiratory syndrome coronavirus 2 infection: Role of interleukin-6 and the inflammatory cascade.

Since December 2019, a novel coronavirus that represents a serious threat to human lives has emerged. There is still no definite treatment for severe cases of the disease caused by this virus, named coronavirus disease 2019 (COVID-19). One of the most considered treatment strategies targets the exaggerated immune regulator, and interleukin (IL)-6 is a crucial pro-inflammatory mediator. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases show an elevated level of IL-6 related to disease severity. IL-6 activity can be inhibited by the following: IL-6 itself, IL-6 signaling pathways such as Janus kinase and signal transducer and activator of transcription (JAK-STAT), gp130, IL-6R, and downstream activated ILs, such as IL-17 and IL-6 cytokine. Currently, according to these studies and their results, IL-6 blockade with anti-IL-6 or its receptor antibodies such as tocilizumab in COVID-19 is beneficial in severe cases and may reduce the mortality rate. JAK-STAT inhibitors block the cytokine storm by inhibiting several crucial pro-inflammatory mediators such as TNF-α and IL-6 and have shown various results in clinical trials. IL-6 induces IL-17 secretion, and IL-17 is involved in the pathogenesis of inflammatory processes. Clinical trials of anti-IL-17 drugs are currently recruiting, and anti-gp130 antibody is preclinical. However, this agent has shown positive effects in inflammatory bowel disease clinical trials and could be tested for SARS-CoV-2. This study aimed to review the role of IL-6 in the cytokine storm and studies regarding IL-6 and blockade of its inflammatory pathways in COVID-19 to determine if any of these agents are beneficial for COVID-19 patients.

Cognitive function in untreated subjects with mild hyperphenylalaninemia: a systematic review.

BACKGROUND: This systematic review study aims to evaluate the cognitive function of patients with mild hyperphenylalaninemia (mHPA) without treatment. METHODS: A systematic literature search was done from the 1st of May to the 30th of July in 2021 on published studies. The search strategy was ((hyperphenylalaninemia) OR (phenylketonuria) AND (cognition)). We use PubMed, Scopus, and the Web of Science databases. Studies which reported their findings regarding the cognitive function of patients with mHPA (screening serum phenylalanine > 120 and < 600 µmol/L) were included and reviewed. RESULTS: From initially retrieved 2805 studies, finally, 15 studies (10 on untreated patients with Phe levels below 360 µmol/L, 7 on untreated patients with Phe levels between 360 and 600 µmol/L, four 120-600 µmol/L) were selected. Most of the studies used the Wechsler Intelligence Scale for IQ evaluation, two (2/15) of them used the Stanford-Binet test and two used both tests. Four studies have reported a worse cognitive outcome compared to the control group, and in one study, relative defects in attention and working memory were reported. Other studies have reported normal IQ levels and no significant cognitive defects. CONCLUSION: It is suggested that Phe levels between 120 and 360 µmol/L are generally safe. Some studies showed that untreated patients with higher levels might show some degrees of cognitive impairment. In conclusion, current knowledge is insufficient to state that treatment is not required for HPA patients to preserve their cognitive status, especially in patients with Phe levels of 360-600 µmol/L. Further studies with a larger sample size and standardized cognitive function evaluation tools are needed.

New-onset acute ischemic stroke following COVID-19: A case-control study.

Background: Neurological manifestations of coronavirus disease 2019 (COVID-19) have been highlighted. COVID-19 potentially increases the risk of thromboembolism. We aimed to compare patients with COVID-19 with and without new-onset acute ischemic stroke (AIS). Materials and Methods: In this single-center retrospective case-control study, demographics, clinical characteristics, laboratory findings, and clinical outcomes were compared between 51 patients with both COVID-19 and AIS (group A) and 160 patients with COVID-19 and without AIS (group B). Results: Patients in group A were significantly older, more likely to present with critical COVID-19 (P = 0.004), had higher rates of admission in the intensive care unit (P < 0.001), more duration of hospitalization (P < 0.001), and higher in-hospital mortality (P < 0.001). At the time of hospitalization, O2 saturation (P = 0.011), PH (P = 0.04), and HCO3 (P = 0.005) were lower in group A. White blood cell count (P = 0.002), neutrophil count (P < 0.001), neutrophil-lymphocyte ratio (P = 0.001), D-Dimer (P < 0.001), blood urea nitrogen (BUN) (P < 0.001), and BUN/Cr ratio (P < 0.001) were significantly higher in patients with AIS. Conclusion: Stroke in COVID-19 is multifactorial. In addition to conventional risk factors of ischemic stroke (age and cardiovascular risk factors), we found that patients with more severe COVID-19 are more prone to ischemic stroke. Furthermore, leukocyte count, neutrophil count, neutrophil-lymphocyte ratio, D-Dimer, BUN, and BUN/Cr ratio were higher in patients with AIS following COVID-19 infection.