Rejected

TAS0313 is a multi-epitope long peptide vaccine targeting several cancer-associated antigens highly expressed in multiple cancer types, including glioblastoma (GBM). This cohort of a Phase 2 part evaluated the efficacy and safety of TAS0313 in patients with GBM.

Most of the published data relate to classical forms of rheumatic diseases (RD) and information on rare inflammatory disorders such as Behçet's syndrome (BS) and familial Mediterranean fever (FMF) is limited. We studied the frequency of side effects and disease flares after COVID-19 vaccination with either Pfizer/BioNTech or Sinovac/CoronaVac in 256 patients with BS, 247 with FMF, and 601 with RD. Telephone interviews were conducted using a questionnaire survey in a cross-sectional design in patients with BS, FMF, and RD followed by a single university hospital. Study participants were vaccinated either with CoronaVac (BS:109, FMF: 90, and RD: 343,) or BioNTech (BS: 147, FMF: 157 and RD: 258). The majority have received double dose (BS: 94.9%, FMF 92.3% and RD: 86.2%). BioNTech ensured a significantly better efficacy than CoronaVac against COVID-19 in all patient groups (BS: 1.4% vs 10.1%; FMF: 3.2% vs 12.2%, RD:2.7% vs 6.4%). Those with at least one adverse event (AE) were significantly more frequent among those vaccinated with BioNTech than those with CoronaVac (BS: 86.4% vs 45%; FMF: 83.4% vs 53.3%; and RD: 83.3% vs 45.5%). The majority of AEs were mild to moderate and transient and this was true for either vaccine. There were also AEs that required medical attention in all study groups following CoronaVac (BS: 5.5%, FMF: 3.3%, and RD:2.9%) or BioNTech (BS: 5.4%, FMF: 1.9%, and RD: 4.7%). The main causes for medical assistance were disease flare and cardiovascular events. Patients with BS (16.0%) and FMF (17.4%) were found to flare significantly more frequently when compared to those with RD (6.0%) (p < 0.001). This was true for either vaccine. BS patients reported mainly skin-mucosa lesions; there were however, 11 (4.3%) who developed major organ attack such as uveitis, thrombosis or stroke. Flare in FMF patients were associated mainly with acute serositis with or without fever. Arthralgia/arthritis or inflammatory back pain were observed mainly in the RD group. Our study demonstrates that BS and FMF patients vaccinated with either CoronaVac or BioNTech demonstrated similar AE profile and frequency compared to RD patients. AEs that required physician consultation or hospitalization occurred in all study groups after either CoronaVac or BioNTech. Increased frequency of flares in BS and FMF compared to that seen in RD might reflect defects in innate immunity and deserves further investigation. Caution should be required when monitoring these patients after vaccination.

Older adults with severe osteoporosis are the most vulnerable group of geriatric patients. They are shown the purpose of anti-osteoporotic therapy, which should be effective and safe. Teriparatide showed a decrease in the risk of fractures, an increase in BMD. In Russia, the use of teriparatide in the geriatric population is extremely scarce.

Thunderclap headache is a medical emergency presented as the worst headache ever, is characterised by an abrupt onset and maximal intensity within seconds to minutes. However, cerebrovascular causes are among the most common causes of thunderclap headache, and other non-vascular life-threatening aetiologies should be considered in evaluating a patient. We describe a 23-year-old previously healthy Latino woman who presented to our hospital after a month of repetitive severe, abrupt-onset headaches. Her prior medical history was unremarkable. After a normal brain MRI with angio-MRI, a lumbar puncture was performed with normal opening pressure, hypoglycorrhachia, increased proteins and a leucocyte; India ink staining was positive for encapsulated yeast, cultures were positive for The patient received appropriate antifungal treatment with a good response. This case highlights the particular presentation of cryptococcal meningitis due to among immunocompetent patients.

Chronic venous disease is a persistent venous drainage alteration caused by valvular incompetence and/or outflow obstruction. Disease management includes a variety of treatments, whose evidence and clinical performance in the mid-long term are variable. The objective of this umbrella review was to summarise efficacy data for pharmacological treatments including venoactive drugs from previously published reviews that included a meta-analytic component.

