Complete resolution across the neodymium/samarium isotopic envelope with a liquid sampling-atmospheric pressure glow discharge - Orbitrap mass spectrometer.

RATIONALE: Nd and Sm isotope ratios play an important role in geological dating and as nuclear forensic signatures; however, the overlap of the respective 144, 148, 150 Nd/Sm isobars requires prior separations to be performed before analysis on typical MS platforms. The work presented here overcomes these isobaric interferences using ultrahigh-mass resolution to alleviate interference without prior chemical separations. METHODS: A liquid sampling-atmospheric pressure glow discharge ion source was coupled to a standard, QExactive Focus Orbitrap mass spectrometer, providing a mass resolution of ~80 k. A Spectroswiss FTMS booster X2 data acquisition package was used to collect extended transients, providing much higher mass resolution; ~230 k and ~600 k are employed here for Nd and Sm isotopes. RESULTS: While the standard Orbitrap resolution is far greater than typical "atomic" MS platforms, it was insufficient to alleviate all isobars. The use of a resolution of ~230 k resulted in baseline separation across the entire isotopic envelope for both Nd and Sm. Isotope ratios obtained from Nd:Sm mixtures using high-resolution were equivalent to those found for individual-element solutions, while isotope ratios obtained at a resolution of ~80 k (standard for the OEM data system) showed large deviations. CONCLUSIONS: Use of ultrahigh-resolution is an attractive alternative to extensive chemical separations to alleviate severe isobaric interferences. Sufficient mass resolution greatly reduces/eliminates the need for sample manipulations (separations) before analysis while reducing costs and total analysis times.

Safety and efficacy of interleukin-6-receptor inhibitors in the treatment of neuromyelitis optica spectrum disorders: a meta-analysis.

BACKGROUND: Interleukin-6-receptor inhibitors like Tocilizumab and Satralizumab are showing promising results in the treatment of Neuromyelitis Optica spectrum disorder (NMOSD). We aimed to investigate the efficacy and safety of various Interleukin-6-receptor inhibitors in the management of NMO/NMOSD. METHODS: PubMed, Embase, and The Cochrane Library were systematically searched for suitable studies. Change in Annualized Relapse Ratio (ARR), Change in Extended Disability Status Scale (EDSS) s, the proportion of relapse-free patients and proportion of patients with adverse events, including serious adverse events and mortality were the parameters considered for the meta-analysis for Tocilizumab. Mean difference (MD) with 95% CI was used to quantify the change in ARR and change in EDSS before and after treatment. A forest plot was prepared to indicate the efficacy and adverse effects outcomes. The results were compared with those of Satralizumab included in two trials. RESULTS: A total of nine studies with 202 patients were included in our study. Tocilizumab found a good proportion (76.95% CI: 0.61-0.91; p < 0.001) of relapse free patients at follow up. It also significantly reduced mean ARR (mean difference: -2.6, 95% CI: - 2.71 to - 1.68; p < 0.001) and but did not show significant difference in change in EDSS score (mean difference = - 0.79, 95% CI: - 1.89 to - 0.31; p = 0.16). Also, the toxicity profile of Tocilizumab was acceptable considering the proportions of patients with adverse events 56% (95% C.I.;0.27-0.85, I2 = 88.95%, p < 0.001), proportions of patients with serious adverse events 11% (95% C.I.; 0.05 to 0.17, I2 = 0%, p < 0.001) and zero treatment related deaths. SAkura studies for Satralizumab showed similar relapse free patients (70% to 80%) and reduction of ARR and EDSS from baseline. Some studies of Tocilizumab have shown to reduce pain and fatigue while trials of Satralizumab had non-significant findings. CONCLUSION: Interleukin-6-receptor inhibitors therapy showed a promising result with good efficacy and acceptable adverse events profile for treatment of NMOSD.

