Clinical Picture Research Articles

Clinical Case of Rare Genetic Disorder (Proud Syndrome) in a Child

Background. Proud syndrome is rare inherited disease with X-linked inheritance associated with mutations in the homeobox gene ARX. Typical clinical signs of this syndrome are severe mental retardation, intractable epilepsy, agenesis (dysgenesis) of corpus callosum. Less common features are genital abnormalities, microcephaly, facial dysmorphia, and skeletal malformations. Clinical case description. The article describes the clinical findings of Proud syndrome in girl A., admitted to Children’s City Clinical Hospital No. 1 in Nizhny Novgorod. The girl was born without asphyxia at term through natural vaginal delivery after the first uneventful pregnancy. Body weight at birth was 2600 g. The genealogical history is burdened by the presence of epilepsy in girl’s father relatives. There were no deviations in psychomotor skills development before disease onset. Hemi-convulsive seizures (switching sides) have appeared at the age of 6 months. These attacks had status course and were resistant to anticonvulsant therapy. Neuroimaging has revealed agenesis of corpus callosum. Regression of psychomotor development, new behavioral disorders (stereotypes and auto-aggression), hyperexcitability, and sleep disorders were observed in dynamics. The diagnosis of Proud syndrome was confirmed by identification of probably pathogenic mutation in the ARX gene (c.1111C>T, p. Arg 371*64). The features of anticonvulsant management were demonstrated in the patient. Conclusion. This clinical case presents typical clinical picture of Proud syndrome. The disease is non-curable. Such patients should be administered with syndromic therapy: constant anticonvulsant therapy, correction of behavioral disorders (classes with specialist on mental defects), neurologist, epileptologist, psychiatrist observations. Parental examination is crucial ARX mutation search in order to determine the prognosis for further child-bearing (parents refused to perform genetic study at the time of article writing).

Profile of adult -onset epilepsy in Zagazig university hospitals

BackgroundEpilepsy has many neurobiological consequences. This study aimed to identify the profile of adult patients with new onset epilepsy in our university hospitals as regarding clinical picture, etiology, cerebral imaging and electroencephalogram (EEG) correlation, comorbidities, management, drug therapy and seizure severity and quality of life. We recruited one hundred patients with adult onset epilepsy, and we assessed them clinically, radiologically, and electrophysiologically. We performed Liverpool Seizure Severity Scale (LSSS) to assess seizure severity and the Quality of Life In Epilepsy-10 Questionnaire (QOLIE-10) to assess quality of life of adult patients with new onset epilepsy.ResultsFifty-seven percent of the studied patients were males, and 43.0% were females with mean (± SD) of age was 52.83 (± 17.33), 13.0% of the studied patients had positive family history of epilepsy. 32.0% had focal epilepsy, and 68.0% had generalized epilepsy, 53% of patients had uncontrolled seizures, 49% of patients were on monotherapy, and 51.0% were on polytherapy. The mean (± SD) seizure frequency per month in the studied patients was 4.0 (± 3.15). Imaging abnormalities were found in 88% of studied patients. 43% of the studied patients had abnormal EEG. Post-traumatic epilepsy, focal cortical dysplasia and mesial temporal sclerosis were statistically significant higher in male patients than female patients. Arteriovenous malformations were significantly higher in females. Middle-aged adults’ group had hypertension more than other age groups, older adult age group had atrial fibrillation, coronary heart disease, diabetes mellitus and dyslipidemia more than other age groups. Young adults had migraine more than other age groups. Post-stroke epilepsy was higher in older adult and middle-aged adult groups more than young adult age group. Intracranial neoplasms were higher in older adult age group than other age groups. Patients with moderate, severe, and very severe LSSS score had significantly more frequent uncontrolled seizures, abnormal EEG and higher rate of polytherapy as compared to those with mild LSSS score. Patients with impaired quality of life had more seizure frequency, less seizure control, higher seizure severity, more EEG abnormalities and were mostly treated by AEDs polytherapy than those with average life quality.ConclusionsLevetiracetam was the most preferred drug for treating patients with adult-onset epilepsy (40%), whether used as monotherapy or in combination with other drugs. Seizure severity, and seizure frequency per month strongly impaired patients’ quality of life.

