Rejected

This non-interventional post-authorisation safety study (PASS) assessed the long-term safety of everolimus in patients with tuberous sclerosis complex (TSC) who participated in the TuberOus SClerosis registry to increase disease Awareness (TOSCA) clinical study and received everolimus for the licensed indications in the European Union. The rate of adverse events (AEs), AEs that led to dose adjustments or treatment discontinuation, AEs of potential clinical interest, treatment-related AEs (TRAEs), serious AEs (SAEs), and deaths were documented. One hundred seventy-nine patients were included in the first 5 years of observation; 118 of 179 patients had an AE of any grade, with the most common AEs being stomatitis (7.8%) and headache (7.3%). AEs caused dose adjustments in 56 patients (31.3%) and treatment discontinuation in nine patients (5%). AEs appeared to be more frequent and severe in children. On Tanner staging, all patients displayed signs of age-appropriate sexual maturation. Twenty-two of 106 female (20.8%) patients had menstrual cycle disorders. The most frequent TRAEs were stomatitis (6.7%) and aphthous mouth ulcer (5.6%). SAEs were reported in 54 patients (30.2%); the most frequent SAE was pneumonia (>3% patients; grade 2, 1.1%, and grade 3, 2.8%). Three deaths were reported, all in patients who had discontinued everolimus for more than 28 days, and none were thought to be related to everolimus according to the treating physicians. The PASS sub-study reflects the safety and tolerability of everolimus in the management of TSC in real-world routine clinical practice.

Copper, as a salt, is toxic and has the potential to harm multiple organs. Copper intoxication causes intravascular haemolysis followed by liver and kidney failure that can be fatal. We present a case of chronic copper sulfate poisoning in a 66-year-old man with dysphagia to solids and liquids, anaemia, acute kidney injury, liver cytolysis and hypocalcaemia. The patient improved with supportive care, but chronic kidney disease was established. Anamnesis was crucial for the diagnosis, given the non-specific signs and symptoms. The history of chronic exposure to pest treatment with a blue dust cloud made us suspect copper sulfate poisoning.

Neuropathic itch occurs due to damage of neurons of the peripheral or central nervous system. Several entities, including metabolic, neurodegenerative, orthopedic, infectious, autoimmune, malignant, and iatrogenic conditions, may affect the somatosensory system and induce neuropathic itch. Due to the complex nature of neuropathic itch, particularly concerning its clinical presentation and possible etiological factors, diagnostic work-up of this condition is challenging. A detailed medical history, especially in regard to the itch, and a comprehensive physical examination are relevant to detect characteristic signs and symptoms of neuropathic itch and to rule out other possible causes for chronic itch. Complementary diagnostic exams, especially laboratory tests, determination of the intraepidermal nerve fiber density via a skin biopsy and radiological examinations may be indicated to confirm the diagnosis of neuropathic itch and to identify underlying etiological factors. Functional assessments such as quantitative sensory testing, nerve conduction studies, evoked potentials, or microneurography may be considered in particular cases. This review article provides a comprehensive overview of the diagnostic work-up recommended for patients with neuropathic itch.

The SARS-CoV-2 virus may affect both adults and children. Although COVID-19 has a lower prevalence in infancy and has been described as mild, the clinical characteristics may vary, and there is a possibility of complications. The objectives of this study were to describe the clinical and epidemiological aspects of confirmed COVID-19 pediatric cases in the state of Sinaloa, Mexico, during the first 3 months of the pandemic, and children admitted with COVID-19 to a secondary hospital.

Recently, the term breast implant illness has become popularized in social media to describe a constellation of symptoms which have been attributed to a patient's breast implants. These symptoms include fatigue, chest pain, hair loss, headaches, chills, photosensitivity, rash, and chronic pain amongst others. While physicians aim to treat these physical symptoms, currently the evidence supports the safety of silicone breast implants. This article entitled "Breast implant illness: a topic in review" presents an up-to-date review focusing on the safety of silicone breast implants. Patients retain the right to decide to keep or remove their breast implants and for those who choose to pursue explantation, they should be advised to seek the care of a board-certified plastic surgeon. As a scientific community is our duty to continue to conduct well-designed scientific studies to gain more insight into the safety of breast implants as it related to cancer detection, autoimmune disease, and other health concerns to improve patient safety, awareness, and education. This review article aims to delineate both the content and timing of all research and evidence as it pertains to the newly coined phrase "breast implant illness". The authors of this study support that currently there have not been any concrete or evidence-based studies which support the formation of a new syndrome "silicone implant illness".