Prevalence of vancomycin-resistant enterococci in Asia-A systematic review and meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: The rise of vancomycin-resistant enterococci (VRE) has been a major health problem in most countries of the world including Asia, since its discovery. There is a paucity of data on VRE in many countries of Asia as well as limited pooled estimates. Therefore, we performed a systematic review and meta-analysis to estimate a pooled prevalence of VRE in Asia. METHODS: A literature search in electronic databases like PubMed, Embase and Google Scholar and manual searching of references and grey literature, comprising the information on the prevalence of VRE with at least two species of enterococci, conducted in different countries of Asia from January 1, 2000, to September 20, 2020, was done. The random-effect model and 95% CIs was used to calculate the pooled prevalence. Subgroup, sensitivity and meta-regression analyses were performed to address heterogeneity while Egger's test for publication bias. RESULTS AND DISCUSSIONS: We identified 39 studies, comprising a total of 11,875 enterococcal isolates. The result of the analysis showed that the pooled prevalence of VRE in Asia was 8.10% (95% CI; 7-9; I2  = 93.79%; p < 0.001). Resistance to vancomycin was greater among strains of E. faecium compared to the strains of E. faecalis (22.40% vs. 3.70%). Amongst various regions of Asia, the highest prevalence of VRE was found in the Western Asian region and the lowest in the South-east Asian region. Moreover, the rate of VRE was higher than most European countries and lower than USA. WHAT IS NEW AND CONCLUSIONS: With an upsurge of VRE in Asia in recent years, efficient infection control programmes, robust surveillance systems and adherence to antibiotic stewardship are paramount to halt the further rise of VRE.

Procyanidin B2 3,3(″)-di-O-gallate, a biologically active constituent of grape seed extract, induces apoptosis in human prostate cancer cells via targeting NF-κB, Stat3, and AP1 transcription factors.

Recently, we identified procyanidin B2 3,3(″)-di-O-gallate (B2G2) as most active constituent of grape seed extract (GSE) for efficacy against prostate cancer (PCa). Isolating large quantities of B2G2 from total GSE is labor intensive and expensive, thereby limiting both efficacy and mechanistic studies with this novel anticancer agent. Accordingly, here we synthesized gram-scale quantities of B2G2, compared it with B2G2 isolated from GSE for possible equivalent biological activity and conducted mechanistic studies. Both B2G2 preparations inhibited cell growth, decreased clonogenicity, and induced cell cycle arrest and apoptotic death, comparable to each other, in various human PCa cell lines. Mechanistic studies focusing on transcription factors involved in apoptotic and survival pathways revealed that B2G2 significantly inhibits NF-κB and activator protein1 (AP1) transcriptional activity and nuclear translocation of signal transducer and activator of transcription3 (Stat3) in PCa cell lines, irrespective of their functional androgen receptor status. B2G2 also decreased survivin expression which is regulated by NF-κB, AP1, and Stat3 and increased cleaved PARP level. In summary, we report B2G2 chemical synthesis at gram-quantity with equivalent biological efficacy against human PCa cell lines and same molecular targeting profiles at key transcription factors level. The synthetic B2G2 will stimulate more research on prostate and possibly other malignancies in preclinical models and clinical translation.

Method Validation and Measurement Uncertainty Estimation for Determination of Multiclass Pesticide Residues in Tomato by Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS).

Method validation is an essential technique for ensuring the reliability and accuracy of an analytical method. This study aimed to optimize and validate a fast, reliable, and accurate method for quantitatively determining pesticide residues of diverse chemical classes in the tomato matrix. Various method performance characteristics were tested and compared with predefined criteria. Twenty-six different pesticides of diverse chemical classes were selected based on their use in tomato cultivation and the availability of reference materials. The pesticide residues in tomato samples were extracted with the QuEChERS technique with some modifications, followed by injection into an LC-MS/MS system operating in an optimized method. The validated method demonstrated reasonable specificity, as there were no interferences from matrix components at the retention times of pesticides. The calibration curves for all pesticides exhibited excellent linearities, with correlation coefficients exceeding 0.99. No significant matrix effect was observed for all pesticides in tomatoes, as the values fell within the range of ±20%. All pesticides were quantified successfully at a concentration of 5 µg/kg except for carbaryl, with an average recovery of more than 70% and a relative standard deviation of less than 20%. Similarly, measurement uncertainties were also estimated based on the validation data, and the values were found below the default limit of 50%. Subsequently, the validated method was applied to analyze 52 locally collected tomato samples. Study findings revealed that only four of the studied pesticides were detected in these samples, and their concentrations were below the maximum residue limits (500 µg/kg each for carbendazim, imidacloprid, and metalaxyl) established for tomatoes by the Government of Nepal and the Codex Alimentarius Commission.

