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Serratia marcescens endocarditis is a rare occurrence. We describe a case of Serratia endocarditis in a patient with a prosthetic valve. The clinical course was complicated by widespread embolic phenomena causing stroke, gangrene of extremities, and septic emboli to the lungs, spleen, and eyes. She was not considered suitable for surgery due to severe consumptive coagulopathy and thrombocytopenia in the setting of widespread emboli. The patient was transitioned to do not resuscitate status and discharged to a long-term care facility with a grave prognosis explained to the family.
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Background: Peripheral intravenous catheters (PIVCs) are the most commonly used invasive medical device in health care with an overall failure rate of 35-50%. Most complications are non-infectious, but local site and bloodstream infections can also occur. Even if PIVC-related infections are rare, the total number of affected patients and the preponderance of Staphylococcus aureus as related pathogen due to the frequent use of these devices are relevant arguments to implement preventive strategies. The aim of this document is to raise awareness that infections caused by PIVCs are a relevant problem that can be reduced by practice change. Methods: A panel of experts discussed this topic based on evidence and proposed practice points by consensus. Discussion: Despite published evidence-based guidelines, current practice concerning aseptic techniques during insertion and care of PIVCs often are substandard. These devices have become commonplace and tend to be perceived as safe. An overall lack of awareness about the true risks associated with the use of PIVCs results in limited surveillance and prevention efforts. Conclusion: Successful insertion and maintenance bundles in central venous lines are a blueprint to the implementation of adapted bundle strategies in the prevention of PIVC-associated infections. There is a need for studies to specifically investigate infection prevention in PIVCs and to agree on effective and implementable bundles.
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Mucopolysaccharidosis Type IIIB (MPS IIIB) is an ultrarare, fatal pediatric disease with no approved therapy. It is caused by mutations in the gene encoding for lysosomal enzyme alpha-N-acetylglucosaminidase (NAGLU). Tralesinidase alfa (TA) is a fusion protein comprised of recombinant NAGLU and a modified human insulin-like growth factor 2 that is being developed as an enzyme replacement therapy for MPS IIIB. Since MPS IIIB is a pediatric disease the safety/toxicity, pharmacokinetics and biodistribution of TA were evaluated in juvenile non-human primates that were administered up to 5 weekly intracerebroventricular (ICV) or single intravenous (IV) infusions of TA. TA administered by ICV slow-, ICV isovolumetric bolus- or IV-infusion was well-tolerated, and no effects were observed on clinical observations, electrocardiographic or ophthalmologic parameters, or respiratory rates. The drug-related changes observed were limited to increased cell infiltrates in the CSF and along the ICV catheter track after ICV administration. These findings were not associated with functional changes and are associated with the use of ICV catheters. The CSF PK profiles were consistent across all conditions tested and TA distributed widely in the CNS after ICV administration. Anti-drug antibodies were observed but did not appear to significantly affect the exposure to TA. Correlations between TA concentrations in plasma and brain regions in direct contact with the cisterna magna suggest glymphatic drainage may be responsible for clearance of TA from the CNS. The data support the administration of TA by isovolumetric bolus ICV infusion to pediatric patients with MPS IIIB.
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Objectives: The quality of health care is individually and subjectively reflected through patients' level of satisfaction, as well as the optimality and effectiveness of the provided postoperative pain management. The provision of postanesthesia care unit (PACU) service in hospitals has led to overall positive outcomes, in addition to the enhancement of patients' satisfaction with the provided pain management service. This study assessed patients' level of satisfaction with PACU service at a university hospital and discussed different factors that might have contributed to the level of satisfaction. Methods: A prospective cross-sectional study was carried out among patients after being discharged from PACU. The study took place at King Fahad Hospital of the University in Al Khobar, KSA between November 2021 and February 2022. The data were collected using a three-section predesigned questionnaire. Results: Two hundred patients were included in this study. Nearly all patients (95.5%) were satisfied with the provided pain management service. Almost all patients (99.5%) indicated that the PACU staff was courteous and professional during the entire pain management service. More patients complained about pain before using analgesia and this difference was statistically significant (Z = 8.642; p < 0.001). The satisfaction rate was significantly higher in the older age group (>45 years) (Z = 2.114; p = 0.035), in patients with American Society of Anesthesiology (ASA) 3 physical status (H = 13.130; p = 0.001), and those with a previous surgical history (Z = 2.139; p = 0.032). Conclusion: This study concluded that the level of patients' satisfaction with PACU service was high, and established a statistically significant association with age, ASA score, and previous surgical history. Healthcare providers should consider patient education and effective communication to increase patients' satisfaction level and improve the overall quality of care.
