Symptomatic Treatment Research Articles

An Outbreak of Shiga Toxin-Positive Enteroaggregative Escherichia coli O104:H4 Related Hemolytic Uremic Syndrome in Turkey: A Multicenter Study

Introduction: Serious outbreaks of Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (STEC-HUS) have been reported globally. In 2011, Germany experienced a significant outbreak of HUS caused by enteroaggregative E. coli (EAEC) O104:H4 strain. Since then, no other outbreaks of this strain have been reported. This study aims to evaluate pediatric patients affected by the second documented worldwide outbreak of STEC-HUS (EAEC O104:H4 serotype) contaminating local drinking water. Methods: Medical records of patients hospitalized in five pediatric intensive care units (PICUs) diagnosed with STEC-HUS between July and September 2022 were evaluated retrospectively. Results: Eighteen patients (14 girls and 4 boys) were enrolled in the study. The median age was 7.4 (Interquartile range [IQR] 1.3–17) years. Abdominal pain was the most common symptom (100%). The mean duration between symptom onset and development of STEC-HUS was 3 days (IQ 1–9). EAEC O104:H4 serotype was detected in the stool samples of 8 patients. Neurological involvement was observed in 3 patients, cardiac involvement in 2 patients, and both in 1 patient. Two patients required respiratory support and dialysis was performed in 16 (88.8%) patients. Plasmapheresis was administered to 2 patients, and eculizumab was given to four. No mortality was reported during follow-up; the mean durations of PICU and hospital stays were 11.3 and 31.6 days, respectively. Conclusion: Outbreaks of HUS can have serious impacts on both mortality and morbidity. However, timely diagnosis and implementation of appropriate supportive care, including dialysis, respiratory support, and medical treatment for eligible patients, can lead to favorable outcomes.

Efficacy of ensitrelvir for cough due to COVID-19 Omicron variant in medical healthcare workers.

We evaluated the efficacy of ensitrelvir for the treatment of cough due to coronavirus disease 2019 Omicron variant in medical healthcare workers. A total of 633 patients were registered in this study: 206 patients chose ensitrelvir and 427 patients chose symptomatic treatment. Difference in score changes using the Leicester Cough Questionnaire between groups was 3.17 on day 4, 3.24 on day 7, and 2.46 on day 14. The analysis demonstrated a significant difference at all time points.

Passive Anti-amyloid Beta Monoclonal Antibodies: Lessons Learned over Past 20 Years.

Alzheimer's disease (AD) is a neurodegenerative disorder that significantly impairs cognitive and functional abilities, placing a substantial burden on both patients and caregivers. Current symptomatic treatments fail to halt the progression of AD, highlighting the urgent need for more effective disease-modifying therapies (DMTs). DMTs under development are classified as either passive or active on the basis of their mechanisms of eliciting an immune response. While this review will touch on active immunotherapies, we primarily focus on anti-amyloid beta monoclonal antibodies (mAbs), a form of passive immunotherapy, discussing their multifaceted role in AD treatment and the critical factors influencing their therapeutic efficacy. With two mAbs now approved and prescribed in the clinical setting, it is crucial to reflect on the lessons learned from trials of earlier mAbs that have shaped their development and contributed to their current success. These insights can then guide the creation of even more effective mAbs, ultimately enhancing therapeutic outcomes for patients with AD while minimizing adverse events.

The effect of empagliflozin (sodium-glucose cotransporter-2 inhibitor) on osteoporosis and glycemic parameters in patients with type 2 diabetes: a quasi-experimental study.