(OHFV) is the agent leading to Omsk haemorrhagic fever (OHF), a viral disease currently only known in Western Siberia in Russia. The symptoms include fever, headache, nausea, muscle pain, cough and haemorrhages. The transmission cycle of OHFV is complex. Tick bites or contact with infected small mammals are the main source of infection. The Republic of Kazakhstan is adjacent to the endemic areas of OHFV in Russia and febrile diseases with haemorrhages occur throughout the country-often with unclear aetiology. In this study, we examined human cerebrospinal fluid samples of patients with suspected meningitis or meningoencephalitis with unknown origins for the presence of OHFV RNA. Further, reservoir hosts such as rodents and ticks from four Kazakhstan regions were screened for OHFV RNA to clarify if this virus could be the causative agent for many undiagnosed cases of febrile diseases in humans in Kazakhstan. Out of 130 cerebrospinal fluid samples, two patients (1.53%) originating from Almaty city were positive for OHFV RNA. Screening of tick samples revealed positive pools from different areas in the Akmola region. Of the caught rodents, 1.1% out of 621 were positive for OHFV at four trapping areas from the West Kazakhstan region. In this paper, we present a broad investigation of the spread of OHFV in Kazakhstan in human cerebrospinal fluid samples, rodents and ticks. Our study shows for the first time that OHFV can not only be found in the area of Western Siberia in Russia, but can also be detected up to 1.600 km away in the Almaty region in patients and natural foci.

Professional footballers commonly experience sports-related injury and repetitive microtrauma to the foot and ankle, placing them at risk of subsequent chronic pain and osteoarthritis (OA) of the foot and ankle. Similarly, repeated heading of the ball, head/neck injuries and concussion have been implicated in later development of neurodegenerative diseases such as dementia. A recent retrospective study found that death from neurodegenerative diseases was higher among former professional soccer players compared with age matched controls. However, well-designed lifetime studies are still needed to provide evidence regarding the prevalence of these conditions and their associated risk factors in retired professional football players compared with the general male population.

Pain management is challenging for patients with sickle cell disease (SCD) who present in vaso-occlusive crisis (VOC). Opioid therapy is highly effective, nevertheless undesirable side effects can hinder their effectiveness. Regional anesthesia with deposition of perineural anesthetic offers nociceptive blockade, local vasodilatation, and reduces the inflammatory response. Among pediatric patients, continuous peripheral nerve block (CPNB) for perioperative adjunctive analgesia is safe. Herein, we describe the trajectory of a cohort of pediatric SCD patients with opioid-refractory upper-extremity VOC following placement of CPNBs for analgesia; highlighting reduced opioid consumption, improved pain scores, and decreased length of hospitalization.

Topiramate (TPM) is widely used as monotherapy or add-on therapy in adults and children (aged 2 to 16 years) with primary generalized tonic-clonic seizures or focal-onset seizures. TPM has also expanded its treatment spectrum to other seizure types and epileptic encephalopathies. Moreover, TPM has beneficial effects in some comorbidities of epilepsy such as migraine/headache and obesity. Interestingly, it also exhibited neuroprotective effects in several preclinical studies. The most common side effects of TPM are generally mild to moderate, including somnolence, dizziness, fatigue, insomnia and weight loss, which may be reduced through starting with a low dose and slowing titration to effective dosages. The mechanisms underlying the antiepileptic effect and adverse reactions of TPM have been extensively studied in the past 14 years since the last comprehensive review of TPM. Multiple mechanisms including but not limited to: (1) blockade of voltage-gated Na channels, (2) inhibition of voltage-gated Ca channels, (3) inhibition of glutamate-mediated neurotransmission, (4) inhibition of carbonic anhydrase isoenzyme, as well as (5) enhancement of GABA-mediated neurotransmission are involved in its antiepileptic effect. In this review, we aim to summarize the mechanisms, clinical benefits and adverse reactions of TPM in epilepsy treatment, and to briefly discuss the prospects of TPM.