Apert syndrome: modern aspects of diagnosis and treatment

The purpose of this review is to raise awareness of medical professionals about the features of the clinical picture, the possibilities of diagnosis (including prenatal) and therapy of patients with Apert syndrome to further improve the prognosis and improve the quality of life. Acrocephalosyndactyly is a group of rare congenital syndromes characterized by the presence of acrocephaly, craniofacial anomalies, syndactyly of the hands and feet. According to the literature, the most common form of аcrocephalosyndactyly is Apert syndrome (acrocephalosyndactyly type I, Apert syndrome, ICD 10 Q 87.0, OMIM 101200). This is a genetic disease inherited by an autosomal dominant type. CA is caused by a mutation of the fibroblast growth factor receptor type 2 gene (FGFR2) located on the long arm of chromosome 10, which leads to increased bone metabolism and impaired bone synthesis. The frequency of Apert syndrome is about 15 cases per 1,000,000 live births. Wheaton first reported this pathology in 1894, and in 1906 the French pediatrician Eugene Apert published a series of nine clinical cases with a characteristic triad of symptoms. Apert syndrome is characterized by craniosynostosis, bilateral symmetrical limb syndactyly and dysmorphic facial features. Hypoplasia of the upper jaw and bicoronal synostosis are two noticeable craniofacial defects that lead to a flat, deepened appearance of the forehead and the middle part of the face. Hypertelorism and excessive orbitality, low-set ears, flat nose and cleft palate are often found. Cardiovascular, neurological and genitourinary abnormalities may be present. Diagnosis is based on clinical criteria and molecular genetic testing. There is a possibility of prenatal detection of Apert syndrome.

The effect of earthquake on fibromyalgia: a comparison of patients on medication and without medication.

Stressful events like earthquakes might worsen the symptoms of fibromyalgia, although the influence of medications on these consequences is yet uncertain. The objective of this study was to examine the influence of an earthquake on the symptoms of fibromyalgia and evaluate the impacts of medications used to treat fibromyalgia on the clinical picture. Ninety-five fibromyalgia patients were enrolled in a comparative study and divided into two groups: medication and non-medication. Three subcategories of medication groups were established: selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and gabapentinoid drugs (GDs). Before and after the earthquake, clinical evaluations were conducted using the Fibromyalgia Impact Questionnaire (FIQ), Hospital Anxiety and Depression Scale (HADS), and Jenkins Sleep Rating Scale (JSS). Statistical analyses were conducted to compare the scores before and after the earthquake and evaluate the differences between the groups. Statistically significant increases were observed in FIQ, HADS-anxiety, HADS-depression, and JSS scores in the medication and non-medication groups before and after the earthquake comparisons (p < 0.05). Non-medication group reported significantly higher post-earthquake changes in FIQ, HADS-anxiety, HADS-depression, and JSS compared to the medication group (p < 0.05). While HADS-anxiety, HADS-depression, and JSS changes after the earthquake differed according to the drug subgroups (p < 0.05), no statistically significant difference was observed in FIQ values (p > 0.05). The highest scores were detected in the GD subgroup. This study highlights the substantial impact of earthquakes on fibromyalgia patients. Medication use may assist in reducing the detrimental effects of stresses like earthquakes on fibromyalgia symptomatology. Future research with larger sample sizes and more extended follow-up periods is needed to explain these findings and optimize treatment regimens for fibromyalgia patients experiencing significant stressors.

Herpes Simplex Virus Dacryoadenitis Preceding Skin Vesicles.

Herpes simplex virus involvement of the orbit is rare. We report the case of an immunocompetent patient who presented with preseptal edema, erythema, decreased vision, and dacryoadenitis prior to the appearance of vesicular skin lesions and in the absence of corneal dendrites. The patient's clinical picture failed to improve on empiric therapy with intravenous antibiotics. The patient subsequently developed skin vesicles and a nucleic acid amplification swab of the ocular surface was positive for herpes simplex virus-1. The patient demonstrated rapid clinical improvement after initiation of oral antivirals. This is an unusual case of presumed herpes simplex virus dacryoadenitis preceding skin vesicles in an immunocompetent patient.

Metabolomics in Children Cow’s Milk Protein Allergy: Possible Contribution from a System Biology Approach?

