Chronic Cerebellar Meningoencephalitis in Adulthood: A Report of a Rare Case.

The development of meningoencephalitis is a result of an inflammation of the meninges and the brain, which can cause neurological sequelae. Cerebellar meningoencephalitis in adult patients is extremely rare and requires special diagnostic approaches. The aim of this report is to present a rare case of meningoencephalitis and evaluate the diagnostic and therapeutic techniques. We present a 45-year-old male patient who has entered the neurosurgery clinic with a severe headache lasting for a month. Neurological status determines intracranial hypertension. Magnetic resonance tomography (MRT) showed evidence of hyperintense lesions with homogenous enhancement in the right hemisphere of the cerebellum. The patient underwent a suboccipital paramedian craniotomy to excise the lesions and for the pathohistological examination of the biopsy material. Biopsy examination found sections expressing an infection process causing chronic meningoencephalitis in the right hemisphere of the cerebellum. The patient was treated postoperatively with cephalothin 2 g every 12 hours for 14 days. Follow-up examinations proved a relief of the symptoms. Meningoencephalitis of the cerebellum and the meninges is a complication that may occur in adulthood, and surgical excision, biopsy examination, and antibiotic therapy are promising methods for managing the disease.

Awake Craniotomy for a Frontal Astrocytoma: A Case Report.

Awake craniotomy is a surgical procedure that has been gaining significance over the past decades. Neuronavigation is an intraoperative technology that locates tumors and monitors the brain cortex during awake craniotomy. The presence of cerebral low-grade gliomas in the frontal lobe creates a risk of affecting vital centers of the brain cortex during surgery. We present a clinical case of a 42-year-old male patient who entered the neurosurgery clinic with a clinical manifestation of headache for two months. MRI showed evidence of the recurrence of a left frontal glioma. Differential diagnoses of frontal gliomas include metastases, abscesses, and cysts. The pathophysiologic background of the disease is the mutation of neuroglial cells, which leads to an abnormal and uncontrollable proliferation. Under sleep-awake anesthesia, operative treatment was performed through left frontal awake craniotomy under neuronavigation. As a result, a total excision was achieved. Motor functions of the right limbs and speech have been preserved. The patient was mobilized on the day after the intervention. Surgery-related complications were not observed. The patient had relief from the symptoms and was discharged on the fifth day. Awake craniotomy combined with neuronavigation was the most efficient and the least harmful method for the excision of the tumor. For low-grade gliomas localized in the frontal area of the encephalon, awake craniotomy is the only secure option for surgery.

Double Trouble: A Case Report on the Surgical Management of Dual Intracranial Metastases.

Intracranial metastasis disease (IMD) has proven to be a frequent secondary occurrence, usually for primary cancers such as lung, breast, and melanoma, which have a high possibility of metastasizing to the brain. Due to the reasons listed above, treatment and early diagnosis are incredibly challenging. In the past decade, medicine has developed much better imaging solutions and radiological and surgical approaches, increasing the postoperative survival prognosis and achieving more time-efficient results. It is still exceptionally difficult to be able to prevent what type of metastasis a patient might develop other than by using the tumor type or subtype. We present a case of a 51-year-old female patient entering the Neurosurgical Clinic at the University Hospital "St. Ivan Rilski" for operative treatment of a second metastatic lesion located on the left parietal lobe in January 2024. She had previously had an operative resection of an initial lesion located on the left temporal lobe in December 2023. Her medical history began in 2015 when her first diagnosis was a breast carcinoma, followed by operative treatment and radio-, chemo-, and targeted therapy. In 2020, due to metastases located in the bones, she had to undergo another treatment with chemotherapy as well as have a total hysterectomy done as a result of another metastasis. The patient did not provide any family history, nor did she confirm any past or current allergies to foods, drugs, etc. Under general inhalation anesthesia, the patient was placed in a park bench position to the right and had a Mayfield head holder applied. Through a left parietal craniotomy and neuronavigation, a tumor formation was revealed with the characteristic of a secondary lesion. A gross total resection was achieved through a microsurgical technique. Postoperatively, there were no further complications observed in the patient, and she was discharged on day five from the hospital with relief of her symptoms.

