Recognizable Cause Research Articles

CATALOG OF LANDSLIDES OF THE CITY OF ZENICE WITH SPECIFIC CAUSES

As part of its activities, the Federal Institute of Geology carries out mapping of active landslides in the territory of the Federation of Bosnia and Herzegovina, and my task is to map instability in the area of the City of Zenica. A very large number of landslides were registered during the catastrophic rainfall that occurred in 2014. Following these phenomena and certain records, detailed mapping of unstable slopes and records of unstable surfaces was started. The cadastre is defined in such a way that it displays all input data with location polygons in GIS. Not in the field, quite recognizable causes were observed, which are always a combination of bad geological and hydrogeological conditions with a significant anthropogenic factor. The slope of the terrain is also very unfavourable, and gravity also played a significant role in the instability of these slopes. Almost all registered landslides have unregulated water (surface, underground, waste). The frequent occurrence of earthquakes on this section also significantly threatened the stability of slopes and buildings, and on the spot, the consequences of cracking and shearing of buildings were evident as a result of the earthquake. A special review will be given to the activation of mudflows during extensive rainfall in this area, which is not rare. A significant share in the formation of mudflows belongs to heavy precipitation, which over time formed the so-called "watersheds" where water was transported from higher to lower parts of the slope. However, during the climate changes, there was a significant increase in the amount and frequency of precipitation, which carried the surface cover and rock blocks that were moved down the steep slopes. Road approaches to the villages, as well as a significant number of buildings, made artificial dams and cut cuts that were a natural way of draining water. So you have a significant number of buildings built exactly on these "watersheds" that represent the dam. In the newly created situation, by changing the natural paths of movement of surface and underground water, it would be necessary to regulate the water below and around the road strip, as well as the drainage of water around buildings. Only after the water has been drained, certain geotechnical procedures can be carried out to stabilize the slope and to permanently rehabilitate it, so that the inhabitants of these villages do not constantly fear during rainfall.

Imaging Review of Pediatric Monogenic CNS Vasculopathy with Genetic Correlation.

Monogenic cerebral vasculopathy is a rare but progressively recognizable cause of pediatric cerebral vasculopathy manifesting as early as fetal life. These monogenic cerebral vasculopathies can be silent or manifest variably as fetal or neonatal distress, neurologic deficit, developmental delay, cerebral palsy, seizures, or stroke. The radiologic findings can be nonspecific, but the presence of disease-specific cerebral and extracerebral imaging features can point to a diagnosis and guide genetic testing, allowing targeted treatment. The authors review the existing literature describing the frequently encountered and rare monogenic cerebral vascular disorders affecting young patients and describe the relevant pathogenesis, with an attempt to categorize them based on the defective step in vascular homeostasis and/or signaling pathways and characteristic cerebrovascular imaging findings. The authors also highlight the role of imaging and a dedicated imaging protocol in identification of distinct cerebral and extracerebral findings crucial in the diagnostic algorithm and selection of genetic testing. Early and precise recognition of these entities allows timely intervention, preventing or delaying complications and thereby improving quality of life. It is also imperative to identify the specific pathogenic variant and pattern of inheritance for satisfactory genetic counseling and care of at-risk family members. Last, the authors present an image-based approach to these young-onset monogenic cerebral vasculopathies that is guided by the size and predominant radiologic characteristics of the affected vessel with reasonable overlap. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

Treating the untreatable: Somatoform disorder in an adolescent with organic symptoms mimicking idiopathic anaphylaxis