One of the most frequent triggers of food anaphylaxis in pediatric age but also among the most common, early, and complex causes of childhood food allergy is cow’s milk protein allergy (CMPA). The diagnostic course and management of this allergy is defined in a complex clinical picture due to several factors. First of all, the epidemiological data are not uniform, mainly as a consequence of the diagnostic methodology used in the various studies and the different age ranges covered. In addition, there is the complexity of terminology, since although CMPA traditionally refers to immune-mediated reactions to cow’s milk, it is a term encompassing numerous clinical features with different symptoms and the requirement for specific treatments. Moreover, the differential diagnosis with other very frequent diseases, especially in the first year of life, such as gastro-esophageal reflux disease or colic, is still complex. This can result in misdiagnosis and incorrect treatment, with harmful health consequences and significant economic repercussions. In this context, the combination of several omics sciences together, which have already proved useful in clarifying the allergenicity of cow’s milk proteins with greater precision, could improve the diagnostic tests currently in use through the identification of new, more specific, and precise biomarkers that make it possible to improve diagnostic accuracy and predict the patient’s response to the various available treatments for the recovery of tolerance.

A clinical case of an atypical clinical pattern of renal colic in a nonverbal patient

Renal colic is a condition caused by the passage of a concretion from the kidney through the ureter into the bladder, which is accompanied by a pronounced pain syndrome. Patients with renal colic often seek emergency help with complaints of severe pain, nausea, dysuria. However, there is a category of people who, for various reasons, cannot verbally express their feelings. Such patients are called nonverbal. Nonverbal patients are people with severe cognitive impairments or those who are temporarily unable to speak due to surgery or illness, but they can still demonstrate pain using nonverbal signals.In this article, we present an observation of an atypical clinical picture of renal colic in a nonverbal elderly patient. In the observed woman, an acute attack of renal colic lasted 5 days and passed first under the «mask» of acute pancreatitis. Without receiving pathogenetic therapy, the patient developed acute obstructive pyelonephritis, septic shock, which was initially mistaken for an acute violation of cerebral circulation. The performed computed tomography (CT) helped to identify a concretion in the upper third of the ureter on the left, a violation of the outflow of urine from the left kidney. The patient urgently had a stent installed in the pelvis of the left kidney, urine outflow was restored, anti-inflammatory, detoxification, litolytic therapy was prescribed. After that, the patient's condition improved significantly, and after 3 months, a decrease in the size and fragmentation of the concretion was observed during the control CT scan.Conclusion. Nonverbal patients are a special group of patients whose clinical picture may be blurred or atypical. Assessment of pain symptoms in nonverbal patients is difficult, which can lead to an incorrect diagnosis and lengthen the period of diagnosis of the disease. The timely diagnosis of renal colic in nonverbal patients is also affected by the localization of pain, since its irradiating nature can direct the diagnostic search «on the wrong track».

OTULIN deficiency: focus on innate immune system impairment

OTULIN deficiency is a complex disease characterized by a wide range of clinical manifestations, including skin rash, joint welling, lipodystrophy to pulmonary abscess, and sepsis shock. This disease is mechanistically linked to mutations in the OTULIN gene, resulting in an immune disorder that compromises the body’s ability to effectively combat pathogens and foreign stimuli. The OTULIN gene is responsible for encoding a deubiquitinating enzyme crucial for hydrolyzing Met1-poly Ub chains, and its dysfunction leads to dysregulated immune responses. Patients with OTULIN deficiency often exhibit an increase in monocytes, including neutrophils and macrophages, along with inflammatory clinical features. The onset of symptoms typically occurs at an early age. However, individuals with OTULIN haploinsufficiency are particularly susceptible to life-threatening staphylococcal infections. Currently, the most effective treatment for patients with OTULIN biallelic mutations involves the use of TNF-blocking agents, which target the dysregulated immune response. In conclusion, OTULIN deficiency presents a complex clinical picture with diverse manifestations, attributed to mutations in the OTULIN gene. Understanding the underlying mechanisms is crucial for developing targeted therapeutic interventions to address this challenging condition. Further research into the pathophysiology of OTULIN deficiency is essential for improving clinical management and outcomes for affected individuals.