Symptomatic Cavum Vergae Cyst in a Geriatric Patient: A Report of a Rare Case and Conservative Management Approach.

Cavum vergae (CV) cysts constitute a small proportion of intracranial cysts, and although generally asymptomatic, there are occasional cases where they might exhibit clinical manifestations. We present a clinical case of a 79-year-old female patient who had a clinical manifestation of headache on the occipital side of the head with irradiation to the shoulder girdle as well as numbness, dizziness, visual impairment, sleep disturbances, and tingling in the hands for three months. Vertigo and rightward staggering had been experienced for two weeks. On physical examination, it was discovered that there was smoothed physiological lordosis, restricted and painful movements, and paravertebral muscle rigidity in the cervical region. The patient had bilaterally reduced biceps and triceps reflexes, painful Erb's points, and hypesthesia over the C5 and C6 dermatomes on the right side. The patient had decreased coordination and displayed staggered movement to the right. A CT scan discovered dilated subarachnoid spaces of the convexity and a CV cyst. The patient was prescribed conservative therapy consisting of etoricoxib oral at a dosage of 2 × 60 mg for seven days, tolperisone hydrochloride orally at a dosage of 2 × 150 mg for seven days, pregabalin 75 mg, one pill in the evening for seven days, ozoid (a gel containing ozone) for external application, and vinpocetine 2 × 10 mg orally for two months. Following the conservative treatment, the patient exhibited improvement in her symptoms and no longer had challenges carrying out her daily tasks. Furthermore, six months after the therapy, the patient did not experience any symptoms. Long-term follow-up will be conducted in cases of symptom recurrence or cyst enlargement.

Botulinum Toxin Type A in the Treatment of Raynaud's Syndrome: A Case Report.

Raynaud's syndrome is characterized by paroxysmal vasospasm in the digital arterioles, following exposure to cold or stress. Pain, swelling, stiffness, and hypoesthesia are observed as manifestations. The presence of a trophic ulcer is accompanied by a range of severe manifestations. The assaults occur in three distinct phases, namely vasospastic, plethoric, and erythema. Various approaches improve the overall well-being of a patient. It is possible to differentiate between primary and secondary Raynaud's syndrome, the latter being linked to systemic diseases. The application of botulin toxin is commonly indicated in several medical conditions including focal dystonia, spasticity with or without contractures, paraparesis in children with cerebral palsy, multiple sclerosis, brain injuries, involuntary muscle hyperactivity of a non-dystonic nature, pain management, strabismus, nystagmus, sialorrhea, and esthetic medicine. When treating Raynaud's a technique is used with injection at the base of each finger, from the palmar side, which helps with cooling and minimizing discomfort for patients. We present a clinical case of a 70-year-old female patient with Raynaud's syndrome in which we have placed 70E distributed to both hands botulin toxin type A. Improvement in the patient's symptomatology was noticed on day 3, with warming of the hands, lack of swelling, and pain with duration of the effect little over three months. The patient underwent a six-month follow-up following the therapy with botulinum toxin type A, and no indications of recurrence or advancement of Raynaud's syndrome (RS) were seen.

Cerebral Calcifications as a Result of Primary Hyperparathyroidism: A Report of a Rare Case.

Primary hyperparathyroidism (PHPT) is an extremely uncommon cause of cerebral calcification. A male patient, aged 45, was admitted to the neurosurgery clinic with a closed traumatic brain injury, namely a concussion, resulting in symptoms of headache and loss of balance. A CT scan was conducted, which detected bilateral calcifications on the basal ganglia and the tentorium. The blood tests revealed increased levels of serum calcium, phosphate, and parathyroid hormone (PTH), while vitamin D levels were within the normal range. The patient received symptomatic therapy for the cerebral concussion and was referred for further diagnostic procedures. Based on these exams, it was determined that the patient had a parathyroid adenoma, which was responsible for PHPT characterised by increased levels of calcium, phosphate, and PTH. The patient subsequently underwent a successful parathyroidectomy. Half a year following the surgical procedure, the patient remained free of any indications of neurological conditions, and the levels of PTH and calcium in their body were within the expected range. Whenever trying to identify the cause of cerebral calcification, it is important to explore several possible diagnoses. A possible cause that should be taken into account is PHTP.