Diabetic osteoporosis (DOP) is a metabolic disease that occurs in patients with diabetes due to insufficient insulin secretion. This condition can lead to sensory neuropathy, nephropathy, retinopathy, and hypoglycemic events, which can increase the risk of fractures. This study aimed to assess the effectiveness of Empagliflozin, a sodium-glucose cotransporter-2 (SGLT-2) inhibitor, in treating diabetic osteoporosis (DOP) and preventing fractures. This quasi-experimental study enrolled 100 patients with diabetic osteoporosis from February 2023 to February 2024. Participants were randomly assigned to an intervention group (n = 50) and a control group (n = 50). The intervention group received Empagliflozin in combination with symptomatic treatment, while the control group received only symptomatic treatment. The treatment duration was six months. Fasting blood glucose (FBG), 2-hour postprandial blood glucose (2h PG), glycosylated hemoglobin A1c (Hb A1c), bone mineral density (BMD), serum phosphorus and calcium concentration were measured after the intervention and the incidence of fracture was followed up for 12 months. The data were analyzed using SPSS 23. Descriptive statistics (mean, standard deviation, and percentage) and analytical methods (t test, Chi square) were also used to analyze the data. After six months of treatment, the intervention group exhibited significantly lower levels of FBG (P < 0.001), 2h-PG (P = 0.001), and HbA1c (P < 0.001) than the control group. Additionally, bone mineral density, serum phosphorus, and calcium levels were significantly higher in the intervention group (P < 0.001). After a 12-months follow-up, the incidence of fractures in the intervention group was 2%, while it was 16.33% in the control group (P < 0.05). Empagliflozin, when combined with symptomatic treatment, demonstrates a positive clinical effect in patients with diabetic osteoporosis. The treatment effectively improves blood glucose metabolism, bone mineral density, and phosphorus and calcium metabolism, ultimately leading to a significant reduction in the incidence of fracture.

A Review of Epithelial Ion Transporters and Their Roles in Equine Infectious Colitis.

Equine colitis is a devastating disease with a high mortality rate. Infectious pathogens associated with colitis in the adult horse include Clostridioides difficile, Clostridium perfringens, Salmonella spp., Neorickettsia risticii/findlaynesis, and equine coronavirus. Antimicrobial-associated colitis can be associated with the presence of infectious pathogens. Colitis can also be due to non-infectious causes, including non-steroidal anti-inflammatory drug administration, sand ingestion, and infiltrative bowel disease. Current treatments focus on symptomatic treatment (restoring fluid and electrolyte balance, preventing laminitis and sepsis). Intestinal epithelial ion channels are key regulators of electrolyte (especially sodium and chloride) and water movement into the lumen. Dysfunctional ion channels play a key role in the development of diarrhea. Infectious pathogens, including Salmonella spp. and C. difficile, have been shown to regulate ion channels in a variety of ways. In other species, there has been an increased interest in ion channel manipulation as an anti-diarrheal treatment. While targeting ion channels also represents a promising way to manage diarrhea associated with equine colitis, ion channels have not been well studied in the equine colon. This review provides an overview of what is known about colonic ion channels and their known or putative role in specific types of equine colitis due to various pathogens.

Directly Isolated Allogeneic Virus–Specific T Cells in Progressive Multifocal Leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML) is a life-threatening viral infection with no approved antiviral treatment. To determine whether restoring the compromised immune system of patients with PML with directly isolated allogeneic virus-specific (DIAVIS) T cells is a promising therapeutic strategy, especially if other curative options are absent. A retrospective case series of patients with PML who were treated with DIAVIS T cells was conducted between March 2020 and February 2022. T cells were isolated from healthy donors within 24 hours and targeted against the BK polyomavirus. Patients with PML were treated monocentrically. Eligibility for treatment with DIAVIS T cells was assessed for patients with confirmed PML, and exclusion criteria included stable PML disease and previous treatment with natalizumab. Fresh DIAVIS T cells were administered with a maximum dose of 2 × 104 CD3+ cells/kg body weight. Remaining T cells were cryopreserved in divided doses and administered in additional treatments approximately 2 and 6 weeks later. Primary outcome measures were clinical response and survival of patients, compared with the outcomes of a historical reference group of PML cases receiving best supportive treatment (BST) and with recently published real-world data of patients with PML who were treated with immune checkpoint inhibition. The study cohort consisted of 28 patients (median [IQR] age, 60 [51-72] years; 20 male [71.4%]). Twenty-two patients (79%) treated with DIAVIS T cells showed response, resulting in significant clinical stabilization or improvement and a reduction in viral load. Six individuals (21%) were classified as nonresponders, deteriorated rapidly, and died, as did 2 other patients during a 12-month follow-up. Older age was the only predictor of a poor treatment response. Survival analysis revealed better 12-month survival rates (hazard ratio, 0.42; 95% CI, 0.24-0.73; P =.02) from diagnosis for patients treated with DIAVIS T cells (18 of 26 [69%]; 12-mo survival rate, 69%) compared with historical controls with BST (57 of 113 [50%]; 12-mo survival rate, including censored data, 45%). This case series of DIAVIS T-cell therapy in PML provides first class IV evidence suggesting efficacy to reduce mortality and improve functional outcome. Further prospective studies are required to confirm these results.