Idiopathic anaphylaxis (IA) is a rare life-threatening disorder that may present with severe symptoms similar to other forms of anaphylaxis. It is an exclusion diagnosis and requires careful consideration of all recognizable and rare causes of anaphylaxis. Psychiatric conditions, such as somatoform disorders, should be considered in the differential diagnosis when there is a paucity or absence of clinical signs. A 17-year-old female patient was admitted to the inpatient clinic for pediatric allergy due to recurrent anaphylaxis. In the last two years, the patient was administered intramuscular epinephrine more than 200 times and was admitted to the intensive care unit four times due to severe anaphylaxis. The attacks frequently appeared as flushing, itching, shortness of breath, and rarely hypotension, but without a defined trigger. The patient was diagnosed with IA and received oral steroids, omalizumab, and rituximab. However, none of her attacks were accompanied by elevated tryptase levels and the aforementioned pharmacotherapies did not prevent relapse. After psychiatric evaluation, somatoform disorders were suspected despite striking variations in the severity of the physical symptoms. The psychiatric diagnosis was also supported by a good response to fluoxetine and supportive individual psychotherapy. The patient is currently being followed up without any anaphylactic attacks. Somatoform disorders should be considered in the differential diagnosis of IA because of overlapping physical symptoms. In the clinical practice of diagnosing and managing IA, symptoms that are not only subjective but also objective and unresponsive to conventional treatments should alert physicians to the probability of the psychiatric condition and the requirement for psychiatric consultation.

Defining the "Cutoff" on the Urethral Caliber in Diagnosing a Female Urethral Stricture.

Introduction The rarity in detecting female urethral stricture (FUS) backed by the inconsistency regarding the cutoff on the caliber to direct any treatment for its increase poses a challenge to its existence. Therefore, the present study was conducted to determine the caliber of the urethra that clearly identifies aFUS. Materials and method In this prospective observational study conducted between November 2015 and July 2017, women with obstructive lower urinary tract symptoms (LUTS) and a history of relief on at least a single urethral dilatation were included if the American Urological Association (AUA) score was more than seven and the maximum flow rate (Qmax) was less than 20 mL/sec. Of the 71 women recruited, 10 women had recognizable external causes: caruncle (five), mucosal prolapse (three), and meatal stenosis (two). The remaining 61 underwent voiding cystourethrogram (VCUG) and urodynamics followed by urethrocystoscopy, if the findings suggested a stricture. A definitive diagnosis was sought in those without stricture disease. We categorized all patients as either having a "true" stricture or an alternate etiology. Categorical variables were presented in number and percentage (%) and continuous variables as mean ± standard deviation (SD). Results The mean dilatationranged between one and six; the mean AUA score, ~17.82 ± 3.59; mean Qmax, ~10.21 ± 3.39 mL/sec; and the mean post-void residue (PVR), 106.65 ± 51 mL. A total of 29 patients were diagnosed to have stricture (dense = 17; flimsy = 12). None of the patients in this group had a urethral caliber of more than 14 French (Fr). Other etiologies were dysfunctional voiding (17), underactive bladder (seven), cystocele (four), and primary bladder neck obstruction (PBNO) (four). Conclusion Women with voiding LUTS should be screened for FUS only if the urethral caliber is ≤14 Fr.

Senile Pruritis (SP) - An Emerging Geriatric Public Health Problem (EGPHP)!

Background: Itching in any part of the body without a primary rash and in the absence of xerosis or other recognizable causes in a person over 65 years old is called Senile Pruritis. Though Pruritus is a relatively common symptom everybody experiences at any point in their life, it impacts quality of life among elderly population. Materials and Methods: This article is based on managing 2 cases and another rare case managed by the Dermatology department of a government medical college that was taken for medico-social case study for MPH scholars in the last 2 years. Relevant literature search on etiology and management practices across the globe complimented the article. Results: While the rare case taught the MPH scholars i) Idiopathic generalized pruritus is a diagnosis of exclusion, that is often difficult for primary health care providers to treat, ii) with Patients with uncontrolled idiopathic pruritus, failing to respond to standard treatment of topical applications, antihistamines and cortisone, Low-dose gabapentin can be tried. iii) An empathetic support from the family contributes to medical management. Two other cases are just a few days old, but responding to standard treatment well, need to be followed up for final long-term outcome. The standard approach consists of i) Oral antihistamines (containing Fexofenadine) ii) Chlorpromazine 25 mg at night for addressing Psychogenic component and iii) Topical application of Crotamiton 10% lotion on affected skin surface twice a day after bath.