Epileptic Seizures in a Pediatric Patient With Vein of Galen Aneurysmal Malformation and Obstructive Hydrocephalus: A Rare Case Report.

The vein of Galen aneurysmal malformation (VGAM) is a rare congenital arteriovenous fistula of the embryonic median prosencephalic vein of Markowski, resulting in its pathological dilation. If left untreated, it can lead to multiple severe complications in the neonatal period, among which obstructive hydrocephalus. We present a case report of a six-year-old male patient with severe status epilepticus and a clinical history of VGAM and obstructive hydrocephalus, diagnosed via an MRI and an MR-angiography. The hydrocephalus was treated via a ventriculostomy at the age of six months, while the VGAM underwent a partial transarterial endovascular embolization when the patient was four years old. The procedures were successful, and there were no significant post-operative complications observed. The epileptic seizures began at a later point and were successfully medicated with valproate. However, they resumed due to a lowering of the medication dosage by the patient's parents. The patient was given a new valproic acid regimen with an appropriate dosage, and his parents reported no further seizures. This case report emphasizes the use of appropriate prenatal and neonatal diagnostic methods for VGAM and explores the nature of the multi-procedural therapy approach towards the pathology and its complications in relation to a possibly idiopathic co-pathology, namely epilepsy.

Anaplastic Transformation of Sphenoid Wing Meningioma With Orbital and Cavernous Sinus Invasion: Unveiling the Aggressive Nature.

Primary tumors in the central nervous system, known as meningiomas, are frequently found and constitute a substantial proportion of tumor cases. Although generally benign, there are occasional cases where they might exhibit malignant characteristics. Anaplastic meningioma is a rare subtype of malignant meningiomas, representing only a small proportion of cases. We present the case of a 70-year-old female patient who presented to the Neurosurgery Clinic of University Hospital "Saint George" with clinical manifestations of monocular vision and blurry vision in the right eye for three months. On physical examination, unilateral ptosis and mydriasis were noted in the left eye. MRI revealed an extra-axial mass located supratentorial in the left temporopolar region affecting the wing of the left sphenoidal bone, invading the cavernous sinus, suppressing the left and right optic nerves, and involving the left orbit. Operative treatment was performed through a left pterional craniotomy and resection of the tumor mass by microsurgical technique. The subdural, epidural, and intraorbital mass were resected. Total removal of the tumor was not achievable and subtotal resection was performed. Pathology results showed that the tumor mass was anaplastic meningioma. Surgery-related complications were not observed. Postoperatively, the patient was mobilized on the day after intervention and the control CT scan showed no ischemic or hemorrhagic events. The patient experienced relief in her symptoms and was discharged on the fifth day. The patient underwent radiation therapy, resulting in the complete removal of the left tumor in the cavernous sinus. After six months, no tumor recurrence was found, and a long-term follow-up is planned to monitor for possible recurrence.

Epidemiological Study of Traumatic Brain and Spinal Injuries in a Pediatric Population: A One-Year Analysis of Prevalence, Causes and Trends.