Pneumoperitoneum Due to Spontaneous Uterine Perforation Caused by Pyometra – A Rare Finding and a Diagnostic Challenge

Background: Spontaneous perforation of uterus resulting in generalized peritonitis in postmenopausal women is a very rare entity usually caused by pyometra and is associated with high morbidity and mortality. The clinical picture of uterine perforation secondary to pyometra are similar to hollow viscus perforation which makes preoperative diagnosis difficult. A correct and definitive diagnosis can be made with laparotomy or laparoscopy. Case: We report a case of 64-years-old female patient who presented with pain abdomen and distension and inability to pass flatus/motion with signs suggestive of acute generalised peritonitis and genital prolapse with pneumoperitoneum underwent Total Abdominal Hysterectomy with bilateral salpingo-oophorectomy. Results: Despite the surgical intervention, Total Abdominal Hysterectomy with bilateral salpingo-oophorectomy and use of several antibiotics, this patient did not improve and died post-operatively. Conclusions: This case report aim for awareness of the many etiologies for peritonitis is of great importance and to alert the surgeons to the possibility that uterine perforation secondary to pyometra also shows air under diaphragm apart from hollow viscus perforation. Correct diagnosis and proper treatment are essential for survival of patients.

The Role of microRNA in the Regulation of Cortisol Metabolism in the Adipose Tissue in the Course of Obesity

The similarity of the clinical picture of metabolic syndrome and hypercortisolemia supports the hypothesis that obesity may be associated with impaired expression of genes related to cortisol action and metabolism in adipose tissue. The expression of genes encoding the glucocorticoid receptor alpha (GR), cortisol metabolizing enzymes (HSD11B1, HSD11B2, H6PDH), and adipokines, as well as selected microRNAs, was measured by real-time PCR in adipose tissue from 75 patients with obesity, 19 patients following metabolic surgery, and 25 normal-weight subjects. Cortisol levels were analyzed by LC-MS/MS in 30 pairs of tissues. The mRNA levels of all genes studied were significantly (p &lt; 0.05) decreased in the visceral adipose tissue (VAT) of patients with obesity and normalized by weight loss. In the subcutaneous adipose tissue (SAT), GR and HSD11B2 were affected by this phenomenon. Negative correlations were observed between the mRNA levels of the investigated genes and selected miRNAs (hsa-miR-142-3p, hsa-miR-561, and hsa-miR-579). However, the observed changes did not translate into differences in tissue cortisol concentrations, although levels of this hormone in the SAT of patients with obesity correlated negatively with mRNA levels for adiponectin. In conclusion, although the expression of genes related to cortisol action and metabolism in adipose tissue is altered in obesity and miRNAs may be involved in this process, these changes do not affect tissue cortisol concentrations.

Genotype–Phenotype Correlations in Alport Syndrome—A Single-Center Experience

Background: Alport syndrome (AS) is a common and heterogeneous genetic kidney disease, that often leads to end-stage kidney disease (ESKD). Methods: This is a single-center, retrospective study that included 36 adults with type IV collagen (COL4) mutations. Our main scope was to describe how genetic features influence renal survival. Results: A total of 24 different mutations were identified, of which eight had not been previously described. Mutations affecting each of the type IV collagen α chains were equally prevalent (33.3%). Most of the patients had pathogenic variants (61.1%). Most patients had a family history of kidney disease (71%). The most prevalent clinical picture was nephritic syndrome (64%). One-third of the subjects had extrarenal manifestations, 41.6% of patients had ESKD at referral, and another 8.3% developed ESKD during follow-up. The median renal survival was 42 years (95% CI, 29.98–54.01). The COL4A4 group displayed better renal survival than the COL4A3 group (p = 0.027). Patients with missense variants had higher renal survival (p = 0.023). Hearing loss was associated with lower renal survival (p &lt; 0.001). Conclusions: Patients with COL4A4 variants and those with missense mutations had significantly better renal survival, whereas those with COL4A3 variants and those with hearing loss had worse prognoses.

Lymphocytic hypophysitis - various course of the disease and individualized therapeutic approach. An algorithm of the follow-up.