Warburg-Effect Driven Lactic Acidosis Is Associated with Early Death in Patients with Lymphoma

Introduction: Lactic acidosis is a medical emergency and in most cases results from an imbalance between tissue oxygenation and oxygen demand (Type A). However, Type B lactic acidosis occurs in the absence of a recognizable impairment in systemic oxygen delivery, and is most commonly associated with drug or toxin ingestion, sepsis, severe nutritional deficits such as thiamine, and less commonly, malignancy. The capacity of shifting glucose metabolism to anaerobic pathway despite the presence of adequate oxygen, enhancing the rate of glucose uptake, accelerated glycolysis and hence producing more lactate, is a well-defined phenomenon in malignant cell metabolism, and is called the Warburg Effect (WE) or aerobic glycolysis. A systemic rise in lactate and lactic acidosis has been reported in hematologic malignancies and less commonly in solid tumors, and is thought to occur as a consequence of both increased production of lactate- reflecting high malignancy burden, and impaired lactate turnover or elimination by liver or kidney. Few case reports or series have demonstrated a possible correlation between early death and elevated lactate in patients with hematologic malignancy (Table 1). We aimed to characterize the incidence and clinical impact of Warburg-driven lactic acidosis on outcome including early death. Methods: A retrospective study of patients admitted to the haemato-oncology department in a large tertiary medical center between the years 2013- 2022, that presented with elevated lactate levels during the first week of admission. Patients with hematologic diseases other than lymphoma were excluded. Of 40 patients reviewed, 21 patients were excluded because of underlying hematological malignancy other than lymphoma. Medical records were retrieved and reviewed for a recognizable cause for elevated lactate, or non (assigned as the WE group). Early-death was defined as death of any cause within 4 weeks of admission. Results: Nineteen patients had lymphoma and elevated lactate levels within the first week of admission. Of these, 12 patients fulfilled the criteria for WE and 7 patients had their high lactate attributed to other causes such as hemorrhagic shock (n=1), sepsis (n=5) and concomitant metformin use (n=1). Median age among patients with WE was 72.5 years (range 66-86) with 41.6% (n=5) males. All but one had aggressive lymphoma. Diffuse Large B cell Lymphoma was the most frequent type (n=9) followed by T cell Lymphoma (n=2) and follicular lymphoma (n=1). Most patients had advanced disease (Stage III-IV in 75%) and the median International Prognostic Index (IPI) of the patients was 4 (range 3-5). The median lactate level was 31.5 mg/dL (range 25-64; with upper limit of normal value-20 mg/dL). Two patients received thiamin therapy once WE was recognized. Early-death rate was 75% (9 patients) among patients with WE. The established cause of death in this population was: sepsis (n=3), DIC (n=1), uremia and multi organ failure (n=2) and respiratory failure due to lung infiltration by lymphoma (n=3). Both steroid and chemotherapy were initiated earlier in surviving patients as compared to those who died early (within 4 weeks of admission); in surviving patients, chemotherapy was initiated at a median of 3 days before first elevated lactate was detected (range (-)7-1), and steroids at median of 3 days before first elevated lactate was detected, while in those who died early, chemotherapy was initiated at median of 5 days after first elevated lactate was detected (range (-)2-18) and steroids at median 1 day after first elevated lactate (p=0.29 and 0.05 for steroids and chemo, respectively). (Table 2). Conclusion: Warburg driven lactic acidosis is a marker of ‘acute cancer’ in lymphoma patients and is associated with a very high mortality rate. Early recognition of this very high-risk clinical scenario is of utmost importance and should prompt immediate anti-lymphoma therapy that may improve outcome.

Chronic Kidney Disease of Unknown Etiology: A Single-center Cross-sectional Study.

