Rejected

The epidemic of opioid crisis started getting recognised as a public health emergency in view of increasing opioid-related deaths occurring due to undetected respiratory depression. Prescribing opioids at discharge has become an independent risk factor for chronic opioid use, following which, prescription practices have undergone a radical change. A call to action has been voiced recently to end the opioid epidemic although with the pain practitioners still struggling to make opioids readily available. American Society of Anesthesiologist (ASA) has called for reducing patient exposure to opioids in the surgical setting. Opioid sparing strategies have emerged embracing loco-regional techniques and non-opioid based multimodal pain management whereas opioid free anesthesia is the combination of various opioid sparing strategies culminating in complete elimination of opioid usage. The movement away from opioid usage perioperatively is a massive but necessary shift in anesthesia which has rationalised perioperative opioid usage. Ideal way moving forward would be to adapt selective low opioid effective dosing which is both procedure and patient specific while reserving it as rescue analgesia, postoperatively. Many unknowns persist in the domain of immunologic effects of opioids, as complex interplay of factors gets associated during real time surgery towards outcome. At present it would be too premature to conclude upon opioid-induced immunosuppression from the existing evidence. Till evidence is established, there are no recommendations to change current clinical practice. At the same time, consideration for multimodal opioid sparing strategies should be initiated in each patient undergoing surgery.

Keratoconjunctivitis sicca ("dry eye") is a common (14%-30% of adults over age 48) though difficult to treat condition that causes both discomfort and disability with associated dryness, pain, and visual disturbances. Etiology is not clearly understood but is likely varied, with a subset of patients suffering from chronic neuropathic pain referred to as "burning eye syndrome." This review of existing literature summarizes the clinical presentation, natural history, pathophysiology, and treatment modalities of burning eye syndrome. Chronicity of burning eye syndrome is likely secondary to increased nociception from the cornea, decrease in inhibitory signals, and nerve growth factor expression alterations. Treatment centers around symptomatic alleviation and reduction of inflammation. Conservative treatments focus on well-being and perception and include exercise, acupuncture, and cognitive behavioral therapy. Topical treatment consists of the anti-adhesion T-cell antagonist lifitegrast, corticosteroids, and cyclosporine; all have moderate efficacy and good safety. Autologous serum eye drops are a second-line topical that may promote corneal and neural healing on top of symptomatic relief. When these treatments fail, patients may trial neuromodulation with transcranial magnetic stimulation. Despite general treatment safety, more research is needed to develop novel approaches to this condition, possibly focusing more directly on the neurological component.

To evaluate whether a simple health and wellness coaching (HWC) program embedded within routine clinical practice resulted in improved opioid weaning and discontinuation.

Pancreatic cancer (PC) is a fatal malignancy in the human abdominal cavity that prefers to invade the surrounding nerve/nerve plexus and even the spine, causing devastating and unbearable pain. The limitation of available in vitro models restricts revealing the molecular mechanism of pain and screening pain-relieving strategies to improve the quality of life of end-stage PC patients. Here, we report a PC nerve invasion model that merged human brain organoids (hBrO) with mouse PC organoids (mPCO). After merging hBrOs with mPCOs, we monitored the structural crosstalk, growth patterns, and mutual interaction dynamics of hBrO with mPCOs for 7 days. After 7 days, we also analyzed the pathophysiological statuses, including proliferation, apoptosis and inflammation. The results showed that mPCOs tend to approximate and intrude into the hBrOs, merge entirely into the hBrOs, and induce the retraction/shrinking of neuronal projections that protrude from the margin of the hBrOs. The approximating of mPCOs to hBrOs accelerated the proliferation of neuronal progenitor cells, intensified the apoptosis of neurons in the hBrOs, and increased the expression of inflammatory molecules in hBrOs, including NLRP3, IL-8, and IL-1β. Our system pathophysiologically replicated the nerve invasions in mouse GEMM (genetically engineered mouse model) primary and human PCs and might have the potential to be applied to reveal the molecular mechanism of nerve invasion and screen therapeutic strategies in PCs.