Lymphocytic hypophysitis (LH) is a rare inflammatory disorder of the pituitary or/and hypothalamus with variable disease course: from spontaneous remission to pituitary atrophy. The diagnosis, treatment and follow-up remain challenging. The aim of the study is to present long-term data and an individualized therapeutic approach and propose an algorithm for the follow-up of patients with probable LH. A retrospective analysis of 18 consecutive adult patients (13 W/5 M, mean age 45.2 years) with LH diagnosed and treated in a tertiary referral center. The first manifestations were headaches (50.0%), polyuria/polydipsia (33.3%) and symptoms of hypopituitarism (16.7%). Somatotropic, adrenal, gonadal and thyroid axis insufficiencies were found in 44.4%, 33.3%, 33.3%, and 27.8% of patients, respectively. Arginine vasopressin deficiency was diagnosed in 8 patients (44.4%). Some of the dysfunctions were transient. Magnetic resonance imaging (MRI) revealed thickened pituitary stalk in all but 2 cases. In 2 patients an anterior pituitary lesion, most likely inflammatory was described. Four patients were given steroids (severe headaches) with clinical recovery and stable/improved MRI. One woman was operated on due to the progressive mass-related symptoms - histopathological examination confirmed LH. In the remaining 13/18 patients watchful waiting approach allowed to obtain hormonal and radiological stabilization/improvement. LH is a disease with a complex clinical picture and challenging diagnosis. Treatment requires an individual approach: vigilant observation is the cornerstone of therapy, with steroid/surgical treatment reserved for cases with mass-related symptoms. Further multicenter research might help in better understanding of the LH and creating standards of care in this rare disease.

Clinical Course of Methylmalonic Aciduria in Siblings: Two Clinical Cases

Background. Methylmalonic aciduria (MMA) is a rare disease from the group of hereditary metabolic diseases. The MMA clinical picture is polymorphic and meanwhile similar to other metabolic disorders. Determination of specific metabolites in biological fluids and molecular genetic testing are crucial to diagnose this disease. Timely diagnosis mainly determines the treatment efficacy and, therefore, the prognosis of MMA development. Clinical case description. Two siblings with MMA caused by methylmalonyl-CoA mutase deficiency (OMIM #251000) have shown duplication chr6-49459106-T-TA: NM_000255.4c.360dupT (p.Lys121fs) in homozygous state in exon 2 of the MMUT gene. The disease was diagnosed in the first child with underlying metabolic crisis that finally led to irreversible changes in organs and systems and lethal outcome. The diagnosis in the second child was established antenatally, thus, therapy was initiated from the first day of life. Favorable clinical course of the disease was observed during 5 months of follow-up. Conclusion. Timely MMA diagnosis (antenatal or during neonatal screening) is crucial for effective management and relatively favorable life prognosis for infants.

New Biomarker Candidates of Sepsis: Diagnostic and Prognostic Value of Presepsin, Angiopoietin 1 and 2

Objective: Sepsis is an uncontrolled inflamatory response that occurs in the body towards infection. It’s an important clinical picture that is seen in high morbidity and mortality so early diagnose and treatment areimportant. For that reason, for the septic cases to get early diagnosis and to predict the prognosis, new biomarkers are needed nowadays. Presepsin, angiopoietin 1 and angiopoietin II are biomarkers that are not usedroutinely yet, in our study, according to the new description given in Sepsis 3 meeting, in cases that are diagnosed with sepsis, we aimed at comparing diagnostic and prognostic values of these biomarkers. Methods: In our study, there were two groups. Patient group consisting of 48 cases with 33 men and 15 women and control group consisting of 42 cases with 23 men and 19 women. Control group is selected within patient relatives with similarities of age and sex. Demographic datas, accompanying diseases, APACHE II, SAPS and SOFA scores counted in the first 24 hours, leukocyte count, eritrocyte sedimentation rate, C-reactive protein, procalcitonin value, culture sampling results (blood, urine, sputum, endotracheal aspirate) that are measured in their stays, 7th and 28th day mortality counts after their ICU stays are written down. Presepsin, angiopoietin I and angiopoietin II are detected by sandwich ELISA method. Results: According to demographic features there isn’t any significant statistical difference between the patient group and the control group (p&gt;0.005). In patient group Presepsin, angiopoietin I and angiopoietin II values were statistically high significantly compared to the control group (p&lt;0.001). After the evaluation, serumpresepsin value noticed that has a diagnostic value in the diagnosis of sepsis (EAA: 0.74, 95%GA: 0.64–0.85, p&lt;0.001). The suggested border value for this value is predicted as 0.47, 73%sensitivity and 62% specificity are determined. Serum angiopoietin I value noticed that has a diagnostic value in the diagnosis of sepsis (EAA: 0.80, 95%GA: 0.71–0.89, p&lt;0.001). The suggested border value for this value is predicted as 178.24, 69% sensitivity and 69% specificity are determined. Serum angiopoietin II value noticed that has a diagnostic value in the diagnosis of sepsis (EAA: 0.89, 95% GA: 0.82–0.95, p&lt;0.001). The suggested border value for this value is predicted as 77.56, 84% sensitivity and 83% specificity are determined. Conclusions: In our study, presepsin, angiopoietin I and angiopoietin II values are determined as statistically high according to healthy control group and are found successful with high sensitivity and specificity in diagnosing. Presepsin, angiopoietin I and angiopoietin II values in septic patients are found successful with high sensitivity and specificity at 7th and 28th days mortality prediction.