Globally, chronic kidney disease of unknown etiology (CKDu) has been recognized as an emerging cause contributing to the rise in chronic kidney disease (CKD). Nevertheless, in the Kingdom of Saudi Arabia, the epidemiology of CKDu remains understudied. The aim of this study was to assess the epidemiological, clinical, and laboratory characteristics of the CKDu population. From May 2021 to May 2022, a retrospective cross-sectional study was conducted on patients with Stage 4-5 CKD who presented to King Fahd Hospital in Jeddah. On the basis of the cause of CKD, patients were categorized into two groups: those with traditional risk factors for CKD (CKDt) and those without a recognizable cause of CKD (CKDu). Out of a total of 500 patients with Stage 4-5 CKD who were enrolled in the study, 100 patients were found to have CKDu. Compared with the 400 patients with CKDt, the patients in the CKDu group were younger (a mean age of 52.3 years vs. 66.1 years, P <0.001), with the majority in the middle age group of 40-65 years old (68% vs. 43%, P <0.001). They were predominantly males (72% vs. 56%, P = 0.003), with less hyperkalemia (4.29 vs. 5.13, P <0.043), and presented without a previous history of CKD (57% vs. 31%, P = 0.001). Among the 500 patients who were studied, 100 patients (20%) presented with CKDu who were predominantly younger males without a known history of CKD. Further studies on a nationwide scale are warranted.

Diagnostic Value of Ascitic Endocan Levels in the Diagnosis of the Spontaneous Bacterial Peritonitis

Abstract Background Spontaneous bacterial peritonitis (SBP) is a serious complication of liver cirrhosis and is defined as infected ascites in the absence of any recognizable secondary cause of infection. One of the possible mechanisms of developing Spontaneous bacterial peritonitis is bacterial translocation. Aim of the Work The aim of this study is to assess the role of ascitic endocan levels in the diagnosis of SBP in decompensated cirrhosis. Patients and Methods 90 cirrhotic patients with ascites were included in the current study and divided into 2 groups: SBP group with positive ascites culture or with an AF PMNL count ≥ 250/mm3 included 45 subjects. Non SBP group with negative ascites culture or with an AF PMNL count &amp;gt; 250/mm3 included 45 subjects. In the SBP group, the mean age was 58.77 years with male predominance (68.8%).As regard to Non SBP group, the mean age was 59.31 years with male predominance 57.8%. Results There was a statistical significant difference in between SBP group and Non-SBP group as regard to Platelets, ALT, ascetic Total leucocyte count, Protein and LDH. The most common presentation in SBP group was Upper GIT bleeding and Abdominal pain and the most common organism detected in the culture of ascitic fluid Escherichia coli (80%) followed by Streptococcus viridans (15.5%). Ascitic Endocan level was significantly higher in SBP group than Non-SBP group with P &amp;lt; 0.001. The sensitivity and specificity of Ascitic Endocan in detection of SBP were 84.85% and 82.69% respectively. There was a positive significant correlation in between Ascitic Endocan level and ALT, AST, bilirubin, CRP, Child class, MELD score, Blood Leukocytes and TLC (cell/mm3) in ascitic fluid in SBP group. The significant predictors of bad outcome in patients with SBP were higher ascitic fluid Endocan level, CRP and higher Glucose in ascitic fluid (mg/dl) levels Conclusion High Ascitic endocan level is common in cirrhotic patients with SBP than in Non-SBP and that means Ascitic endocan is related to the severity of the disease. Ascitic endocan level is an independent risk factor for SBP. High Ascitic endocan level is a significant predictor of bad outcome in patients with SBP. Therefore, measurement of Ascitic endocan level provide a new strategy to more aggressive treatments for high-risk groups. Ascitic endocan level could be used as an inflammatory biomarker for the prognosis of patients with SBP

Maleic acid is a biomarker for maleylacetoacetate isomerase deficiency; implications for newborn screening of tyrosinemia type 1.