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Objective: To describe the pain intensity among hospitalized patients with calciphylaxis, elucidate the factors associated with pain improvement, and examine the link between pain improvement and clinical outcomes. Patients and Methods: Patients were identified from the Partners Research Patient Data Registry and the Partners Calciphylaxis Registry and Biorepository (Clinicaltrials.gov ID: NCT03032835). Those with calciphylaxis requiring hospitalization for at least 14 consecutive days during the study period from May 2016 through December 2021 were included. Pain intensity was assessed using patient-reported pain scores on numerical rating scales from 0 to 10. Associations between pain improvement and clinical outcomes, including lesion improvement, amputation, and mortality, were examined using univariate and multivariate regression models. Results: Our analysis included 111 patients (age, 58±14 years; men, 40%; on maintenance dialysis, 79%). No significant improvement of pain intensity was observed over the 14 days of hospitalization (mean difference, -0.71; P=.08). However, among 49 (44.1%) patients who showed at least 1-point improvement in the pain score, there was an association with surgical debridement during hospitalization (odds ratio, 3.37; 95% CI, 1.17-9.67; P=.02). Hyperbaric oxygen therapy was associated with pain improvement (odds ratio, 5.38; 95% CI, 1.14-25.50; P=.03) in patients on maintenance dialysis. Pain improvement was associated with lower rates of subsequent amputation at 6 months of follow up (6% vs 13%; P<.05) but did not predict lesion improvement or survival. Conclusion: Pain control remains a challenge among hospitalized patients with calciphylaxis. Surgical debridement and hyperbaric oxygen therapy may improve pain intensity. Pain improvement predicted a lower risk of future amputation.
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Arterial thrombosis occurs when there is endothelial damage in the setting of hypercoagulability and arterial blood stasis. COVID-19 has been theorized to cause both endothelial damage and promote hypercoagulability by causing an imbalance of clotting factors. In many studies, there have been a large proportion of COVID-19 patients that suffered a thromboembolic event, in both the venous and arterial systems. Our patient, who did not have a significant past medical history, presented with a recurrent brachial artery occlusion despite medical and surgical management, and subsequently tested positive for COVID-19 late in his admission. In conclusion, there is high suspicion that there is a relationship between COVID-19 infection and recurrent arterial thrombosis.
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A 35-year-old man with a history of active intravenous drug use presented with infective endocarditis and tricuspid valve vegetations. He was a poor candidate for open heart surgery as a result of persistent bacteremia and comorbidities, and he underwent successful aspiration therapy with a mechanical thrombectomy device for the vegetation. (Level of Difficulty: Intermediate.).
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Background/Objective: Ectopic tumoral production of parathyroid hormone (PTH) is rare. The incidence of hyperparathyroidism and osteitis fibrosa cystica (OFC) secondary to ectopic PTH secretion has only been reported in case reports, although infrequent. Case Report: We report a case of a well-differentiated pulmonary neuroendocrine tumor (NET) producing PTH that presented with severe hypercalcemia and OFC. Surgical removal of the pulmonary tumor resulted in resolution of hypercalcemia. Immunocytochemical analysis of the tumor tissue revealed PTH-positive staining. Recovery was complicated by severe hypocalcemia due to hungry bone syndrome. Discussion: To the best of our knowledge, this is the first documented case of a pulmonary NET causing OFC via PTH. We further describe the successful identification and resection of a rare NET and restoration of calcium homeostasis with aggressive calcium and vitamin D repletion. Conclusion: Although a rare cause of severe hypercalcemia and OFC, ectopic tumoral production of PTH must be considered in the differential diagnosis. Furthermore, resection of these tumors secreting PTH can lead to a protracted and severe high risk of hungry bone syndrome, which requires aggressive treatment to maintain calcium homeostasis.