Our patient is a 47-year-old African American female with a past medical history of recurrent episodes of small bowel obstruction. She presented to the emergency department with symptoms of nausea, vomiting, and abdominal pain. Upon further evaluation, imaging showed obstruction at the terminal ileum. Based on the holistic clinical presentation, we initially thought that this patient was experiencing symptoms of early onset Crohn's disease. Gastroenterology evaluated the patient and was uncertain of the formal diagnosis. Colonoscopy and biopsy were not pathognomonic for Crohn's disease, suggesting that there may be a component of terminal ileitis or another inflammatory bowel disease process. This case exemplifies the degree to which these inflammatory bowel disease processes frequently overlap.

Splenic injury is a rare complication of colonoscopy, estimated to occur in 0.020 to 0.034% of procedures, with a 30-day mortality of 3.6% (1-3). Of the three major severe adverse events during colonoscopy (perforation, bleeding, and splenic injury), splenic injury has the highest mortality but is rarest (1). The spleen is attached to the colonic splenic flexure by the splenocolic ligament, suggesting that manipulation of the colon during colonoscopy may cause direct tension or impaction on the spleen and splenic hilum as the mechanism of injury (2,3). Patients typically present within 24 hours of colonoscopy with severe abdominal pain and peritonism, and may be haemodynamically unstable (2). The majority of published cases of high-grade splenic injury due to colonoscopy have been managed with splenectomy (2,3), however smaller numbers have been managed with embolization and conservative measures (3). Modern treatment options for splenic injury due to colonoscopy can be classified into con- servative, endovascular, and surgical management (3). Conservative management involves inpatient moni- toring, with analgesia, intravenous fluids, and blood transfusion (2,3). Endovascular treatment is splenic artery embolization, typically with deployment of coils into the splenic artery proximal to the splenic hilum or into a single splenic artery branch in cases with an isolated focal injury (2-4). Surgical management is principally laparotomic splenectomy (2,3). In modern treatment protocols, splenectomy is usually reserved for unstable patients who require emergent laparotomy (4). Given the similarity in mechanism between splenic injuries due to blunt trauma and those due to colonoscopy, it may be helpful to conceptualize splenic injuries due to colonoscopy according to the American Association for the Surgery of Trauma (AAST) grading system (5). After institutional ethical approval, electronic medical records over a 10-year period (2012-2022) were searched to identify all patients treated for splenic injury due to colonoscopy, with the following inclusion criteria: • Splenic laceration diagnosed on computed tomography (CT). Colonoscopy within 72 hours of CT diagnosis. • Absence of blunt external traumatic incident between colonoscopy and diagnosis. Patient demographic information, past surgical history, colonoscopy indication, splenic injury grading, treatment and outcome data were analysed. Two males and 3 females were included, with median age of 63 years (range: 40-72), and four had undergone previous abdominal surgery (Table 1) (Figure 1). AAST injury grades were II to V. One patient with an AAST II injury was treated conservatively without requiring embolization or splenectomy. Three patients with AAST III-V injuries were treated primarily with splenic artery embolization, with one patient undergoing splenectomy 2 weeks later due to increased haematoma on CT. One patient with AAST III injury was treated conservatively but then underwent splenectomy 6 days later due to clinical rebleeding. All patients in the cohort survived, and 3 of 5 achieved splenic salvage. The spleen has important immune and non-immune functions, as the main filter of blood-borne pathogens, antigens, and red blood cells and patients post- splenectomy have increased life-long risk of infection(6). Embolization preserves splenic function via collateral arterial supply and splenectomy may therefore be best reserved for patients who require emergent laparotomy or where conservative and endovascular management have failed. In the present cohort, 3 of 5 patients were able to avoid splenectomy, higher than in previous published reports (47-69% splenectomy rate) (2,3). The higher splenectomy and mortality rates in previous reports may be due to publication bias favouring severe cases. As a rare complication of colonoscopy, splenic injury requires prompt diagnosis and management to minimize mortality. All patients in the present cohort survived, 3 of 5 with splenic salvage. A treatment protocol utilizing conservative management for low-grade injuries and embolization for high-grade injuries may optimise rates of splenic salvage with long-term public health benefits. This paper has not been presented previously at a conference and is not under consideration by any other journal for publication. The authors have no conflicts of interest to declare. This research was not supported by any funding.