Dried blood spot succinylacetone (SA) is often used as a biomarker for newborn screening (NBS) for tyrosinemia type 1 (TT1). However, false-positive SA results are often observed. Elevated SA may also be due to maleylacetoacetate isomerase deficiency (MAAI-D), which appears to be clinically insignificant. This study investigated whether urine organic acid (uOA) and quantitative urine maleic acid (Q-uMA) analyses can distinguish between TT1 and MAAI-D. We reevaluated/measured uOA (GC-MS) and/or Q-uMA (LC-MS/MS) in available urine samples of nine referred newborns (2 TT1, 7 false-positive), eight genetically confirmed MAAI-D children, and 66 controls. Maleic acid was elevated in uOA of 5/7 false-positive newborns and in the three available samples of confirmed MAAI-D children, but not in TT1 patients. Q-uMA ranged from not detectable to 1.16 mmol/mol creatinine in controls (n = 66) and from 0.95 to 192.06 mmol/mol creatinine in false-positive newborns and MAAI-D children (n = 10). MAAI-D was genetically confirmed in 4/7 false-positive newborns, all with elevated Q-uMA, and rejected in the two newborns with normal Q-uMA. No sample was available for genetic analysis of the last false-positive infant with elevated Q-uMA. Our study shows that MAAI-D is a recognizable cause of false-positive TT1 NBS results. Elevated urine maleic acid excretion seems highly effective in discriminating MAAI-D from TT1.

A Higher Abundance of Actinomyces spp. in the Gut Is Associated with Spontaneous Preterm Birth.

Preterm birth is a major challenge in pregnancy worldwide. Prematurity is the leading cause of death in infants and may result in severe complications. Nearly half of preterm births are spontaneous, but do not have recognizable causes. This study investigated whether the maternal gut microbiome and associated functional pathways might play a key role in spontaneous preterm birth (sPTB). Two hundred eleven women carrying singleton pregnancies were enrolled in this mother-child cohort study. Fecal samples were freshly collected at 24-28 weeks of gestation before delivery, and the 16S ribosomal RNA gene was sequenced. Microbial diversity and composition, core microbiome, and associated functional pathways were then statistically analyzed. Demographic characteristics were collected using records from the Medical Birth Registry and questionnaires. The result showed that the gut microbiome of mothers with over-weight (BMI ≥ 24) before pregnancy have lower alpha diversity than those with normal BMI before pregnancy. A higher abundance of Actinomyces spp. was filtered out from the Linear discriminant analysis (LDA) effect size (LEfSe), Spearman correlation, and random forest model, and was inversely correlated with gestational age in sPTB. The multivariate regression model showed that the odds ratio of premature delivery was 3.274 [95% confidence interval (CI): 1.349; p = 0.010] in the group with over-weight before pregnancy with a cutoff Hit% > 0.022 for Actinomyces spp. The enrichment of Actinomyces spp. was negatively correlated with glycan biosynthesis and metabolism in sPTB by prediction from the Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) platform. Maternal gut microbiota showing a lower alpha diversity, increased abundance of Actinomyces spp., and dysregulated glycan metabolism may be associated with sPTB risk.

A STUDY OF PREVALENCE, FREQUENCY AND RISK FACTORS OF NONALCOHOLIC FATTY LIVER DISEASE IN TYPE 2 DIABETES PATIENTS.

Introduction: In the absence of other clearly recognisable causes of fat accumulation, non-alcoholic fatty liver disease is a chronic liver disorder characterised by insulin resistance and hepatic fat build up. NAFLD patients are more likely to have diabetes, dyslipidemia, hypertension, and cardiovascular disease (CVD). Aims and Objectives: To study prevalence, frequency and risk factors of Non-alcoholic fatty liver disease in Type 2 Diabetes patients. Methodology: A cross-sectional observational study was conducted on 150 known cases of T2DM (duration &gt;3 years) in the age group of 25-84 years, attending the tertiary teaching hospital. Results: The prevalence of NAFLD in T2DM was found to be 57%. Various risk factors such as hypertension, dyslipidemia, obesity and sleep apnea were found to be associated with NAFLD and T2DM. Conclusion: Glycemic control and duration of diabetes mellitus are important risk factors for the development of NAFLD in T2DM patients

Central diabetes insipidus: a late sequela of BNT162b2 SARS-CoV-2 mRNA vaccine?