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Background: Perioperative obstetric care is vital in clinical practice to improve maternal and neonatal outcomes. The standardized practice of perioperative obstetrics care service has a great role in the reduction of both expected and unexpected adverse outcomes. So, the purpose of this study was to assess the implementation of perioperative obstetric care services based on standards of Enhanced Recovery after Cesarean Delivery and the Society of Anesthesiology and Perinatology. Method and materials: A cross-sectional study was conducted on 161 mothers with an elective cesarean delivery from August 10, 2021, to May 15, 2022. The standard of this study was taken from evidence-based practice guidelines of perioperative practice for an elective cesarean delivery. Informed consent was taken from all study participants. The data was collected through direct observation using a standard checklist changed to standardized question forms with two checking components ("Yes", and "No"), and data were entered into SPSS version 20 for analysis and interpretation. Descriptive analysis was done and the results were expressed in numbers and percentages using a table. Results: A total of 161 elective cesarean sections were involved to identify the level of perioperative care. Administration of first-generation antibiotics prophylaxis, aqueous povidone-iodine solution-based skin preparations, and preparation for immediate neonatal resuscitation were fully performed based on the standards. Conclusions: The majority of elective caesarian deliveries were carried out below the recommended level as per the checklists for perioperative practice. So, added interventions are needed to improve perioperative obstetrics care services on those standards which are not totally applied and partially performed.
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Background: Patients with a left ventricular assist device with right ventricular failure are prioritized on the heart transplant waitlist; however, their post-transplant survival is less well characterized. We aimed to determine whether pretransplant right ventricular failure affects postoperative survival in patients with a left ventricular assist device as a bridge to transplant. Methods: We performed a retrospective review of the 2005-2018 Organ Procurement and Transplantation Network/United Network for Organ Sharing registry for candidates aged 18 years or more waitlisted for first-time isolated heart transplantation after left ventricular assist device implantation. Candidates were stratified on the basis of having right ventricular failure, defined as the need for right ventricular assist device or intravenous inotropes. Baseline demographic and clinical characteristics were compared among the 3 groups, and post-transplant survival was assessed. Results: Our cohort included 5605 candidates who met inclusion criteria, including 450 patients with right ventricular failure, 344 patients with a left ventricular assist device and intravenous inotropes as a bridge to transplant, 106 patients with a left ventricular assist device and right ventricular assist device, and 5155 patients with a left ventricular assist device as a bridge to transplant without the need for right side support. Compared with patients without right ventricular failure, patients with a left ventricular assist device as a bridge to transplant with right ventricular failure were younger (median age 51 years, 55 vs 56 years, P < .001) and waited less time for organs (median 51 days, 93.5 vs 125 days, P < .001). These patients also had longer post-transplant length of stay (median 18 days, 20 vs 16 days, P < .001). Right ventricular failure was not associated with decreased post-transplant long-term survival on unadjusted Kaplan-Meier analysis (P = .18). Neither preoperative right ventricular assist device nor intravenous inotropes independently predicted worse survival on multivariate Cox proportional hazards analysis. However, pretransplant liver dysfunction (total bilirubin >2) was an independent predictor of worse survival (hazard ratio, 1.74; 95% confidence interval, 1.39-2.17; P < .001), specifically in the left ventricular assist device group and not in the left ventricular assist device + right ventricular assist device/intravenous inotropes group. Conclusions: Patients with biventricular failure are prioritized on the waiting list, because their critical pretransplant condition has limited impact on their post-transplant survival (short-term effect only); thus, surgeons should be confident to perform transplantation in these severely ill patients. Because liver dysfunction (a surrogate marker of right ventricular failure) was found to affect long-term survival in patients with a left ventricular assist device, surgeons should be encouraged to perform transplantation in these severely ill patients after a recipient's optimization by inotropes or a right ventricular assist device because even when the bilirubin level is elevated in these patients (treated with right ventricular assist device/inotropes), their long-term survival is not affected. Future studies should assess recipients' optimization before organ acceptance to improve long-term survival.