Disorders of blood oxygenation during extracorporeal membrane oxygenation for AH1N1 pneumonia in exacerbated chronic myeloid leukemia treated by initiation of chemotherapy

Patients with severe acute respiratory distress syndrome require supportive treatment with mechanical ventilation with or without extracorporeal membrane oxygenation to maintain optimal oxygenation. Persistent inefficient blood oxygenation can be related to severity of clinical presentation, technical issues, or concomitant diseases. In this case report, man previously suffering from chronic myeloid leukemia received extracorporeal membrane oxygenation for influenza A virus subtype H1N1. Despite invasive oxygenation therapy, it was not possible to achieve amelioration of arterial blood oxygenation. After a differential diagnosis, pathological hyperleukocytosis was identified as a potential reason of oxygenation impairment, which improved after introduction of concomitant chemotherapy that lowered leukocytes count.

7815 Pembrolizumab-Induced Autoimmune Hypophysitis with “Isolated” ACTH Deficiency: Need for Heightened Awareness and Action Among Medical Fraternity

Abstract Disclosure: S. Shankar: None. S.S. Sundar: None. M.S. Vaishnav: None. L. Lekkala: None. K. Thummala: None. S. Srikanta: None. T. Deepak: None. R.B. Vijay: None. K. Muniraj: None. V. Nath: None. C. Siddlingappa: None. P. Ravikumar: None. M.D. Chitra: None. Introduction: Autoimmune hypophysitis caused by immune checkpoint inhibitors [ICIs; anti-CTLA-4 (Ipilimumab alone 7.9%), anti-PD-1 (Pembrolizumab alone 1.7%; nivolumab alone 0%)] are being increasingly documented, with anterior hypopituitarism affecting corticotrophs more commonly than thyrotrophs and gonadotrophs (large time span of onset; different recovery patterns). Clinical Case 2021 Sep Age 65 years (type 2 diabetes, hypertension). Renal Cell Carcinoma S/P radical nephrectomy. 2023 Jul PET-CT= Metastatic pleuropulmonary nodules. Four admissions to Specialist Oncology Hospital [Four 2 weekly cycles of Inj Pembrolizumab 200 mg (with Tab Axitinib 10 mg/day)]. After first cycle: progressive fatigue, body aches, drowsiness. S Sodium= Pre-pembrolizumab= 137 mEq/L (135-145); Post-pembrolizumab= 124, 134, 132, 124; T3= 1.63 to 0.60 to 1.24 to 1.35 ng/mL (0.97-1.69); T4= 6.83 to 4.93 to 10.44 to 11.44 mcg/dL (5.53-11); TSH= 10.46 to 6.28 to 5.39 to 9.48 mIU/mL (0.46-4.68); S Cortisol 8 am= 1.54 mcg/dL (5-25); S Potassium= 4.59 mEq/dL (3.5-5.1)]. One episode of loss of consciousness; EEG= abnormal; MRI Brain= normal. During every hospital admission, oncology, medical, endocrinology and nephrology teams attributed the same to “illness” (no specific diagnosis) and provided symptomatic treatment (IV 3% saline, tolvaptan and sodium bicarbonate tablets).2023 Nov Medicine: Very severe nausea, anorexia, generalised weakness, myalgia, hiccoughs, and inability to walk. Frustrated family members sought admission in “new” General Hospital. S Sodium= 119, 120; S Potassium= 4.8; S Creatinine= 1.67 mg/dL (0.7-1.3); S Uric acid= 4.5 mg/dL (4.40-7.60); Urine spot Sodium= 84 mmol/L; ESR= 144 mm. Endocrinology: S Cortisol 8 am= 0.09 mcg/dL;S Cortisol post 250 mcg Inj Synacthen= 3.76 (&amp;gt;20);Plasma ACTH= 5.4 pg/ml (9-52). S T3= 1.35; S T4= 11.44; S TSH= 9.48; LH= 3.61mIU/mL (1.5-9.3); FSH= 1.4mIU/mL (1.4-18.1); PRL= 30.1 (2.6-13.3); Testosterone total= 314 ng/dL (241-827); TPO antibodies negative. MRI-Pituitary: Partial empty sella; infundibulum neurohypophysis normal; mild asymmetric enhancement (5.5 mm) left cavernous sinus. Treatment: Tab Hydrocortisone 25 mg/day, with complete clinical and biochemical response [Suggestion of gonadotroph dysfunction and partial recovery of thyrotrope dysfunction/ injury. Hence, not on thyroxine replacement]. Clinical Lessons: Mechanisms for differential cellular vulnerability for ICI induced autoimmune pathologies [thyroid (destructive versus stimulatory), islet beta cells, adrenal cortical cells, various anterior pituitary cells (corticotrophs vs thyrotrophs and gonadotrophs] need elucidation. Specific molecular and cellular immunopathogenic pathways in different autoimmune endocrinopathies appear distinct and disparate. Presentation: 6/2/2024