BackgroundThe development of an effective vaccine is a powerful tool to contain the global spread of coronavirus disease 2019 (COVID-19). Still, it raises potential safety concerns about the subsequent enhancement of associated immunopathology. Increasing evidence shows that the endocrine system, including the hypophysis, may be involved in COVID-19. Moreover, occasional but increasing reports of endocrine disorders involving the thyroid have been reported after the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. Among them, a few cases encompass the pituitary. Here we report a rare case of central diabetes insipidus following SARS-CoV-2 vaccination.Case presentationWe report a 59-year-old female patient with a 25-year history of Crohn's disease in long-term remission, who presented with sudden onset of polyuria eight weeks after administration of an mRNA SARS-CoV-2 vaccination. Laboratory evaluation was consistent with isolated central diabetes insipidus. Magnetic resonance imaging displayed involvement of the infundibulum and the posterior hypophysis. Eighteen months after the vaccination, she is still under desmopressin treatment and had stable pituitary stalk thickening on magnetic resonance imaging. Although Crohn's disease-associated hypophysitis has been reported, it is scarce. In the absence of other recognizable causes of hypophysitis, we believe the involvement of the hypophysis in our patient may have been triggered by the SARS-CoV-2 vaccine.ConclusionsWe report a rare case of central diabetes insipidus potentially associated with SARS-CoV-2 mRNA vaccination. Further studies are needed to understand better the mechanisms underlying autoimmune endocrinopathies development in the context of COVID-19 infection and SARS-CoV-2 vaccination.

Efficacy of Oral versus Intratympanic Steroids in the Treatment of Idiopathic Sudden Sensorineural Hearing Loss: A 1-year Randomized Control Trial

Background: Sudden sensorineural hearing loss (SSNHL) is a common otologic emergency, with hearing loss of 30 dB or greater at three contiguous frequencies, and an abrupt onset within 3 days or fewer, with no recognizable cause. Aims and Objectives: In this study, the efficacy of intratympanic (IT) injections of dexamethasone are compared with oral prednisolone and the behaviour of the different audiometric curves in response to both the steroid therapies in studied. Materials and Methods: Patients presenting with SSNHL to the Department of ENT, Head and Neck Surgery at Government Multi Speciality Hospital, Chandigarh, were subjected to routine tests. Informed written consent was taken from each patient, and cases meeting the selection criteria were included in the study. Pure-tone audiometry was done before starting treatment. Patients were randomly assigned into two groups based on their enrollment number. Those in Group 1 were treated with three doses of 0.3–0.6 mL IT injections of dexamethasone (4 mg/mL) on alternate days and those in Group 2 received OP 1 mg/kg/day with tapering doses. Pure-tone audiogram (PTA) will be repeated after 2 weeks, 4 weeks, and 8 weeks from the first dose. Results: In the IT dexamethasone group, the pretreatment PTA was 61.05 dB while the posttreatment PTA was 37.45 dB. The hearing gain was 23.6 dB. In the oral steroid group, pretreatment PTA was 66.79 while posttreatment PTA was 47.36 dB. The hearing gain was 19.43 dB. The hearing gain in both the groups was statistically significant; however, there was no statistical difference between the two in terms of superiority of efficacy (P &gt; 0.05). Conclusion: The treatment of SSNHL still remains a challenge among the otologists. The present study establishes that the efficacy of IT steroids was as good as the oral steroid therapy for the management of SSNHL as both the modalities showed significant hearing improvement. Hence, IT steroid can be used as a first-line therapy in patients with. Our study also uncovered the fact that patients who come with shorter duration of onset recover quickly compared to those patients who delay their treatment. Hence, IT steroid can be used as a primary modality of treatment instead of a salvage therapy in the selected group of patients.

Metabolic effects of prolactin.