Background Traumatic brain injury (TBI) and spinal cord injury (SCI) are leading causes of morbidity and mortality in pediatric patients. However, the epidemiology of pediatric brain and spine injuries in Bulgaria is poorly documented. This study aims to analyze and identify the prevalence, causes, and trends of traumatic brain and spinal cord injuries in pediatric patients during the period of 1st June 2022 to 30th June 2023. Methods A retrospective study was conducted on the medical records of patients under 18 years of age who visited the emergency department of University Multiprofile Hospital for Active Treatment (UMHAT) Burgas, Bulgaria between 1st June 2022 and 30th June 2023. The incidence and etiology were stratified by age, gender, and anamnesis. Data processing and analysis were performed with the statistical package IBM SPSS v. 26.0 (IBM Corp., Armonk, NY, USA), and graphical analysis with MS Office Excel 2016 (Microsoft, Redmond, WA, USA). Means ± standard deviation and 95% confidence interval were calculated. All p-values less than 0.05 were considered indicative of statistical significance. Results Data for patients aged <18 years, admitted to the emergency department (ED) of UMHAT Burgas, Bulgaria from 1st June 2022 to 30th June 2023 were analyzed (n=38504). Of these patients, 32% were children (n=13857). One hundred thirty-four (0.3%) of the pediatric patients were hospitalized in the neurosurgical ward, and 4653 (10.7%) were hospitalized in other wards. Of the analyzed patients, 89 are boys (66.4%), 45 are girls (33.6%) (male-female ratio 2:1) and the mean age of the patients with a head trauma was 8.07 years old. The average number of patients by diagnosis is 13.4±35.37. The largest percent are patients with brain concussion (85.07%, n=114), followed by contusion of the nerve roots in the lumbar region or late contusion wound of the head (with 2.99% each, n=4); hydrocephalus or skull fracture (with 2.24% each, n=3); contusion of the nerve roots in the thoracic region (1.49%, n=2); and fracture at Th9 vertebrae, fracture at C2 vertebrae, brain trauma or brain tumor (with 0.75% each, n=1). The average number of patients by anamnesis is 13.2±17.99. The largest percent are patients who fall from their own height (44.78%, n=60); followed by falls from height (20.90%, n=28); car accident (7.46%, n=10); injured by fight, fall from a bicycle or incident during a football game (with 5.97% each, n=8); fall from electric scooter (4.48%, n=6); hit in the closet (2.99%, n=4); and finally from bike accident or hit by a rock (with 0.75% each, n=1). From 134 hospitalized patients in neurosurgery, 114 (85.07%) did not require surgical treatment and were treated with conservative treatment and 20 (14.93%) were treated surgically.  Conclusion In conclusion, this study highlights a significant burden of pediatric traumatic brain and spinal injuries in Bulgaria. The majority of cases were managed conservatively, emphasizing the need for preventive measures.

Immunological Risk Factors in Recurrent Pregnancy Loss in Patients With Hereditary Thrombophilia.

BACKGROUND: Recurrent pregnancy loss (RPL) is a complicated reproductive disorder with underlying genetic and immunological causes. RPL may be influenced by hereditary thrombophilia, a class of blood clotting-related genetic abnormalities, via the vascular and immune systems. This study examines the immunological characteristics that hereditary thrombophilia patients have in common with RPL. METHODS: A prospective cohort study included 300 patients split into two groups: a control group without hereditary thrombophilia and a group with the condition. Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ) levels were measured, along with demographic specifics, antiphospholipid antibodies, natural killer (NK) cell counts, and other cytokines. Group differences were found using statistical analysis. RESULTS: Antiphospholipid antibodies were significantly more common in the thrombophilia group (42% testing positive, p=0.001) compared to the control group (12% testing positive), despite demographic factors being similar between groups (p=0.372 and p=0.093). When body mass index (BMI) was taken into account, the study found a statistically significant difference (p=0.046), with the thrombophilia group having a higher mean BMI (26.3 kg/m2, standard deviation (SD): 2.8) than the control group (24.7 kg/m2, SD: 3.1). IL-6 (14.8 pg/mL, SD: 3.2, p=0.029) were higher than the control group (12.4 pg/mL, SD: 2.1), and TNF-α levels were higher in the thrombophilia group (10.5 pg/mL, SD: 2.0, p=0.012) compared to the control group (8.9 pg/mL, SD: 1.5), but NK cell counts did not differ significantly (p=0.213). CONCLUSION: This study emphasizes the role of elevated pro-inflammatory cytokines (IL-6 and TNF-α) and antiphospholipid antibodies in RPL among people with hereditary thrombophilia. In this population, early detection and immunomodulatory interventions may improve pregnancy outcomes. To fully comprehend these mechanisms and create customized treatments, collaborative research is required.

Vertigo During Pregnancy: A Narrative Review of the Etiology, Pathophysiology, and Treatment.