Effectiveness of double-filtration plasmapheresis in reducing immunoglobulin and culprit antibody levels in neuroimmune disorders: A single-center retrospective analysis from China

ObjectiveThis study aims to evaluate the effectiveness of double-filtration plasmapheresis (DFPP) in reducing immunoglobulins and culprit antibodies in neuroimmune disorders. MethodsA retrospective analysis was conducted on 51 patients with neuroimmune diseases treated with DFPP, immunotherapy, and symptomatic treatment. Immunoglobulin and antibody levels were measured pre- and post-treatment, along with neurological function assessments using scales like the modified Rankin Scale (mRS), Expanded Disability Status Scale (EDSS), Clinical Assessment Scale for Autoimmune Encephalitis (CASE), and Myasthenia Gravis-specific scales. ResultsThe cohort included patients with neuromyelitis optica spectrum disorder (NMOSD), autoimmune encephalitis (AIE), myasthenia gravis (MG), anti-myelin oligodendrocyte glycoprotein associated disease (MOGAD), and paraneoplastic neurological syndromes (PNS). DFPP significantly reduced immunoglobulin levels (IgG, IgA, IgM) by ∼70 %. Most patients showed decreased antibody titers and significant neurological improvement. The median mRS score improved from 2 (IQR 2–3) to 1 (IQR 1–2) post-treatment, with further improvement at 90 days. Notable improvements were observed across various scales specific to NMOSD, MOGAD, AIE, and MG. Minor adverse events were reported, with no serious adverse events. ConclusionsDFPP is effective in reducing immunoglobulin and antibody levels, leading to improved neurological function in neuroimmune disorders. Further large-scale studies are warranted to confirm these findings.

Recurrent, multisystem angioedema induced by 5-azacitidine.