Over the last years, the metabolic role of PRL has emerged. PRL excess is known to promote weight gain, obesity, metabolic syndrome, and impairment in gluco-insulinemic and lipid profiles, likely due to the suppression of physiologic dopaminergic tone. Prolactin receptors and dopamine receptors type 2 have been demonstrated to be expressed on both human pancreatic β- cell and adipocytes, supporting a key role of prolactin and dopamine in peripheral metabolic regulation. Medical treatment with the dopamine agonists bromocriptine and cabergoline has been demonstrated to decrease the prevalence of metabolic syndrome and obesity, and significantly improve gluco-insulinemic and lipid profiles. In hyperprolactinemic men with concomitant hypogonadism, correction of hyperprolactinaemia and testosterone replacement has been proven to restore metabolic impairment. In turn, low prolactin levels have also been demonstrated to exert a detrimental effect on weight gain, glucose and lipid metabolism, thus leading to an increased prevalence of metabolic syndrome. Therefore, PRL values ranging from 25 to 100 mg/L, in absence of other recognizable pathological causes, have been proposed to represent a physiological response to the request for an increase in metabolic activity, and nowadays classify the so-called HomeoFIT- PRL as a promoter of metabolic homeostasis. The current review focuses mainly on the effects of hyperprolactinemia and its control by medical treatment with DAs on the modulation of food intake, body weight, gluco-insulinemic and lipid profile. Furthermore, it provides the latest knowledge about the metabolic impact of hypoprolactinemia.

Genotypic and phenotypic spectrum of cytosolic phosphoenolpyruvate carboxykinase deficiency.

Pathogenic biallelic variants in PCK1 coding for the cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) cause PEPCK-C deficiency, a rare disorder of gluconeogenesis presenting with hypoglycemia, lactic acidosis, and hepatopathy. To date, there has been no systematic analysis of its phenotypic, biochemical, and genetic spectrum. All currently published individuals and a novel patient with genetically confirmed PEPCK-C deficiency were included. Clinical, biochemical, and genetic findings were analyzed. Protein and in-silico prediction score modeling was applied to analyze potential variant effects. Thirty-two individuals from 25 families were found, including one previously unreported patient. The typical biochemical pattern was hypoglycemia triggered by catabolic situations, elevated urinary concentrations of tricarboxylic acid cycle metabolites, mildly elevated alanine and aspartate aminotransferase and elevated lactate concentrations in serum. Plasma glutamine concentrations were elevated in some patients and may be a suitable marker for newborn screening. With adequate treatment, biochemical abnormalities usually normalized following a hypoglycemic episode. Symptom onset usually occurred in infancy with a broad range from neonatal age to adulthood. Regardless of the genotype, different phenotypes with a broad clinical spectrum were found. To date, eight genotypes with nine different PCK1 variants were identified, of which alleles with the recurrent variant c.925G > A; p.(Gly309Arg) are predominant and appear to be endemic in the Finnish population. Protein modeling suggests altered manganese- and substrate-binding as superordinate pathomechanisms. Environmental factors appear to be the main determinant for the phenotype in patients with biallelic variants in PCK1. Based on the biochemical pattern, PEPCK-C deficiency is a recognizable cause of childhood hypoglycemia. It is a treatable disease and early diagnosis is important to prevent metabolic derailment and morbidity. Newborn screening can identify at least a sub-cohort of affected individuals through elevated glutamine concentrations in dry blood.

Recent advances in the management of transient ischemic attacks.

Transient ischemic attack (TIA) constitutes an important clinical condition, indicating the presence of considerable risk for a subsequent ischemic stroke. Its prompt diagnosis and management have the potential for reducing the risk of neurologic disability, highlighting the critical need to prioritize the care of patients with TIA. The risk of ischemic stroke following a TIA is directly related to its etiopathogenesis, and recognizable causes are commonly categorized within one of three domains: cerebrovascular pathology, cardiac dysfunction, and hematologic disorders. Therefore, the clinical approach to patients suspected of having suffered a TIA demands a comprehensive evaluation, including testing of possible etiologic conditions in all three of these domains, best carried out in an expedited fashion since the stroke risk is greatest in the hours and days that follow the index event. The present is a review of the existing literature addressing the diagnosis, evaluation, prioritization, and management strategies available to clinicians who provide care to patients with TIA.