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Background: Many neurodegenerative such as Alzheimer's disease (AD) are characterized by cholinergic dysfunction and oxidative stress which is a key event in neuronal death process. Thus, anticholinesterase and anti-oxidation compounds are two promising strategies in the development of AD drugs. Beyond their culinary use, spices are today studies for health purpose. In this study, some spices consumed in Cameroon were evaluated for their anticholinesterase and neuroprotective effects. Methods: Colorimetric methods were used to determine total flavonoid and alkaloid content of a combinated extract (hydroethanolic + ethanolic extracts) of different selected spices. Aftermaths, anti-cholinesterase activity of spice extract was carried out using Ellman's method. Finally, neuroprotective effects performed on human SK-N-SH cells stressed with H2O2 by assessing neuronal survival ( resazurin assay) and neuronal death (LDH assay). Results: Flavonoid content of spices extract were ranged from 22.94 to 32.01 mg EQ/g DM and alkaloid content were ranged from 320 to 896 mg EQu/g DM. Among the spices studied, Xylopia parviflora presented the greatest acetylcholinesterase inhibition with an IC50 = 14 µg/mL. In Cell culture experiments, pre-incubation of SK-N-SH cell with the selected spices at different concentrations were improved neuronal survival and reduced the percentage of neuronal cells dead. Conclusion: The present results reveal that selected spices consumed in Cameroon have good anticholinesterase activity as well as neuroprotective effect on SK-N-SH which may provide new natural compounds that could help in the management of Alzheimer's disease.
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Hepatic encephalopathy (HE) is one of the reversible complications of chronic liver disease, associated with a higher mortality rate. In current clinical practice, treatment with rifaximin and lactulose/lactitol is the first line of treatment in HE. With the advance in pathophysiology, a new class of ammonia lowering drugs has been revealed to overcome the hurdle and disease burden. The mechanism of the novel agents differs significantly and includes the alteration in intestinal microbiota, intestinal endothelial integrity, oxidative stress, inflammatory markers, and modulation of neurotoxins. Most of the trials have reported promising results in the treatment and prevention of HE with fecal microbiota transplantation, albumin, probiotics, flumazenil, polyethylene glycol, AST-120, glycerol phenylbutyrate, nitazoxanide, branched-chain amino acid, naloxone, and acetyl-l-carnitine. However, their clinical use is limited due to the presence of major drawbacks in their study design, sample size, safety profile, bias, and heterogenicity. This study will discuss the novel therapeutic targets for HE in liver cirrhosis patients with supporting clinical trial data.
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Purpose: To describe a case of local recurrence of uveal melanoma with concomitant brain metastases after secondary enucleation. Observations: A 73 year-old patient presented with dizziness and gait instability. MRI of the orbits and brain showed an anophthalmic socket with an orbital implant and an associated optic nerve mass as well as multiple mass lesions in the brain. The patient's history was significant for secondary enucleation for uveal melanoma recurrence seven years prior to presentation. Histopathology of the enucleated eye revealed no signs of extrascleral extension or optic nerve invasion. Biopsy of the optic nerve mass confirmed recurrent uveal melanoma with somatic mutations in GNAQ (Q209L) and the telomerase (TERT) promoter (c.1-124C > T) found on targeted next-generation sequencing (NGS). The same mutations were found in the primary tumor in the patient's archived enucleation samples. Conclusions: Local recurrence of uveal melanoma can occur after enucleation and is associated with an increased risk of systemic metastases. It is important for clinicians to monitor patients for local recurrence and systemic metastases even after enucleation. Genetic biomarkers may play an important role in identifying tumors at highest risk of local recurrence and metastasis. To our knowledge, this is the first case study to describe the TERT promoter mutation c.1-124C > T in the setting of recurrent uveal melanoma.
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Bacillus cereus (B. cereus) is a known cause of a food poisoning in the general population. However, it can cause life-threatening sepsis and shock in severely immunocompromised patients with hematologic malignancies, which frequently lead to central nervous system (CNS) infections associated with high mortality and morbidity. In this case report, we describe a patient with a newly diagnosed acute myeloid leukemia that underwent induction chemotherapy and developed B. cereus infection that was associated with septic shock and brain abscesses. Definitive diagnosis of multiple brain abscesses was not manifested with routine microbiological investigation but required the use of 16S ribosomal (rRNA) gene polymerase chain reaction (PCR) sequencing of the resected brain lesion. The patient was eventually treated with 8-week course of intravenous vancomycin and high-dose ciprofloxacin which led to a full recovery. This report highlights the significant risk posed by B. cereus infection in neutropenic patients, the use of 16S rRNA PCR sequencing test for definitive diagnosis and use of combination therapy for successful treatment of B. Cereus CNS infection.