From the time of conception until the time of labor, a woman's body and mind undergo a variety of hormonal and other changes. Patients may also experience vertigo and a lack of balance during this period. Disabling and physically painful, these symptoms may strike at any moment. Pregnancy-related vertigo has been the focus of several studies. We looked at the research on vertigo in pregnant women in detail. This narrative review aims to examine the causes, pathophysiology, and current treatments for vertigo during pregnancy. Vertigo during pregnancy has a diverse etiology, with typical causes including hormonal changes and modifications in vascular dynamics. Vertigo may start to appear due to pathophysiological mechanisms involving vestibular and central nervous system adaptations. Numerous alternatives for treatment are available, including dietary changes, vestibular therapy, medicines, and surgical procedures. The thorough assessment of the current research on vertigo during pregnancy provided by this narrative review will help medical practitioners make wise clinical decisions.

A Rare Case of Lumbar Region Diastematomyelia in a 25-year-old Woman With Lower Back Pain.

Diastematomyelia is an infrequent congenital anomaly that anatomically presents with a longitudinal division of the spinal cord at the level of one or several sections. It is generally diagnosed and treated in children. We present a 25-year-old female patient who has entered the Neurosurgery clinic after a traumatic experience with severe low back pain evaluated with 7 points on the visual analog scale (VAS). Magnetic resonance imaging (MRI) of the lumbar area discovered evidence for diastematomyelia type 1 at levels L3-L5 with deformations in L4 and L5 vertebrae and mild scoliosis. Because of the lack of neurological deficiency, the patient's treatment was conservative and included a 10-day intake of nonsteroid anti-inflammatory drugs (NSAIDs) in combination with myorelaxant and physiotherapy. On the 15th day, the patient was evaluated with 2 points on VAS. Neurological follow-up examinations were conducted on the third and the sixth month and the patient was evaluated with VAS 1, which proves that conservative treatment is successful for diastematomyelia in adults without neurological deficiency.

Navigating the Landscape of Herniated Discs: A Rare Case of Herniated Disc Regression.

A herniated disc is a condition in which the nucleus pulposus is displaced from the intervertebral space. It usually leads to back pain, thus being the most common reason for it. Patients often describe the first symptoms of a herniated disc as extreme and decisive pain. Unlike the usual mechanical back pain, a herniated disc is often related to a stinging or burning sensation that often spreads to the lower extremities and proves to be continuous at lower temperatures. We present a case of a 58-year-old male patient who visited the Acibadem City Clinic with complaints of pain initially starting from his hip, which in time extended to his left leg (L5 radiculopathy) and a few days later to his right leg (L5 radiculopathy). Before visiting the clinic, he had been treated in Germany with physiotherapy and supplements, which had proved ineffective. After an MRI, which revealed an L4-L5 herniated disc, he underwent conservative treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) and proton pump inhibitors (PPIs) for 14 days in addition to Medrol 4mg tablets (3x1 per day for 10 days). On the third day of the treatment, 60% of the symptoms had subsided. Seven months later, he came in for a scheduled checkup, and 95% of the symptoms were gone. A controlled MRI was done, and the herniated disc had completely vanished. We hope that this type of research will benefit medical professionals, patients, researchers, doctors, and students, among others. Such cases also contribute to the quality of care for such patients and help set regulated factual guidelines regarding their treatment as a whole.

Osteonecrosis of the Hip Misdiagnosed as Lumbar-Disc Herniation: Тhree Case Studies.

Disc herniation and hip-joint pathology may present with overlapping symptoms, complicating the diagnosis and treatment strategy in some cases. To ensure a correct diagnosis, this study emphasizes the need for imaging methods like MRI scans of the hip joints, complementary to the lumbar spine, when in doubt of coexisting hip pathology with symptomatic lumbar disc herniation. A typical complaint in clinical practice among patients with lumbar disc herniation is chronic back pain, often radiating down the legs. Although there could be considerable overlap in pain between hip joint issues and disc herniation, the etiology of these two conditions might differ. In these situations, a comprehensive diagnostic evaluation is crucial, as demonstrated by the three clinical case studies provided here. This article underscores the importance of conducting thorough imaging tests such as hip-joint and spine MRI scans to accurately differentiate among various disorders. Pathologies such as avascular necrosis can go unnoticed on X-rays of the hip joint, but an MRI scan provides a more precise diagnosis in these situations. The cases described here highlight the challenge of differentiating between hip-joint pathology and disc herniation due to their similar symptoms. For a diagnosis to be made quickly and accurately, modern imaging techniques must be used in conjunction with a comprehensive diagnostic approach and physical examination, which will improve patient outcomes and enable proper management.