5-azacitidine is a hypomethylating agent (HMA) used for treating myelodysplastic syndrome (MDS) and certain myeloproliferative neoplasms (MPNs). Common side effects include myelosuppression, nausea and injection site reactions. Serious allergic reactions are rare with this class of agents. We describe a 71-year-old man with MDS/MPN who developed repeated episodes of angioedema after starting treatment with subcutaneous 5-azacitidine. Angioedema involved multiple body areas including the neck, genitalia, lower back and gastrointestinal system. Causality assessment linked this entity to 5-azacitidine via the Naranjo nomogram questionnaire, by scoring 9. 5-azacitidine was discontinued due to recurrent episodes of angioedema that occurred even after dose reduction. Steroids were helpful in terms of reversing this reaction. Afterwards, no further episodes of angioedema have been documented. The patient's thrombocytosis is currently well-controlled with low dose hydroxyurea. We report herein a unique case of recurrent, multisystem angioedema likely related to 5-azacitidine. The exact mechanism of azacitidine-induced angioedema is not currently known. Symptoms, clinical findings and timing of presentation are not always clear-cut, and it may take more than one cycle of 5-azacitidine before the diagnosis is made. Supportive and symptomatic treatment will be provided based on the severity of the reaction. Future studies may offer more insights into the mechanism underlying this rare and serious, yet intriguing side effect.

A systematic review of case reports on mortality, modes of infection, diagnostic tests, and treatments for Nipah virus infection.

First identified in Malaysia in 1998, the Nipah virus is a paramyxovirus related to the Hendra virus. The clinical manifestation can vary from a silent infection to a life-threatening encephalitis. The World Health Organization (WHO) has documented 25 outbreaks in South Asia, resulting in 429 cases and 307 deaths to date. Currently, there are no approved treatments for the deadly Nipah virus infection, which is a serious threat to public health worldwide. Consequently, a review was conducted to examine the geographic distribution of the Nipah virus, mortality, transmission pathways, and available methods for diagnosis and treatment. PubMed, Scopus, Web of Science, and Google Scholar servers were used to conduct a systematic search in compliance with the PRISMA guidelines. The results were tabulated and analyzed. A total of 12 studies (7 case series and 5 case reports) were included in the final analysis, and 92 cases were analyzed. The most frequent symptoms were fever (80%), myalgia (47%), headache (47%), shortness of breath/acute respiratory distress syndrome (n = 44.1%), altered sensorium (44.1%), and vomiting (42.6%). The most commonly used diagnostic test was RT-PCR (45.5%). The most common route of transmission reported is direct human contact with the infected patients. Treatment modalities include interventional procedures, antiviral drugs, and symptomatic treatment. The most common complications were seizures (39.2%) and altered sensorium (35.7%). The mortality rate was 73.9%. It is crucial to emphasize the importance of early Nipah virus infection diagnosis and treatment to prevent life-threatening consequences.

Post-COVID-19 condition-Clinical phenotyping in practice

The high number and clinical heterogeneity of neurological impairments in patients with apost-COVID-19 condition (PCC) poses achallenge for outpatient care. Our aim was to evaluate the applicability of the proposed subtypes according to the guidelines "Long/Post-COVID" (30 May 2024) and their phenotyping using clinical and neuropsychological findings from our post-COVID outpatient clinic. The evaluation was based on cross-sectional neurological and psychological test examinations of the patients, which were carried out using standardized questionnaires and test batteries. In addition, adetailed anamnesis of the current symptoms and aretrospective survey of the acute symptoms up to 4 weeks after the confirmed infection was conducted. The subtypes were classified according to the abovementioned guidelines based on the medical history and selected patient questionnaires, to which we added a5th subtype with reference to the previous guidelines "Long/Post-COVID" (as of 5 March 2023). Atotal of 157 patients were included between August 2020 and March 2022. The presentation was at a median of 9.4months (interquartile range, IQR = 5.3) after infection, with amean age of 49.9 years (IQR = 17.2) and more women (68%) presenting, with atotal hospitalization rate of 26%. Subtype1 (postintensive care syndrome) showed the highest proportion of men, highest body mass index (BMI) scores and the highest rates of subjective complaints of word-finding difficulties (70%). Subtype2 (secondary diseases) was dominated by cognitive impairment and had the highest depression scores. Subtype3 (fatigue and exercise-induced insufficiency) was the most common, had the most symptoms and most severe subjective fatigue and the largest proportion of women. Subtype4 (exacerbation) mainly showed affective symptoms. Subtype5 (complaints without relevance to everyday life) had the lowest scores for depression, fatigue and BMI. Neurological and psychological conditions were frequently pre-existing in all groups. The management of PCC can be improved at various levels. Astandardized subtype classification enables early individually tailored treatment concepts. Patients at risk should be identified at the primary care level and informed about risk factors and prevention strategies. Regular monitoring of cardiovascular risk factors and physical activity are essential for PCC treatment. In the case of cognitive deficits and concurrent affective symptoms, psychotherapeutic support and drug treatment with selective serotonin reuptake inhibitors (SSRI) should be provided at an early stage.