To determine equianalgesic potency ratios for opioids with an -evidence-based approach without the use of pre-existing potency tables.

Although headache is common in pediatrics, data for the Flemish population are missing. We explored headache-prevalence, and its association with communication-technology (CT) and physical activity (PA) in Flemish children and adolescents. A cross-sectional exploratory school-based questionnaire study was designed. Flemish boys and girls (5-18 years) completed a symptom-questionnaire. sociodemographic background, headache-prevalence, headache-characteristics, CT-use and PA characteristics (self-report). : associations between headache-characteristics, age, gender, and CT-use and PA-characteristics. Four hundred twenty-four questionnaires were analysed: 5-7-years: n = 58; 8-11-years: n = 84; 12-15-years: n = 137; 16-18-years: n = 145. Fifty-five percent suffered from headache. Prevalence increased with age. More 16-18-year girls versus boys had headache. CT-use was the main headache-provocateur. Headache prevalence was significantly higher in a frequently physical active population. Our results suggest presence of headache in Flemish children and adolescents. PA-level associates with headache prevalence. However, children and adolescents with headache did not report more CT-use compared to controls.

The present study describes the case of a 25-year-old male patient who presented to the emergency department with severe headache and vertigo lasting for 3 days. The patient did not have a recent history of trauma. He was vaccinated with a second dose of the AstraZeneca COVID-19 vaccine ~1 month prior, and he suffered from a vitamin B12 deficiency due to nitrous oxide abuse. Upon an examination of his vital signs, he was found to have a body temperature of 36.4˚C, a pulse rate of 64 beats per minute, a respiratory rate of 18 breaths per minute and a blood pressure of 119/68 mmHg. A neurological examination only revealed left homonymous upper quadrantanopia. The serum platelet count of the patient was 361×1,000/µl and he had elevated D-dimer levels (0.98 µg/ml). A provisional clinical diagnosis of acute cerebrovascular accident was made. A computed tomography scan of the head revealed an abnormal hyperattenuation in the straight sinus and bilateral transverse sinuses. A diagnosis of cerebral sinovenous thrombosis (CSVT) was made following a consultation with a neurologist. The patient was treated with enoxaparin at 6,000 IU, levetiracetam at 1,000 mg and mannitol at 100 ml via an intravenous drip. After admission, magnetic resonance venography revealed the absence of flow in the straight sinus and bilateral transverse sinuses. A thrombophilic investigation revealed a plasma homocysteine level of 59.03 µmol/l (upper normal limit, 15.39 µmol/l), a vitamin B12 level of <148 (lower normal limit, 187 pg/ml). CSVT secondary to homocystinemia was diagnosed. The treatment included anticoagulation and vitamin B12 supplementation. The patient was administered vitamin B12 at 500 mcg twice per day, pyridoxine at 50 mg per day, folic acid at 5 mg two times per day and edoxaban at 60 mg per day. After 7 days of treatment, his headache and quadrantanopia were improved, and the patient was discharged.

Retinopathy of prematurity (ROP) remains among the leading causes of childhood blindness. It affects mainly premature infants who tend to be systematically and clinically unstable and are more prone to complications and anesthesia related adverse effects when undergoing examination or treatment. A better comprehension of different analgesic and anesthetic methods used during screening and treatment may help in choosing a suitable option for ROP screening and treatment. An electronic search was done using MEDLINE, PubMed, and Embase databases. Search terms used included ROP, ROP, ROP screening, ROP treatment, analgesia, and anesthesia. All randomized clinical trials, large case series, and surveys were included in the review. Topical proparacaine is the most commonly used anesthesia during ROP screening and may significantly ease pain during ROP screening. Different comfort measures during screening may help infants recover faster but do not abolish pain. Topical tetracaine seems an effective pain-relieving option during intravitreal injections for ROP treatment. Photocoagulation of the peripheral retina under general anesthesia is considered the most common practice in the treatment of ROP. Further work is necessary to better understand the options of anesthesia methods offered for the treatment of ROP patients. This is a comprehensive review highlighting the available anesthetic methods for ROP patients to aid ophthalmologists in determining the most common and current anesthetic and analgesic practices.