Rejected

The present SARS-CoV-2 induced COVID-19 pandemic is responsible for millions of deaths, illnesses, and economic loss worldwide. There are 21 COVID-19 vaccines from different platforms approved worldwide for emergency use until 13 August 2021. Later, BNT162b2 obtained full approval from the FDA. The efficacy of the leading vaccines such as BNT162b2, mRNA-1273, Gam-Covid-Vac, Ad26.COV2.S, ChAdOx1 nCoV-19, and BBIBP-CorV, against SARS-CoV-2 documented as 95%, 94.1%, 91.6%, 67%, 70.4%, and 78.1%, respectively. Moreover, against the Delta variant of SARS-CoV-2, BNT162b2, ChAdOx1 nCoV-19, and BBV152 showed 88%, 70%, and 65.2% efficacy, respectively. Apart from the common adverse effects such as fever, fatigue, headache, and pain in the injection site, Bell's palsy with BNT162b2, myocarditis and pericarditis with mRNA-1273, and thrombosis with ChAdOx1 nCoV-19 have been reported though seemed not alarming. Furthermore, global production and distribution of vaccines should be ensured in an equal and justifiable way that the immunity and protection against the virus would be optimum and persistent.

Sleep disturbances are extremely common (40-86%) in children and adolescents, especially those with autism spectrum disorders (ASD) and are often among the first symptoms identified by parents at a very early stage of their child's development. These abnormalities are among the main parental concerns when having a child with ASD and have a significant impact on the quality of life of patients, their parents, and more broadly their siblings. Sleep disorders are essentially abnormalities of the sleep-wake rhythm – primarily sleep onset insomnia or nocturnal awakenings (with difficulty falling back to sleep). These disturbances can be accompanied by other sleep disorders, requiring notably a systematic elimination of the presence of a sleep apnea or restless legs syndrome – to ensure a personalized and efficient therapeutic approach. Physiologically, the determinants of these sleep disorders are poorly understood, even though several studies point to a significant decrease in melatonin synthesis in people with ASD. Melatonin is a hormone that facilitates falling asleep and maintaining sleep and is also involved in the endogenous synchronization of internal biological clocks. However, the causal factors of this decrease in melatonin synthesis are largely unknown, involving to a small extent the genes involved in melatonin synthesis pathway. The treatment of sleep disorders is relatively systematic: after eliminating other specific sleep disorders associated with the complaint of insomnia, as well as other possible associated comorbidities (such as seizures), a global and graduated therapeutic approach must be put in place. This treatment will be non-pharmacological as a first line, then pharmacological as a second line. A number of non-pharmacological treatment strategies for sleep disorders in typically developing children and adolescents, as well as those with ASD, have been shown to be effective. This treatment requires a combination of: 1) parental education to promote sleep development; 2) setting up bedtime rituals adapted to the child's age and particularities; 3) specific behavioral strategies including bedtime fading, gradual extinction and positive reinforcement of adapted behaviors. It is very essential that the parents are accompanied throughout this therapy. Sleep hygiene and behavioral care must also take into consideration the important role of the zeitgebers of sleep-wake rhythms, i.e. the external environmental factors involved in the synchronization of the biological clocks: regular exposure to light at adapted times, regular meal and wake-up times, social activities and times for going to school. The evidence for the effectiveness of behavioral interventions in the treatment of behavioral insomnia in the typical developmental child is strong, since 94% of children show clinically significant improvements in nighttime sleepiness and waking. By contrast, only about 25% of children with ASD are improved by an approach combining sleep hygiene and behavioral therapy. Melatonin has a special and prominent place in the drug management of sleep disorders associated with ASD. Several clinical trials have shown that melatonin is effective in treating sleep disorders in patients with ASD. This work led to the European Medicines Agency (EMA) granting marketing authorization in September 2018 for a sustained-release paediatric melatonin molecule (Slenyto®). This synthetic molecule is a prolonged release melatonin (PRM) which mimics the physiological pharmacokinetic and secretory characteristics of endogenous melatonin, having a very short blood half-life and prolonged secretion for several hours during the night. A recent study evaluated the efficacy and safety of pediatric PRM (mini-tablets) in 125 children, aged 2 to 17.5 years with mainly ASD. After 15 days on placebo, the children were randomized into two parallel groups, PRM or placebo in a double-blind design for 13 weeks. At endpoint, total sleep time was increased by an average of 57.5 minutes on PRM and only 9.14 minutes on placebo (P=0.034). This difference between the two groups was already significant after three weeks of treatment (P=0.006). Sleep latency was also improved in the PRM group (-39.6 minutes) compared to placebo (-12.51 minutes) (P=0.01). Consolidated sleep duration (uninterrupted by awakenings) was improved by 77.9 minutes for the PRM group and only 25.4 minutes for the placebo group (P<0.001). PRM was well tolerated, the most frequent side effects being headache and daytime drowsiness at the same level with PRM or placebo. In addition, the acceptability by the children for swallowing the mini-tablets was excellent (100% compliance). The efficacy and tolerability of PRM was maintained over the medium and long term in the open phase, over a total study duration of 2 years.