8. Herpes zoster and post herpetic neuralgia.

Patients suffering from postherpetic neuralgia (PHN) report unilateral chronic pain in one or more dermatomes after an acute herpes zoster (HZ) infection. The incidence of acute HZ ranges between three and five patients per 1000 person-years. In one out of four patients, acute HZ-related pain will transition into PHN. PHN can be very disabling for patients and reduce quality of life. Additionally, the treatment of PHN is characterized by high failure rates. The aim of this review is to give an update on the previous practical guideline published in 2011 and revised in 2015 (published in 2019) and to provide an overview of current interventional treatment options for HZ infection and PHN. The literature on the diagnosis and treatment of HZ and PHN was systematically reviewed and summarized. The most important treatment for acute HZ-related pain is antiviral therapy within 72 h of symptom onset. Additional symptomatic treatment options are analgesic drugs according to the WHO pain ladder, tricyclic antidepressants (eg, nortriptyline), and antiepileptic drugs (eg, gabapentin). If pain is not sufficiently reduced, interventional treatment such as an epidural injection with local anesthetics and corticosteroids or pulsed radiofrequency of the dorsal root ganglion (DRG) are options. Treatment for PHN is preferably transdermal capsaicin, lidocaine, or oral drugs such as antidepressants or antiepileptics. Treatment of acute HZ-related pain especially PHN is challenging. Besides the conventional treatment for PHN, interventional management is considered a new treatment option. PRF of DRG seems to be the most promising interventional management.

Orexin Receptor Antagonists for the Prevention and Treatment of Alzheimer's Disease and Associated Sleep Disorders.

Orexins/hypocretins are neuropeptides produced by the hypothalamic neurons, binding two G-protein coupled receptors (orexin 1 and orexin 2 receptors) and playing a critical role in regulating arousal, wakefulness, and various physiological functions. Given the high prevalence of sleep disturbances in Alzheimer's disease (AD) and their reported involvement in AD pathophysiology, the orexin system is hypothesized to contribute to the disease pathogenesis. Specifically, recent evidence suggests that orexin's influence may extend beyond sleep regulation, potentially affecting amyloid-β and tau pathologies. Dual orexin receptor antagonists (DORAs), namely suvorexant, lemborexant, and daridorexant, demonstrated efficacy in treating chronic insomnia disorder across diverse clinical populations. Considering their stabilizing effects on sleep parameters and emerging evidence of a possible neuroprotective role, these agents represent a promising strategy for AD management. This leading article reviews the potential use of orexin receptor antagonists in AD, particularly focusing on their effect in modulating disease-associated sleep disturbances and clinical outcomes. Overall, clinical studies support the use of DORAs to enhance sleep quality in patients with AD with comorbid sleep and circadian sleep-wake rhythm disorders. Preliminary results also suggest that these compounds might influence AD pathology, potentially affecting disease progression. Conversely, research on selective orexin receptor antagonists in AD is currently limited. Further investigation is needed to explore orexin antagonism not only as a symptomatic treatment for sleep disturbances, but also for its broader implications in modifying AD neurodegeneration, emphasizing mechanisms of action and long-term outcomes.