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Behcet's disease (BD) is a multisystem, autoimmune vasculitis disorder affecting small, medium, and large blood vessels, with poorly understood pathogenesis. It commonly presents with recurrent aphthous ulcers, genital ulcers, skin lesions, and bilateral uveitis. Neurological symptoms are present in less than 10% of cases and develop, on average, 5-6 years after the first non-neurological symptoms. This presentation, known as Neuro-Behcet's disease (NBD), is associated with a worse prognosis of BD. Treatment for NBD is dependent on the severity of symptoms and the presence of other systemic manifestations but often initially involves glucocorticoids and a disease-modifying agent. This case report presents a 44-year-old female patient, previously diagnosed with BD, who presented with neurological symptoms and MRI findings consistent with NBD.
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Scaffold hopping refers to computer-aided screening for active compounds with different structures against the same receptor to enrich privileged scaffolds, which is a topic of high interest in organic and medicinal chemistry. However, most approaches cannot efficiently predict the potency level of candidates after scaffold hopping. Herein, we identified potent PDE5 inhibitors with a novel scaffold via a free energy perturbation (FEP)-guided scaffold-hopping strategy, and FEP shows great advantages to precisely predict the theoretical binding potencies ΔG FEP between ligands and their target, which were more consistent with the experimental binding potencies ΔG EXP (the mean absolute deviations | Δ G FEP - Δ G EXP | < 2 kcal/mol) than those ΔG MM-PBSA or ΔG MM-GBSA predicted by the MM-PBSA or MM-GBSA method. Lead L12 had an IC50 of 8.7 nmol/L and exhibited a different binding pattern in its crystal structure with PDE5 from the famous starting drug tadalafil. Our work provides the first report via the FEP-guided scaffold hopping strategy for potent inhibitor discovery with a novel scaffold, implying that it will have a variety of future applications in rational molecular design and drug discovery.
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Ketamine induced uropathy (KIU) is a urological condition increasing in prevalence, with similar symptoms to UTI, OAB syndrome or interstitial cystitis/bladder pain syndrome. We present the case of an 18-year old male who established severe LUTS and acute kidney injury due to KIU, in a short time-span of 6 months. Since cessation of ketamine is the cornerstone of treating KIU, correct and early diagnosis is essential. Physicians should therefore consider KIU as a differential diagnosis in storage LUTS, especially in younger patients with therapy-resistant LUTS.
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Background: Transient thyrotoxicosis has been documented in the setting of hyperemesis gravidarum (HG) with elevated human chorionic gonadotropin (hCG) levels. Thyroid storm in pregnancy is rarer and typically associated with autoimmune hyperthyroidism. We described thyroid storm in a primigravid 18-year-old patient due to hCG level elevation secondary to HG, which resolved in the second trimester of pregnancy. Case Report: Our patient presented with vomiting, hyperthyroidism, and cardiac and renal dysfunction at 16 weeks' gestation. She was clinically found to have a thyroid storm, with undetectable thyroid-stimulating hormone (TSH) and a free thyroxine level of >6.99 ng/dL. The hCG level was elevated at 246 030 mIU/L (9040-56 451 mIU/L). She was treated with methimazole, saturated solution potassium iodide, and propranolol. Because thyroid autoantibodies were absent, thyroid ultrasound yielded normal results, and thyroid function testing results rapidly improved as the hCG level decreased, the medications were tapered and ultimately discontinued by day 10 of hospitalization. The thyroid function remained normal after discharge. Discussion: Because hCG and TSH have identical alfa subunits and similar beta subunits, hCG can bind to the TSH receptor and stimulate thyroxine production. The hCG level peaks at around 8-14 weeks of gestation, correlating with decreased TSH levels in this same time frame. This case emphasizes the relevant physiology and importance of timely and thorough evaluation to determine the appropriate management, prognosis, and follow-up for patients with thyroid storm in the setting of HG. Conclusion: Although transient thyrotoxicosis is documented in patients with HG, thyroid storm is rare, and our case illustrates a severe example of these comorbidities.
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Early recognition of Lyme carditis is critical to preventing unnecessary pacemaker implantation for conduction abnormalities associated with this tick-born infection. Patients who do receive a pacemaker should be considered for device extraction after the completion of their antibiotic therapy if they recover normal atrioventricular node conduction. (Level of Difficulty: Intermediate.).