Ineffective pain control is the most commonly cited reason for misuse of prescription opioids and is influenced by genetics. In particular, the gene encoding the CYP2D6 enzyme, which metabolizes some of the most commonly prescribed opioids (e.g., tramadol, hydrocodone) to their more potent forms, is highly polymorphic and can lead to reduced concentrations of the active metabolites and decreased opioid effectiveness. Consideration of the genotype may allow for predicting opioid response and identifying patients who are likely to respond well to lower potency opioids as well as those who may derive greater pain relief from non-opioid analgesics versus certain opioids. There is emerging evidence that a -guided approach to pain management improves pain control and reduces opioid consumption and thus may be a promising means for combating opioid misuse. Clinical practice guidelines are available for select opioids and other analgesics to support medication and dose selection based on pharmacogenetic data. This article describes the evidence supporting genotype-guided pain management as a means of improving pain control and reducing opioid misuse and clinical recommendations for genotype-guided analgesic prescribing. In addition, a "how to" guide using patient case examples is provided to demystify the process for implementing pharmacogenetics-guided pain management in order to optimize analgesia and minimize adverse effects. Optimizing pain management through genotype-guided approaches may ultimately provide safer and more effective therapy for pain control while decreasing the risk for opioid misuse.

While musculoskeletal pain is cited as the primary cause of disability and reason for visiting the emergency department in the United States, secondary etiologies should be considered. In this case report, we are reporting a unique case of a 38-year-old multiparous healthy female who presented to multiple emergency departments with fleeting pain on the shoulders and upper back. She was diagnosed with muscle spasms and joint arthritis and discharged home multiple times. The patient then developed vaginal bleeding, belt-line numbness, and was found to have T6 spinal cord compression. Imaging prompted workup for malignancy, which revealed small cell neuroendocrine cervical cancer (SCNECC) with metastasis to intra-abdominal lymph nodes, bone, and brain. SCNECC is very rare, aggressive, occurs in less than 3% of cervical cancers, and does not have established treatment guidelines. Because it is commonly misdiagnosed and has an overall poor prognosis, SCNECC can be missed if it is not part of the differential.

Osteoarthritis (OA) of the knee is the most common rheumatic disease that is characterized by degradation of articular cartilage, subchondral bone alteration, meniscal degeneration, synovial inflammatory response, and overgrowth of bone and cartilage. In severe OA, the reduced mobility caused by pain can increase bone loss and reduction of bone mineral density leading to osteoporosis.

The coronavirus disease (COVID-19 or SARS-CoV-2) pandemic has brought the global community to a halt. A return to normalcy is dependent on effective reopening strategies that encourage herd immunity through the implementation of vaccines. Cardiopulmonary inflammation has been reported in SARS-CoV-2 infection, independent of the severity, mainly amongst the juvenile population. Cardiovascular involvement following SARS-CoV-2 infection is associated with higher mortality and morbidity. Cardiovascular complications following COVID-19 vaccination have been documented as less severe, with no link between cardiovascular injury and death. This case report describes the presentation of an otherwise healthy 18-year-old male who experienced retrosternal chest pain after receiving a first dose of the mRNA-1273 vaccine. The patient had a negative polymerase chain reaction (PCR) test for COVID-19 infection. An electrocardiogram revealed diffuse ST elevation and PR segment depression, with increased inflammatory markers consistent with pericarditis. Elevation of troponin (16 ng/mL), evidence of borderline reduced ejection fraction (50-55%), and global left ventricular hypokinesis were suggestive of myopericarditis. Infectious and autoimmune studies were negative. The patient was treated mainly with non-steroidal anti-inflammatory drugs and colchicine, which resulted in a significant improvement of clinical symptoms. As the administration of emergency COVID-19 vaccines continues worldwide, it is of paramount importance to be aware of possible adverse events, including those affecting the cardiovascular system.

Patients in the intensive care unit (ICU) are often under stress and fail to cooperate well with invasive treatments. Analgesia and sedation are of great significance for reducing the suffering of patients and ensuring the application and effectiveness of treatment. For better clinical choice, we aimed to explore the effect of the combination of propofol + fentanyl or midazolam + fentanyl on the short-term prognosis of hospitalized patients in the ICU.

The objective of this case report is to highlight a rare case of infectious thoracic aortic aneurysm and purulent pericarditis simultaneously in a 56-year-old woman. The patient complained of left anterior chest pain and contrast computed tomography (CT) revealed infectious thoracic aortic aneurysm and purulent pericarditis accompanied by massive pericardial effusion. She underwent a pericardial drainage immediately, and antibiotic treatment was initiated. Methicillin-sensitive Staphylococcus aureus was detected in blood and pericardial fluid cultures. On day eight of hospitalization, contrast CT scan showed enlargement of the aortic aneurysm. Therefore, total arch replacement was performed on day 10 using rifampicin-soaked graft. After surgery, antibiotic treatment was continued, till inflammatory markers became negative. She was discharged on day 66 without developing anastomotic pseudoaneurysms nor constrictive pericarditis.

Pilonidal sinus is a chronic, inflammatory condition. Controversy exists regarding the best surgical management for pilonidal sinus, including the extent of excision and type of closure of the surgical wound.