Infectious endocarditis complicated with intracranial infected aneurysm rupture and sinus of valsalva aneurysm rupture

BackgroundInfectious endocarditis (IE) is an infectious disease caused by direct invasion of the heart valve, endocardium, or adjacent large artery endocardium by pathogenic microorganisms. Despite its relatively low incidence, it has a poor prognosis and a high mortality. Intracranial infectious aneurysms (IIA) and ruptured sinus of Valsalva aneurysm (RSVA) are rare complications of IE.Case presentationWe report a young male patient with symptoms of respiratory tract infection, heart murmurs and other symptoms and signs. The patient also had kidney function impairment and poor response to symptomatic therapy. Blood culture was negative, but echocardiography was positive, which met the diagnostic criteria for infective endocarditis. Moreover, an echocardiography showed a ruptured sinus of Valsalva aneurysm with a ventricular septal defect. Finally, secondary rupture of an IIA with multiple organ damage led to a poor clinical outcome.ConclusionTherefore, in the clinical setting, for young patients with unexplained fever, chest pain, or palpitations, we need to be highly vigilant, considering the possibility of infective endocarditis and promptly performing blood culture, echocardiography, cerebrovascular imaging and so on, in order to facilitate early proper diagnosis and treatment.

Associations of arterial oxygen partial pressure with all‑cause mortality in critically ill ischemic stroke patients: a retrospective cohort study from MIMIC IV 2.2

BackgroundAs a supportive treatment, the effectiveness of oxygen therapy in ischemic stroke (IS) patients remains unclear. This study aimed to evaluate the relationships between arterial partial pressure of oxygen (PaO2) and both consciousness at discharge and all-cause mortality risk in ICU IS patients.MethodsBlood gas measurements for all patients diagnosed with IS were extracted from the MIMIC-IV database. Patients were classified into four groups based on their average PaO2 during the first ICU day: hypoxemia (PaO2 < 80 mmHg), normoxemia (PaO2 80–120 mmHg), mild hyperoxemia (PaO2 121–199 mmHg), and moderate/severe hyperoxemia (PaO2 ≥ 200 mmHg). The primary endpoint was 90-day all-cause mortality. Secondary outcomes included the level of consciousness at discharge, assessed by the Glasgow Coma Scale (GCS), and 30-day all-cause mortality. Multivariate Cox regression and Restricted cubic spline (RCS) analysis were used to investigate the relationship between mean PaO2 and mortality, and to assess the nonlinear association between exposure and outcomes.ResultsThis study included a total of 946 IS patients. The cumulative incidence of 30-day and 90-day all-cause mortality increased with decreasing PaO2 levels. RCS analysis revealed a nonlinear relationship between PaO2 and the risk of 30-day all-cause mortality (nonlinear P < 0.0001, overall P < 0.0001), as well as a nonlinear association between PaO2 and 90-day all-cause mortality (nonlinear P < 0.0001, overall P < 0.0001). The results remained consistent after excluding the small subset of patients who received reperfusion therapy. Sensitivity analysis indicated that the favorable impact on survival tends to increase with the extended duration of elevated PaO2.ConclusionsFor IS patients who do not receive reperfusion therapy or whose recanalization status is unknown, a lower PaO2 early during ICU admission is considered an independent risk factor for short-term and recent mortality. Adjusting respiratory parameters to maintain supraphysiological levels of PaO2 appears to be beneficial for survival, although this finding requires further validation through additional studies.Trial registrationNot applicable.

Perry Disease: Current Outlook and Advances in Drug Discovery Approach to Symptomatic Treatment.

Perry disease (PeD) is a rare, neurodegenerative, genetic disorder inherited in an autosomal dominant manner. The disease manifests as parkinsonism, with psychiatric symptoms on top, such as depression or sleep disorders, accompanied by unexpected weight loss, central hypoventilation, and aggregation of DNA-binding protein (TDP-43) in the brain. Due to the genetic cause, no causal treatment for PeD is currently available. The only way to improve the quality of life of patients is through symptomatic therapy. This work aims to review the latest data on potential PeD treatment, specifically from the medicinal chemistry and computer-aided drug design (CADD) points of view. We select proteins that might represent therapeutic targets for symptomatic treatment of the disease: monoamine oxidase B (MAO-B), serotonin transporter (SERT), dopamine D2 (D2R), and serotonin 5-HT1A (5-HT1AR) receptors. We report on compounds that may be potential hits to develop symptomatic therapies for PeD and related neurodegenerative diseases and relieve its symptoms. We use Phase pharmacophore modeling software (version 2023.08) implemented in Schrödinger Maestro as a ligand selection tool. For each of the chosen targets, based on the resolved protein-ligand structures deposited in the Protein Data Bank (PDB) database, pharmacophore models are proposed. We review novel, active compounds that might serve as either hits for further optimization or candidates for further phases of studies, leading to potential use in the treatment of PeD.