The many faces of cryptogenic organizing pneumonia (COP).

Organizing pneumonia (OP) is interstitial pneumonia with an acute or subacute clinical course and a histological pattern compatible with acute lung injury. It usually arises after a recent infection of the peripheral bronchial system, whereby is called secondary OP. However, often OP arises with no recognizable cause for which it is called cryptogenic organizing pneumonia (COP). From a radiological standpoint, COP exhibits different imaging appearances and this review makes radiologists and clinicians familiar with the entire spectrum of expected disease findings. Successful interpretation of imaging is pertinent for a rapid diagnosis of COP and knowledge of the entire spectrum of imaging findings in COP is mandatory.

Dysregulated Retinoic Acid Signaling in the Pathogenesis of Pseudoexfoliation Syndrome

Pseudoexfoliation (PEX) syndrome, a stress-induced fibrotic matrix process, is the most common recognizable cause of open-angle glaucoma worldwide. The recent identification of PEX-associated gene variants uncovered the vitamin A metabolic pathway as a factor influencing the risk of disease. In this study, we analyzed the role of the retinoic acid (RA) signaling pathway in the PEX-associated matrix metabolism and evaluated its targeting as a potential candidate for an anti-fibrotic intervention. We provided evidence that decreased expression levels of RA pathway components and diminished RA signaling activity occur in an antagonistic crosstalk with TGF-β1/Smad signaling in ocular tissues and cells from PEX patients when compared with age-matched controls. Genetic and pharmacologic modes of RA pathway inhibition induced the expression and production of PEX-associated matrix components by disease-relevant cell culture models in vitro. Conversely, RA signaling pathway activation by natural and synthetic retinoids was able to suppress PEX-associated matrix production and formation of microfibrillar networks via antagonization of Smad-dependent TGF-β1 signaling. The findings indicate that deficient RA signaling in conjunction with hyperactivated TGF-β1/Smad signaling is a driver of PEX-associated fibrosis, and that restoration of RA signaling may be a promising strategy for anti-fibrotic intervention in patients with PEX syndrome and glaucoma.

Update on idiopathic anaphylaxis.

Idiopathic anaphylaxis (AI) refers to anaphylaxis without a recognizable cause after a comprehensive allergic workup. The diagnostic approach usually includes an accurate clinical history aimed at excluding both the most and the less frequent causes of anaphylaxis and all pathologies that may resemble anaphylaxis. AI is more common in adults than in children. The epidemiology of AI has been reduced in recent years, probably to increase knowledge and discover new clinical entities, such as the α-gal anaphylaxis. Anaphylaxis results from the massive activation of the mast cells (MCs). Thus, it is also necessary to exclude MC disorders, such as mastocytosis and mast cell activation syndrome, and α-tryptasemia, which may manifest with IA symptoms.

Вроджена цитомегаловірусна інфекція: рекомендації ICCRG та аспекти менеджменту, що знаходяться на етапі клінічних випробувань

Вроджена цитомегаловірусна (ЦМВ) інфекція залишається причиною сенсоневральної втрати слуху і аномалій розвитку нервової системи у новонароджених в розвинених країнах світу, що рідко діагностується. Відсутність уніфікованих рекомендацій негативно відбивається на глобальних зусиллях знизити частоту вроджених аномалій, асоційованих із ЦМВ. Власні катамнестичні спостереження за дітьми з мальформаціями нервової системи і сенсоневральними порушеннями, а також оцінка імунологічної відповіді на ЦМВ у вагітних і в період новонародженості ініціювали проведення поглибленого аналізу сучасної світової літератури. У статті подані напрямки мінімізації ризику вродженої цитомегаловірусної інфекції, що реалізуються в клінічних рекомендаціях, заснованих на висновках провідних світових експертів з виявлення та менеджменту вродженої цитомегаловірусної інфекції у вагітних і новонароджених, також окреслені перспективи менеджменту, що знаходяться на етапі клінічних випробувань.