Abstract PO1-20-08: Primary breast implant-associated squamous cell carcinoma with subsequent TEMPUS testing and failure of immunotherapy

Abstract Primary squamous cell carcinoma of the breast is a rare entity, and there are a limited number of cases in the literature describing squamous cell carcinoma arising from breast implants. It has been hypothesized that these implant-associated cancers may arise from epithelialization of the implant capsule followed by chronic inflammation. None of the cases in the literature were treated with immunotherapy. We present a case of an aggressive, primary sarcomatoid squamous cell carcinoma of the breast arising from a breast implant that was treated unsuccessfully with simultaneous chemotherapy and immunotherapy following TEMPUS testing. Introduction: Breast augmentation is the most common plastic surgery procedure performed worldwide, with more than 300,000 done in the United States every year. While breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is extensively discussed in recent literature, other breast implant-associated cancers are rarer and less studied. Breast implant-associated squamous cell carcinoma (BIA-SCC) specifically is an extremely rare complication of breast augmentation and no guidelines for treatment exist. The American Society of Plastic Surgeons (ASPS) released a statement on BIA-SCC on 9/2022 following a safety communication from the FDA, and it is recommended health care providers submit case reports of BIA-SCC to a patient registry. Case study: We present the case of a female patient who underwent bilateral breast augmentation in 2006 with Mcghan textured, pre-pectoral, areolar saline implants. In 2022, she presented with swelling and a lump in her breast and underwent bilateral breast implant removal with capsulectomy. Pathology showed triple negative sarcomatoid squamous cell carcinoma of the right breast capsule. TEMPUS testing on the breast biopsy revealed a PIK3CA mutation and PD-L1 negative status. Her case was discussed with a multi-disciplinary team including plastic surgery, multiple oncologists, and radiation oncology and her clinical picture was determined to be most consistent with BIA-SCC. Based on the KEYNOTE-522 study, she was determined to be a candidate for neoadjuvant therapy with pembrolizumab and chemotherapy as she was newly diagnosed, previously untreated, nonmetastatic, and had a triple negative tumor. She received two cycles of carboplatin, paclitaxel, and pembrolizumab but unfortunately rapidly progressed with chest wall extension, multiple new pulmonary nodules, worsening lymphadenopathy, right ventricular tumor thrombus, and new malignant pleural effusion and was transitioned to hospice. Discussion: Seven cases of BIA-SCC, one case of squamous cell carcinoma (SCC) after liquid silicone injection augmentation, one case of squamous metaplasia on the breast implant capsule, and one case of epithelization of the breast implant capsule have been previously described in the literature (Table 1). None of the available cases of BIA-SCC report TEMPUS testing, and none of the patients were treated with immunotherapy. The origin of BIA-SCC is unclear, but several theories have been described including chronic inflammation leading to conversion of epithelial tissue on the capsule to SCC. It is unknown how the breast implant capsule might become epithelialized to begin with – introduction of epithelium intraoperatively during augmentation, rupture of epidermal cysts, existence of epithelium in the area from a childhood injury or from birth, or epithelization from chronic shear forces from the augmentation or leakage of the implant are all possibilities. With the ongoing data gathering through the FDA patient registry, we will continue to learn more about these rare cancers and potentially get further insight into their origins. Table 1 An overview of cases of BIA-SCC in the literature Citation Format: Emily Podany, Katherine Clifton. Primary breast implant-associated squamous cell carcinoma with subsequent TEMPUS testing and failure of immunotherapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-20-08.

Concurrent congenital hemophilia B and acquired hemophilia A: a unique case report.