Optimization model for production scheduling taking into account preventive maintenance in an uncertainty-based production system.

In the dynamic yet uncertain environment of Industry 4.0, industrial companies are utilizing the benefits of contemporary technologies in manufacturing by striving to implement optimization models in each stage of the decision-making process. Many organizations are focusing particularly on the optimization of two key aspects of the manufacturing process - production schedules and maintenance plans. This article presents a mathematical model with the main advantage of finding a valid production schedule (if such exists) for the distribution of individual production orders on the available production lines over a specified period. The model further considers the scheduled preventive maintenance activities on the production lines, as well as the preferences of the production planners regarding the start of the production orders and non-use of certain machines. When necessary, it also offers the possibility to make timely changes in the production schedule, and thus to handle the uncertainty as precisely as possible. For the verification of the model, two experiments were conducted (quasi-real and real-life), with data from a discrete automotive manufacturer of locking systems. The results from the sensitivity analysis demonstrated that the model further optimizes the execution times of all orders, and specifically the production lines usage - their optimal load and non-use of unnecessary machines (valid plan with 4 out of 12 lines not used). This allows for cost savings and raises the overall efficiency of the production process. Thus, the model adds value for the organization by presenting a production plan with optimal machine usage and product allocation. If incorporated into an ERP system, it could distinctly save time and streamline the production scheduling process.

Аn Unusual Case of an Epidural Lesion of the Lumbar Spine: Tumor or Hematoma?

Spinal epidural hematoma is a rare clinical entity with an incidence of approximately one per 1,000,000 patients per year. Spinal epidural hematoma is a lesion that can cause spinal cord compression or cauda equina syndrome. We report a clinical case of Ð° 69-year-old male patient who presented to the Neurosurgery Clinic of the General Hospital for Active Treatment "Dobrich" with pain and weakness in both legs for two months after falling in the bathroom. MRI revealed an L2-L3 fracture and a formation in the L2-L3 epidural space, which was compressing the nerve roots. An operative treatment was performed under general anesthesia and, intraoperatively, it was discovered that the formation was a hematoma. Aspiration of the hematoma and decompression of the spinal canal were performed. An L2-L3 stabilization with pedicle screws was done due to total laminectomy and potential instability. Postoperatively, the patient was mobilized on the day after intervention, and no surgery-related complications were observed. The patient experienced relief from his symptoms and was discharged on the fifth day. Six months post-surgery, the patient started to experience pain in his left leg. Radiography showed coxarthrosis on the left hip joint and the patient was referred to the orthopedics for further treatment.

Complex Compression Fracture in the Thoracolumbar Junction: A Case Report.

Compression fractures in the thoracolumbar junction are one of the most frequent types of spine injuries. They can be the result of trauma or underlying conditions of the vertebrae. We present a case report of a 68-year-old patient with pain and loss of mobility in the lumbar spine after sustaining a trauma via falling from a significant height. Lumbar spondylography and a following CT scan revealed a complex compression fracture of L1 with degenerative osteoporotic changes of lumbar vertebrae and several pathologies of the lumbosacral junction. A surgical intervention was performed in the form of posterior transpedicular vertebral stabilization with titanium rods and screws. Postoperatively, relief from the lumbar region pain was reported. No neurological deficit was observed. The patient was mobilized, rehabilitated, and discharged from the hospital. This case report emphasizes the use of reliable imaging methods for the diagnosis of thoracolumbar compression fracture and highlights the reliability of surgical treatment of the condition via posterior transpedicular vertebral stabilization.

Multidisciplinary Management of Invasive Basal Cell Carcinoma With Intracranial Invasion: A Rare Case Report.