Cytarabine-induced peripheral neuropathy in a young patient with acute myeloid leukemia: a case report.

Introduction and importance: Cytarabine, a pyrimidine analogue, is commonly used to treat multiple haematological conditions, such as acute leukaemias and lymphomas. One of the rare and less reported complications of cytarabine is peripheral neuropathy, in which peripheral nerves are damaged, often causing weakness, numbness, and pain, usually in the hands and feet. Case presentation: The authors report the case of a 17-year-old male who developed a gradual onset of weakness and sensory loss in all four limbs during treatment with a conventional dose of cytarabine for acute myeloid leukaemia. Cytarabine was discontinued after the development of symptoms, and his motor and sensory functions gradually improved over the course of 3 months. Clinical discussion: Alongside some well-known side effects of cytarabine, including bone marrow suppression, cerebellar syndrome, and cardiotoxicity, peripheral neuropathy is one of the uncommon side effects of cytarabine. Diagnosis includes identifying and grading the severity of chemotherapy-induced peripheral neuropathy (CIPN) through clinical assessment and nerve conduction studies. Management includes withdrawing the chemotherapeutic agent and supportive treatment with drugs such as duloxetine. Recent studies also favour the use of acupuncture and sensorimotor-based exercise intervention for the management of CIPN. Methods: This case report has been prepared in line with the SCARE 2023 criteria. Conclusion: Although rare, even a conventional dosage of cytarabine can cause peripheral neuropathy, and routine neuromuscular examinations can help in the early diagnosis and intervention to limit further progression and reverse the course of the disease.

Getting the diagnostic clue, role of MRI in the diagnosis of type 1 Glutaric aciduria in resource-limited settings.

Glutaric aciduria type 1 is a rare autosomal recessive disorder caused by a deficiency of glutaryl-CoA dehydrogenase, which is the key mitochondrial enzyme involved in the final degradation of lysine, L-hydroxylysine, and L-tryptophan. It is an inherited organic acidemia characterized by macrocephaly and dystonia, which results in high morbidity and mortality. In resource-limited countries like Nepal, where enzyme assays are not available, MRI has a great role to play in supporting diagnosis in such situations. Here, we present 2 cases of glutaric aciduria type 1 in brothers from the same parent that were diagnosed by MRI, and subsequent diet modification and L-carnitine therapy led to improvement of clinical symptoms.

Overuse of tetanus toxoid vaccine: a common but under-addressed issue in Nepal.

Introduction and importance: Tetanus, though potentially fatal, is preventable with proper vaccination, but high tetanus titers from frequent or higher doses can lead to increased adverse events. In countries like Nepal, where tetanus vaccines are readily available over the counter, irrational and frequent dosing, especially in certain occupational groups, is a noted issue. Case presentation: A 28-year-old metal worker presented with a superficial cut on his forearm, managed with standard wound care, and reported a history of frequent tetanus vaccinations. Given his extensive vaccination history, a tetanus toxoid injection was deemed unnecessary, and he was educated on proper vaccination schedules and advised to seek medical attention for future injuries. Clinical discussion: Timely administration of vaccines for pre-exposure and postexposure prophylaxis is crucial for combating tetanus, with booster doses recommended every 10 years or as needed for wound management. High antibody titers from frequent tetanus vaccinations can increase the risk of adverse events, prompting guidelines to avoid administering Td more frequently than every 10 years unless necessary. Local reactions, like pain and swelling at the injection site, are common, while systemic reactions can include fever and peripheral neuropathy. Over-immunization is a concern in some regions, with frequent unnecessary booster doses potentially causing harm and highlighting the need for adherence to vaccination guidelines. Conclusion: Modifying and monitoring adult Td booster vaccination can lead to significant cost savings and fewer adverse events, requiring proper vaccination record-keeping, accurate assessment, and adherence to guidelines by healthcare workers.

Bilateral Page kidney in a postpartum female: a case report.