Congenital hemophilia B is a rare X-linked recessive bleeding disorder caused by factor IX deficiency. Acquired hemophilia A is a rare, acquired bleeding disorder that presents with new-onset bleeding, especially in older adults, due to the development of auto-antibodies against factor VIII (FVIII). This case report presents the medical management of a patient with congenital hemophilia B and acquired hemophilia A. We highlight the limitations of maintaining factor levels with factor replacement therapy alone, particularly in hemophilia patients who have developed factor inhibitors. In addition, we draw attention to the need for dose escalation, the cost, and the need for immune-tolerance induction therapy. This case illustrates that when the current diagnosis does not explain the full clinical picture and laboratory data are inadequate, it is important to continue to seek alternative diagnoses and cost-effective treatment.

Acute coronary syndrome in elderly and senile diabetic patients

Acute coronary syndrome (ACS) remains a common cause of hospitalization in diabetes mellitus (DM) patients. It is believed that diabetic neuropathy patients have a high atypical course incidence of acute coronary syndrome, because of the frequent neuropathy development in diabetes patients, but the data on this are quite contradictory. Aim: The study aimed to determine the features of the pain syndrome and its severity in ACS and concomitant diabetes patients. Materials and Methods: The study involved 36 diabetes patients (22 men and 14 women) aged 62-86 years, hospitalized urgently for ACS. Pain syndrome was assessed during hospitalization and immediately after coronary artery revascularization using the following criteria: visual analogue scale (VAS), Numerical Rating Scale (NRS), clinical data, and biochemical markers. Results: Most of the patients (91.67%) complained of chest pain at the time of hospitalization, the rest were not bothered by any pain. Patients described pain as “burning” (30.56 %), “squeezing” (30.56 %), “tightness” (25.0 %), and “tingling” (5.56 %). There were also complaints of difficulty breathing (13.89 %), shortness of breath (11.1 %), and palpitations (41.67 %). The appearance of excessive sweating was noticed by 16.67% of patients. There was no statistically significant difference between the results of VAS and NRS pain scores (p &gt; 0.1). The mean blood glucose level at hospitalization was 8.19±3.45 mmol/l (in men – 8.17±3.61 mmol/l, in women – 8.28±3.13 mmol/L). Glycemia level higher than 10.0 mmol/l was detected in 8 patients, which accounted for 22.22% of all patients. Severe pain syndrome patients dominated in this category (62.5 %). Conclusions: In patients with myocardial infarction and diabetes, the typical clinical picture of ACS prevailed (91.67% of patients) over the painless form. Before revascularization, moderate to severe pain occurred with equal frequency; there were no statistical differences between blood pressure, heart rate, and blood glucose level (p&gt; 0.1) in patients with severe and moderate pain. Hyperglycemia (≥10.0 mmol/l) was detected in 22.22% of patients, among whom severe pain syndrome patients prevailed. _________________________________________________________________________________________ Keywords: elderly patients; diabetes mellitus; acute coronary syndrome; pain syndrome

Chest pain as an interdisciplinary problem – emphasis on somatoform disorders

Chest pain of a non-cardiac nature is one of the extremely significant problems of clinical medicine, which is associated with the widespread prevalence of this condition and the high healthcare costs for diagnosing and treating such patients. Along with neurological, gastroenterological and pulmonological diseases, mental disorders make a major contribution to the formation of chest pain. Moreover, the formation of pain in the chest area can be associated not only with such well-known psychopathological conditions as depression and anxiety disorders, but also with the pathology of the somatoform circle. This review presents data on the frequency of chest pain associated with mental disorders (pain as a symptom of a mental disorder, mental disorders as a consequence of a previous episode of chest pain, etc.), the nature of the relationship between pain symptoms and mental disorders, as well as the clinical picture somatoform disorders manifesting in the form of thoracalgia. Information is summarized on approaches to diagnosing mental disorders in patients with chest pain and the possibilities for their psychopharmacotherapy and psychotherapy. When discussing psychopharmacotherapy, emphasis is placed on the possibilities of using the atypical tranquilizer tofisopam in this category of patients, and a brief description of its effectiveness and safety is given. To illustrate the main points of the review, a clinical case of a patient with chest pain of non-cardiac origin, which manifested itself after a traumatic event, which in turn provoked a myocardial infarction, is also presented. Positive dynamics with subsequent recovery during therapy with tofisopam are described.