The most prevalent kind of skin cancer is basal cell carcinoma (BCC). BCC invasion of the brain occurs quite rarely. Reconstruction approaches along with surgical excision are the gold standard for treating BCC. In this case, we describe a 75-year-old female patient with highly invasive BCC of the head with subdural invasion. The patient underwent surgery in 2022 in another neurosurgery clinic due to BCC of the head, frequent infection of the skin, and involvement of bone structures by the tumor. The patient presented in 2023 to the neurosurgery clinic at Saint Marina University Hospital with cephalgia, right-side hemiparesis, and a 10 x 10 cm skin defect. On a CT scan, we discovered an invasion of the parietal bones of the skull with an extension to the left subdural space. A craniectomy was performed under general anesthesia, along with hard resection to clear the margins of the BCC that had penetrated the cranial bone. Following the resection of the BCC, reconstruction of the skin defect was performed by a plastic surgeon. Consequently, a satisfactory cosmetic outcome was achieved. Postoperative complications were not observed. The patient was followed up for six months.

Review article: randomised controlled trials in inflammatory bowel disease-common challenges and potential solutions.

BACKGROUND: Recruitment rates for Crohn's disease and ulcerative colitis clinical trials continue to decrease annually. The inability to reach recruitment targets and complete trials has serious implications for stakeholders in the inflammatory bowel disease (IBD) community. Action is required to ensure patients with an unmet medical need have access to new therapies to improve the management of their IBD. AIMS: Identify challenges contributing to recruitment decline in IBD clinical trials and propose potential solutions. METHODS: PubMed and Google were used to identify literature, regulatory guidelines and conference proceedings related to IBD clinical trials and related concepts. Data on IBD clinical trials conducted between 1989 and 2020 were extracted from the Trialtrove database. RESULTS: Key aspects that may improve recruitment rates were identified. An increasingly patient-centric approach should be taken to study design including improvements to the readability of key trial documentation and inclusion of patient representatives in trial planning. Placebo is unappealing to patients; approaches including platform trials should be explored to minimise placebo exposure. Non-invasive imaging, biomarkers and novel digital endpoints should continue to be examined to reduce the burden on patients. Reducing the administrative burden associated with trials via the use of electronic signatures, for example, may benefit study sites and investigators. Changes implemented to IBD trials during the COVID-19 pandemic provided examples of how trial conduct can be rapidly and constructively adapted. CONCLUSIONS: To improve recruitment in Crohn's disease and ulcerative colitis trials, the IBD community should address a broad range of issues related to clinical trial conduct.

Serum Levels of Fibroblast Growth Factor 19 Correlate with the Severity of Diarrhea and Independently from Intestinal Inflammation in Patients with Inflammatory Bowel Disease or Microscopic Colitis.

BACKGROUND: In chronic diarrhea patients, massive over-reporting symptom-based criteria for functional bowel disorders are pitfalls. There is currently no objective biomarker that may provide a correct correlation with the severity of chronic diarrhea. To clarify the role of fibroblast growth factor-19 (FGF-19) as a biomarker of objective measurements of the severity of diarrhea in comparison with a patientreported outcome, based on the Bristol Stool Form (BSF) Scale. METHODS: Consecutive 100 patients with chronic diarrhea underwent standard investigations with laboratory tests, fecal calprotectin (FC), endoscopy with biopsies, and serum FGF-19. All patients and 14 healthy controls completed a diary recording, BSF, and stool frequency. RESULTS: We found that irritable bowel syndrome with diarrhea (IBS-D) n = 21/23 (91%) reported a high number on BSF ≥6, compared to patients with inflammatory bowel diseases (IBD) 56/77 (72%) with BSF ≥ 6 (P = .011). FGF-19 median serum levels were significantly lower in Microscopic colitis (0.010 pg/mL) and IBD patients (0.009 pg/mL) compare to IBS-D (266.9 pg/mL) and high levels in healthy subjects (463 pg/mL) (P < .001). Strong inverse correlation of FGF-19 with the stool frequency/day and stool index was found (r = -0.800, P < .001; r = -0.739, P < .001), independently from disease activity (r = -0.718, P = .001; r = -0.792, P = .001). CONCLUSION: Serum FGF-19 can become a new biomarker for evaluating the severity of diarrhea with objectively and independently from intestinal inflammation. FC and FGF-19 are predictive biomarkers for the organic cause of diarrhea.