Page kidney results from external compression of the kidney by a subcapsular hematoma and is one of the rare but treatable causes of secondary hypertension. The majority are traumatic or iatrogenic and often unilateral. Spontaneous bilateral Page kidney is rare. Case Presentation: A 35-year P1 with gestational hypertension presented with a persistent postpartum elevation of blood pressure (BP). Imaging studies revealed bilateral renal subcapsular hematoma (left>right). She was managed with an angiotensin receptor blocker initially and ultrasound-guided percutaneous drainage of the collection for the optimal control of elevated BP. Clinical Discussion: Ultrasonography and computed tomography of the kidneys are the most frequently used for diagnosing a Page kidney. Medical management with antihypertensive and regular follow-ups form the first line of treatment in Page kidneys. Percutaneous drainage, surgical decortication, laparoscopic intervention, and nephrectomy are necessary in cases of organized late hematomas. Conclusion: Spontaneous bilateral Page kidney is a rare but potentially treatable and curable form of hypertension. Percutaneous drainage is an effective method to drain the hematoma and control elevated BP.

Obturator hernia: An uncommon cause of intestinal obstruction: A case report.

INTRODUCTION AND IMPORTANCE: An obturator hernia is a rare cause of bowel obstruction. Due to its narrow passage in the obturator canal, these are more susceptible to becoming incarcerated and subsequently strangulated. Due to its challenging detection, obturator hernia is often diagnosed late. CASE PRESENTATION: A 75-year-old thin-built female with COPD presented to the emergency room with symptoms of abdominal obstruction. Abdominal examination revealed distension, firmness, rigidity, and tenderness with no bowel sounds. An erect abdominal X-ray showed multiple air-fluid levels, indicating an acute abdomen due to intestinal obstruction. Emergency exploratory laparotomy revealed an obturator hernia with strangulated ileum and perforation, necessitating resection and double barrel ileostomy. Unfortunately, despite all medical interventions, the patient succumbed to hospital-acquired pneumonia following the surgery. DISCUSSION: Obturator hernia, known as 'the skinny old woman hernia,' is rarely externally visible or palpable, leading to frequent undiagnosed cases. It presents with bowel obstruction or perforation and carries the highest morbidity among abdominal hernias. Timely intervention is crucial to prevent complications like bowel strangulation. CONCLUSION: This case report highlights the challenges of diagnosing and managing obturator hernia, a rare condition with significant morbidity. Early detection through imaging or operative findings is crucial to prevent complications like bowel strangulation, especially in older women at higher risk.

Diffuse large B-cell lymphoma in a patient treated with azathioprine for ulcerative colitis: a case report.

Azathioprine (AZA) used as an immunomodulator agent in the management of inflammatory bowel disease (IBD) increases the risk of the development of lymphoma. Case presentation: We present a case of a 45-year-old female receiving AZA for severe ulcerative colitis for 4 years. She presented with the chief complaints of bloody stool and abdominal pain for 1 month. Through a series of investigations including colonoscopy, contrast-enhanced computed tomography scan of the abdomen and pelvis, and biopsy with immunohistochemistry; she was diagnosed to have diffuse large B-cell lymphoma of the rectum. She is currently on a chemotherapeutic regimen and is planned for surgical resection after the completion of neoadjuvant therapy. Clinical discussion: AZA is classified as a carcinogen by the International Agency for Research on Cancer. Prolonged exposure to higher doses of AZA increases the risk of developing lymphoma in IBD. Previous meta-analysis and research indicate that the risk of development of lymphoma after the use of AZA in IBD increases by about four- to six-fold, especially in older age groups. Conclusions: AZA may increase the susceptibility to developing lymphoma in IBD, but the benefit far outweighs the risk. Precautions must be taken in prescribing AZA in older individuals which mandates periodic screening.

Eculizumab for paroxysmal nocturnal haemoglobinuria: catastrophic health expenditure in Nepalese patients.

Paroxysmal nocturnal hemoglobinuria (PNH) results from a mutation in the phosphatidylinositol glycan class-A gene which causes uncontrolled complement activation with resultant intravascular hemolysis and its sequelae. Eculizumab is a terminal complement inhibitor that blocks this complement activation and has revolutionized the treatment of PNH but comes with an enormous price which can have catastrophic health expenditure in low-middle income countries (LMIC) like Nepal. Here, we discuss the potential way forwards in the treatment of PNH in Nepal and other LMICs.