Prenatal and neonatal phenotype of Larsen of La Réunion Island syndrome (B4GALT7-linkeropathy)

Larsen of La Réunion Island syndrome (LRS) is an autosomal recessive condition associated with multiple large joint dislocations, clubfeet, severe dwarfism, and distinctive facial features. LRS is caused by a recurrent homozygous variant in B4GALT7 gene with a founder effect in La Réunion population. Proteoglycans (PG) that are a major component of the extracellular matrix, are composed of a core protein connected to a glycosaminoglycans side chain via a tetrasaccharide linker region. B4GALT7 encodes galactosyltransferase I, one of the enzymes involved in the biosynthesis of the linker region. Conditions caused by pathogenic biallelic variants in genes implicated in the synthesis of the tetrasaccharide linker of PG are known as linkeropathies.Prenatal features are rarely described in this group of chondrodysplasias. We present a series of 12 unpublished patients having LRS and describe the perinatal phenotype. All the patients had a prenatal growth restriction with brevity of limbs. The other features revealed by ultrasounds were increased nuchal translucency at 10–12 weeks of gestation (50 %), feet abnormalities (clubfeet or metatarsus varus) (25 %), dislocation affecting at least one large joint (elbow, knee, wrist) (25 %). Bilateral bowing of femora was noted for two fetuses. Fibular hypertrophy was noted for one fetus. Prenatal helical computed tomography (CT) performed in three pregnancies showed additional data such as bowing of the forearm bones, proximal radio-ulnar synostosis, or dislocation of large joints. Prenatal sonographic and helical CT findings led to the prenatal diagnosis of LRS in four patients. We confirm that the neonatal clinical picture of LRS has an important overlap with that reported in patients with B4GALT7 deficiency outside La Réunion Island and other linkeropathies. The core of the phenotypic spectrum combines low birth height, micromelia, hypermobility, dislocation of at least one large joint, facial features with prominent eyes, microstomia, depressed nasal bridge, and midface hypoplasia. Other clinical features include clubfeet (33%), bifid thumb in one patient, and cardiac abnormalities in two patients. Radiological findings include radio-ulnar synostosis (75%), metaphyseal flaring, precocious carpal ossification, and a Swedish key appearance of the proximal femora. Finally, we also report radiological features rarely described in B4GALT7-linkeropathies, including bowing of the femora and fibular hypertrophy. Our results confirm the phenotypic continuum of LRS within linkeropathies with some additional findings, including a high frequency of clubfeet usually described in B3GALT6-linkeropathies, the presence of congenital heart diseases usually described in B3GAT3-linkeropathies, and a high frequency of metaphyseal flaring usually reported in B3GALT6 or XITLT1-linkeropathies.This is the first study that describes the perinatal phenotype in a cohort of patients with LRS. This study can help improve the prenatal diagnosis of the linkeropathies and add this group of conditions to the differential diagnosis of chondrodysplasias with multiple dislocations.In view of the founder effect for LRS in La Réunion Island, this disease should be suspected in fetuses with growth restriction and micromelia. Thus in case of LOH which include B4GALT7 identified in SNP-array, we recommend performing a targeted Sanger sequencing for the recurrent mutation c.808C > T; p. (Arg270Cys).

ВРОЖДЕННАЯ АНОМАЛИЯ ЧЕРВЕОБРАЗНОГО ОТРОСТКА, ОСЛОЖНИВШАЯСЯ АППЕНДИЦИТОМ

Congenital malformations of the appendix are an extremely rare pathology, do not have a specific clinical picture and are usually detected at the time of surgery or pathohistological examination of the removed appendix. The purpose of the study. To present a description of a rare pathology – a case of incomplete doubling of the appendix and its atypical location, which contributed to the development of chronic recurrent appendicitis and periappendicitis. Results. The patient, aged 19, was operated on with a diagnosis of acute appendicitis. Laparoscopy has revealed that the appendix is partially retracted into the inguinal hernia and purulent fibrinous periappendicitis occurs. The vermiform appendix was removed. During its examination by both the surgeon and the pathologist, no developmental abnormality was detected. Pathohistological examination revealed incomplete doubling of the appendix. The additional process was located in the thickened mesentery of the main appendix. The complete absence of the outer layer in the muscle membrane and the serous membrane of the accessory process was revealed. This abnormality has provoked the development of chronic recurrent appendicitis and periappendicitis with the formation of an appendicular infiltrate. Conclusion. This article describes a rare clinical case of not only abnormal development of the appendix with the formation of chronic recurrent appendicitis, the formation of periappendicular infiltrate, but also its atypical location – it was partially involved in an inguinal hernia.