Pityriasis rosea

Pityriasis rosea is a benign self-limiting rash, usually lasting 6 to 8 weeks. In classic pityriasis rosea a ‘herald patch’ is the initial finding, a large oval patch usually found on the torso. Smaller, scaly oval pink eruptions follow after 1 to 2 weeks on the chest, back and limbs, and can resemble a Christmas tree pattern on the back. It is seen more commonly in women, with a higher incidence in pregnancy, and has an estimated prevalence of around 1.3%. The rash usually heals without scarring and often no treatment is required. Symptomatic treatment is used occasionally to alleviate pruritus. This article will explore different presentations of pityriasis rosea, how to make a diagnosis and the main management options.

Therapeutic Potential of Pomegranate Extract for Women's Reproductive Health and Breast Cancer.

Pomegranate extract has potential benefits for women's reproductive health, including fertility enhancement, menstrual cycle regulation, pregnancy support, and polycystic ovary syndrome (PCOS) treatment. It possesses antioxidant properties, reducing oxidative stress and improving fertility. Pomegranate extract may help regulate hormonal imbalances and promote regular menstrual cycles. The extract's rich nutrient profile supports placental development and fetal growth and may reduce the risk of preterm birth. Additionally, pomegranate extract shows promise in improving insulin sensitivity and reducing inflammation and oxidative damage in PCOS. Some studies suggest its potential anticancer properties, particularly against breast cancer. However, further research, including human clinical trials, is necessary to establish its effectiveness and safety. The current evidence is limited and primarily based on in vitro studies, animal studies, and clinical trials. This review provides a comprehensive summary of the benefits of pomegranate extract for women's reproductive health and breast cancer, serving as a reference for future research.

Complement-mediated hemolytic uremic syndrome associated with postpartum hemorrhage: case series and systematic review of individual participant data

BackgroundPostpartum hemorrhage is considered a risk factor for pregnancy-associated complement-mediated hemolytic uremic syndrome (CM-HUS; previously known as atypical hemolytic uremic syndrome) but has not been systematically studied. MethodsA systematic review of individual participant data from case series and reports in addition to a case series from our institution. Search terms were “thrombotic microangiopathy,” “atypical hemolytic uremic syndrome,” and “complement mediated” combined with “pregnancy,” “postpartum,” and/or postpartum hemorrhage. Cases of thrombotic microangiopathy other than CM-HUS were excluded. Outcomes were clinical and laboratory characteristics of postpartum hemorrhage-associated CM-HUS, treatment, and outcomes. ResultsThirty-three studies including 48 women with postpartum hemorrhage-associated CM-HUS and 3 patients from our institution were included in the study. Most women presented at term (28/45; 62%), delivered by cesarean section (21/41; 51%), and had pregnancy complications, mainly preeclampsia (16/51; 31%) or fetal demise (/51; 18%). Hematological and renal abnormalities usually appeared within the first 24 hours postdelivery. The median platelet count was 46 × 109/L (IQR, 45), and the median maximal lactate dehydrogenase was 2638 U/L (IQR, 1866). Renal function normalized in 20/23 (87%) women treated with C5 inhibitors with or without plasma exchange; in 7/11 (63%) women treated with plasma exchange alone, but only in 3/17 (18%) patients treated with supportive care. Patients treated with C5 inhibitors and/or plasma exchange achieved significantly better renal outcomes compared with supportive care alone (P < .001). ConclusionCM-HUS is a rare complication following postpartum hemorrhage and occurs mainly in women with preeclampsia and/or following cesarean section. Patients treated with C5 inhibitors and/or plasma exchange had a better renal prognosis compared with patients who received supportive treatment alone.