Obstructed hemivagina and ipsilateral renal agenesis: magnetic resonance imaging findings in young Nepali females - a report of four cases.

Obstructed hemivagina and ipsilateral renal agenesis (OHVIRA) syndrome also known as the Herlyn-Werner-Wunderlich Syndrome is a rare embryological disorder associated with Mullerian and mesonephric duct abnormality. Case presentation: The cases presented describe the imaging (ultrasound and MRI) findings of four young females who presented with dysmenorrhea and urinary complaints. All of them had solitary kidneys with a didelphic uterus and unilateral hematometrocolpos. A proximally blind-ending ureter with distal ectopic insertion, transverse vaginal septum, and left-sided endometrioma was seen. Clinical discussion: OHVIRA syndrome is associated with duplicated uterovaginal structure with OHVIRA. Ultrasound is the first line of investigation; however, MRI better delineates the anatomy and assists in preoperative planning. Conclusion: This report highlights that earlier clinical suspicion and imaging diagnosis of OHVIRA is crucial to prevent adverse outcomes and treating complications.

High-Altitude Exposure and Cerebral Venous Thrombosis: An Updated Systematic Review.

Kharel, Sanjeev, Suraj Shrestha, Samriddha Raj Pant, Suman Acharya, Amit Sharma, Santosh Baniya, and Sanjeeb S. Bhandari. High-altitude exposure and cerebral venous thrombosis: an updated systematic review. High Alt Med Biol. 24:167-174, 2023. Background: High altitude (HA) may increase the risk of cerebral venous thrombosis (CVT). Differentiating it from other HA illnesses is crucial for prompt treatment and better outcomes. We aimed to summarize the clinical data, etiology, and risk factors of this poorly understood entity at an HA. Materials and Methods: A systematic literature search of various databases, including PubMed, Embase, and Google Scholar, was done using relevant keywords; cerebral venous thrombosis; HA, up to May 1, 2022. Results: A total of nine studies, including 75 cases of CVT at HA (3,000-8,848 m), with 66 males and 9 females, were included in this review. Headache and seizure were the most common clinical presentations. Smoking, drinking habits, and the use of oral contraceptive pills (OCP) were the most common risk factors for the development of CVT. Similarly, various underlying hypercoagulable states were also present among cases of CVT associated with HA exposure. Conclusion: Our review concludes that HA exposure can predispose individuals with risk factors such as preexisting hypercoagulable states, smoking, drinking habits, and use of OCP to an increased risk of CVT.

Chest wall mass as a sign of ignored hepatocellular carcinoma in an alcoholic cirrhotic patient: a case report.

Bone metastasis of hepatocellular carcinoma (HCC) is usually seen in the course of advanced intrahepatic HCC. Isolated bone metastasis as an initial manifestation of HCC is uncommon. Case presentation: The authors report a case of a 68-year-old male with a history of chronic alcohol consumption who presented with epigastric pain, abdominal distension, and a hard, tender lump on the right posterolateral aspect of his back. Investigation revealed HCC with isolated metastasis to the posterior thoracic wall. Clinical discussion: HCC usually develops secondary to chronic hepatitis B and C infection in the background of chronic liver disease. Common presenting symptoms of bone metastasis include local pain, neurological manifestations, palpable subcutaneous masses, and pathological fractures. An immunohistochemistry analysis is important to differentiate HCC from non-HCC metastasis in patients without known underlying HCC. Treatment is often directed towards palliative care as the prognosis is poor. Conclusion: An isolated rib mass can be an initial presentation of metastatic HCC. Thus, HCC with bone metastasis should be considered in the differential diagnosis in patients presenting with painful swelling in the thoracic region.

Imaging spectrum in rhino-orbito-cerebral mucormycosis: a cross-sectional study.