Trigeminal neuralgia is often misdiagnosed at initial presentation due to close connotation with dental pain and is often over diagnosed for the very same reasons leading to numerous unnecessary surgical procedures such as peripheral neurectomy and alcohol injections, while the actual cause may remain elusive for decades. Evaluation of the neurosensory system may disclose the correct anatomical location of the etiology. The neurological examination may be clouded by the sensory deficits subsequent to previous peripheral surgical procedures. The corneal and blink reflexes are integral measures of the trigeminal and facial neurosensory assessment, and their abnormal function may facilitate the identification of intrinsic disease of the brain stem. These reflexes can be employed to discover pathological lesions including intracranial space-occupying trigeminal, lateral medullary, cerebral hemispheric lesions, and degenerative diseases of the central nervous system. Dental surgeons and oral and maxillofacial surgeons should consider corneal reflex in neurological assessment of patient presenting with trigeminal neuralgia-like symptoms. Failure to evaluate corneal sensitivity may lead to delayed or inaccurate diagnosis and unsuitable or redundant treatment interventions. This simple noninvasive reflex can be performed by chair-side and may provide significant information regarding the origin of facial pain and is an invaluable part of clinical methods especially in remote and peripheral healthcare center practitioners where sophisticated radiographic investigations such as computed tomography and magnetic resonance imaging may not be available.

The COVID19 pandemic has impacted the lives and health of persons worldwide and although majority of COVID19 patients present with respiratory symptoms, pain emerges as an important feature of COVID19 infection. About 15-20% of patients progress to a severe condition that requires hospitalization. Although the disease was initially reported as a respiratory syndrome, other systems such as cardiovascular, renal, and nervous systems may be affected in the acute stages, increasing the need for continuous support to treat multiple sequelae caused by the disease. Due to the severity of the disease, damages found after discharge should also be considered. Providing multidisciplinary interventions promoting physical and psychological recovery in the first stages of hospitalization can minimize these damages. Cognitive, physical and psychological dysfunction reported by COVID19 patients after discharge can have profound effects on quality of life. Pain is usually part of this dysfunction, but it is still poorly understood how it affects survivors of COVID19 infections. There is limited information about the clinical characteristics, treatment and outcome of maintenance of pain in COVID19 patients. The purpose of this narrative review is to provide an overview of the implications of COVID19 on acute and chronic pain states.

Isolated sphenoid sinus mucocoeles are rare; whereas, benign lesions usually discovered incidentally. These may present with headache, diplopia, visual loss or ocular motor nerve palsies, due to slow expansion and mass effects. Prompt endoscopic removal is the key to prevent permanent sequelae. We present the case of a 63-year femele, who presented with sudden loss of vision of the left eye, along with periorbital and retrobulbar pain for the last one month. She was found to have "no light perception" vision in the left eye and optic atrophy. Neuroimaging was performed, which revealed a sphenoid sinus mucocoele, impinging on the left optic nerve. Our ENT Department performed endoscopic sinus surgery and removed it, but her vision did not return at 6-month follow-up. Although very rare, sphenoid sinus mucocoeles should be considered in the differential diagnosis of any patient, who presents with sudden visual loss. Key Words: Sphenoid sinus, Mucocoele, Optic neuropathy, Visual loss.

Thread embedding acupuncture (TEA) has recently been used as a conservative treatment method for non-specific chronic neck pain (CNP). The objective of this study was to evaluate the effectiveness and safety of TEA compared to physical therapy (PT) for treating patients with CNP.

The incidence of mastitis is high during the postpartum stage, which causes severe pain and hinders breast feeding in humans and reduces milk production in dairy cows. Studies suggested that inflammation in multiple organs is associated with oxidative stress and nuclear factor E2-related factor 2 (Nrf2)-antioxidant response element pathway is one of the most important antioxidant pathways, but the effects of Nrf2 on antioxidation in the mammary gland during mastitis are still unclear. In this study, intramammary lipopolysaccharide (LPS) challenge was carried out in wild-type (WT) and Nrf2 knockout mice. Results showed that the expression of Nrf2 affected the expression of milk protein genes (Csn2 and Csn3). Importantly, LPS treatment increased the expression of Nrf2 and HO-1 and the content of glutathione in the mammary gland of WT mice, but not in Nrf2(-/-) mice. The expression levels of glutathione synthesis genes (GCLC, GCLM, and xCT) were lower in Nrf2(-/-) mice than in WT mice. Moreover, mitochondrial-dependent apoptotic and endoplasmic reticulum stress were significantly relieved in WT mice compared with that in Nrf2(-/-) mice. In summary, the expression of Nrf2 may play an important role in prevention of oxidative and organelle stresses during endotoxin-induced mastitis in mouse mammary gland.