Background: Rhino-orbital-cerebral mucormycosis (ROCM) is a life-threatening condition caused by a saprophytic fungus that predominately affecting immune-compromised patients. Early diagnosis of ROCM is of utmost importance to start the treatment as early as possible to prevent early and horrible complications of the disease. Materials and methods: This retrospective study evaluated the imaging findings of 21 patients with biopsy and KOH mount-based evidence of invasive ROCM. The imaging was obtained from a Siemens Magnetom Amira 1.5T system with a strength of 1.5T or more. The spectrum of findings was evaluated for the sites of involvement, signal intensity, contrast characteristics, necrotic component as well as orbital, infratemporal, and intracranial extensions, especially cavernous sinuses, Meckel's cave, and the brain parenchyma. Results: The mean age of the patients was 55.8±10.9 years and included 71% male. All the patients were positive for COVID-19 and the majority were diabetic. MRI showed predominant involvement of the maxillary sinus (17, 81%) and the ethmoidal sinus (15, 71.4%). The orbital extension was present in 18 cases (86%). T1-weighted imaging showed iso to low signal intensity in involved sinuses in the majority of the patients (9, 42.9%). Heterogeneously high signal intensity was observed in T2-weighted and short tau inversion recovery images in all the patients. Heterogenous contrast enhancement was present in 20 (95.2%) patients. Conclusion: The imaging spectrum of ROCM is variable. Multiplanar MRI with postcontrast images is a very useful complementary tool to the clinical evaluation to assess the extent of disease and its complications, which has a high mortality. Clinicians and radiologists should be aware of the imaging spectrums of ROCM.

A Rare Coexistence of Simultaneous Cardio-Cerebral Infarction.

Background: Contemporaneous acute myocardial infarction (AMI) and acute ischemic stroke (AIS), termed cardio-cerebral infarction (CCI), is a rare medical emergency. The effectual management of this situation is exigent since early management of one condition will inevitably delay the other. Case Presentation. A 60-year-old woman presented to our hospital with concurrent AMI of the inferior left ventricular wall, complicated by cardiogenic shock and transient complete heart block, and AIS of more than 4.5 hour duration. The cerebral computerized tomography angiography revealed a right-sided terminal internal carotid artery (ICA) occlusion, and the coronary angiogram depicted double vessel disease with a culprit lesion in the right coronary artery (RCA). The patient underwent mechanical thrombectomy for the ICA occlusion by an interventional neuroradiologist followed by the primary percutaneous coronary intervention of the culprit RCA by the interventional cardiologists in the same setting. Conclusion: A patient with concurrent AMI and AIS is a challenging situation to treat in the emergency department, and the treatment must be individualized for each patient.

Organizing pneumonia as an initial presentation in a male lupus: A rare case report.

Organizing pneumonia (OP) is one of the rare pulmonary manifestations of systemic lupus erythematosus (SLE) which is infrequently reported as a presenting manifestation. Early diagnosis of lupus-related OP with the help of imaging, can drive to prompt initiation of immunosuppressive therapy leading to a better prognosis. We present a case of a 34-year-old young male who presented with fever, myalgia, and a dry cough for 1 month and was later diagnosed as SLE-related organizing pneumonia.

Fusobacterium bacteremia presenting with inferior mesenteric vein thrombosis.

Isolated mesenteric vein thrombosis associated with Fusobacterium is rare. Physicians should be aware regarding the association of Fusobacterium with thrombosis at various sites.

Breakage of an orogastric tube in a critically Ill patient: a case report.

Orogastric and nasogastric tubes are common methods of enteral feeding. Although the methods of tube feeding are simple, these methods are not free of complications. Case presentation: This case report describes a 58-year-old patient with the diagnosis of stroke, in whom there was breakage of an orogastric tube during a prolonged ICU stay. Clinical discussion: Early enteral feeding in patients without any contraindications is associated with improved organ survival and recovery, and decreased incidence of infections, which decreases the ICU stay and improves the overall outcome. Nasogastric and orogastric tubes are the most commonly inserted feeding tubes. Breakage of an orogastric tube is a rare complication that can occur due to manufacturing defects, exposure to a harsh acidic environment, and forceful flushing of an obstructed tube. Conclusions: Timely identification of the broken feeding tube can help the treating clinicians retrieve it easily even with the help of a laryngoscope in selected patients.