Low-dose methotrexate toxicity leading to pancytopenia: leucovorin as a rescue treatment.

Low-dose methotrexate has several known side effects associated with mild toxicity including nausea, oral ulcers, and anemia. However, it is rare for patients taking low-dose methotrexate to present with symptoms of severe toxicity including pancytopenia, macular punctate rash, and severe stomatitis. Here we present an 83-year-old patient with a history of rheumatoid arthritis on low-dose methotrexate for 1 year presenting with 5 days of worsening facial swelling, oral lesions, and a macular rash to the extremities. Initial workup revealed severe leukopenia, thrombocytopenia, and previously undiagnosed chronic kidney injury. Computed tomography showed edema surrounding a left maxillary dental implant suggestive of infection. The patient was admitted for suspected methotrexate toxicity complicated by possible dental infection. Methotrexate was withheld. The patient's stomatitis and facial swelling improved with administration of folate, leucovorin, and piperacillin/tazobactam. The patient's severe neutropenia gradually resolved following administration of granulocyte colony-stimulating factor. Infectious workup was negative throughout admission. This case report details factors that precipitate severe methotrexate toxicity at low doses.

Survival and treatment in older patients with ewing sarcoma: an analysis of the national cancer database.

BACKGROUND: Ewing sarcoma (EWS) is a malignancy which primarily arises in adolescence and has been studied extensively in this population. Much less is known about the rare patient cohort over the age of 40 at diagnosis. In this study, we describe the survival outcomes and clinical characteristics of this population. METHODS: This retrospective cohort study utilized the National Cancer Database (NCDB) to identify 4600 patients diagnosed between 2004 through 2019. Of these patients, 4058 were under the age of 40 and 542 were over 40. Propensity score 1:1 matching was performed according to sex and race. Univariate and multivariate logistic regression was performed to generate odds ratios (OR) and a Multivariate Cox regression model was used to generate a hazard ratio (HR) for patients over 40. Kaplan-Meier curves were used to estimate survival from diagnosis to death between age groups. Chi-square tests were used to compare demographic and socioeconomic patient characteristics. IBM statistics version 27.0 was used. p < 0.05 was used to indicate statistical significance. RESULTS: EWS patients older than 40 experienced worse survival outcomes compared to patients under the age of 40. 5-year survival was 44.6% for older patients vs. 61.8% for younger patients (p < 0.05). A multivariate Cox proportional hazards model showed that age was independently associated with inferior survival. (HR 1.96; p < 0.05). EWS patients over the age of 40 were more likely to have tumors originating from the vertebral column (16.1% vs 8.9%; p < 0.05) and cranium (5.3% vs. 2.9%; p < 0.05) and had a higher rate of axial tumors (31.6% vs. 18.5%; p < 0.05) compared to patients under 40. Additionally, patients older than 40 experienced a significantly longer delay between the date of diagnosis and initiation of systemic treatment (36.7 days vs. 24.8 days; p < 0.05) and were less likely to receive adjuvant chemotherapy (93.4% vs. 97.9%; p < 0.05). CONCLUSION: An age over 40 is associated with decreased survival for patients with EWS. Due to the rarity of EWS in this cohort, the optimal role of systemic treatment remains unknown and has yet to be clearly elucidated. Consequently, our findings suggest that older patients receive disparities in treatment which may be contributing to decreased survival rates.

Classic IgA-Vasculitis With Nephrotic Range Proteinuria - Rare Presentation in an Adult.

IgA vasculitis formerly known as Henoch-Schonlein Purpura is characterized by leukocytoclastic vasculitis and IgA immune complex in small vessels of the affected organ. IgA vasculitis can involve any organ system depending upon the deposition of the IgA immune complex. IgA vasculitis is a clinical diagnosis which manifest with abdominal pain, arthralgia/arthritis, palpable purpura, and kidney involvement. Occasionally, serum IgA levels or skin or kidney biopsy can help in confirming the diagnosis. Treatment is usually supportive, but studies have proved that prednisone or immunosuppressive agents can help in the prevention or progression of the disease. Hereby we present a case of 54-year-old Caucasian male who developed classic tetrad findings of IgA vasculitis most likely after receiving monkeypox vaccine which patient received three weeks prior to presentation to the hospital. Kidney involvement was present but surprisingly proteinuria was above nephrotic range making it as a rare presentation of IgA vasculitis.

Bevacizumab combined with platinum-based chemotherapy in primary or relapsed ovarian cancer patients: Meta-analysis and literature to review.

Introduction: Earlier, patients with advanced ovarian cancer were treated with a combination of cytoreductive surgery and platinum-based chemotherapy, which had significant outcomes in the past until an increase in relapse and resistance to treatment, which led to the use or development of bevacizumab (a vascular endothelial growth factor inhibitor) in the treatment of primary or relapsed ovarian cancer. Method and Methodology: This study includes five-phase three randomized controlled clinical trials designed to study the impact of bevacizumab in combination with platinum-based chemotherapy compared with platinum-based chemotherapy alone. Results: This study demonstrated significant improvement in the progression-free span but no improvement in overall survival in the treatment group when compared with the control group. Also, adverse effects reported with combination therapy were tolerable and easily manageable by decreasing the infusion rate or by decreasing the frequency of infusion.

Safety Profile of Mutant EGFR-TK Inhibitors in Advanced Non-Small Cell Lung Cancer: A Meta-analysis.

Background: Despite the use of platinum-based chemotherapy, lung cancer continues to be the leading cause of cancer-related death in the world. To overcome the rate of lung cancer-related death, scientists discovered advanced therapies, including mutant epidermal growth factor receptor-tyrosine kinase (EGFR-TK) inhibitors. Observations: We conducted a meta-analysis to determine the safety profile of mutant EGFR-TK inhibitors in the management of advanced non-small cell lung cancer (NSCLC). Included in this study are 9 phase 3 randomized controlled trials designed to study the safety profile of mutant EGFR-TK inhibitors in patients with advanced NSCLC. The study showed that mutant EGFR-TK inhibitors have an incidence of adverse effects that is less reported when compared with platinum-based chemotherapy. Conclusions: We recommend continuing using mutant EGFR-TK inhibitors in patients with advanced NSCLC especially in patients having mutant EGFR receptors. Adverse effects caused by mutant EGFR-TK inhibitors are significant but are usually tolerable and can be avoided by reducing the dosage of it with each cycle or by skipping or delaying the dose until patient is symptomatic.

Gastrointestinal manifestations, risk factors, and management in patients with post-transplant lymphoproliferative disorder: A systematic review.

BACKGROUND: Patients with a history of solid organ transplantation (SOT) or hematopoietic stem cell transplantation (HSCT) are at an increased risk of developing post-transplant lymphoproliferative disorder (PTLD). The gastrointestinal (GI) tract is commonly affected as it has an abundance of B and T cells. AIM: To determine typical GI-manifestations, risk factors for developing PTLD, and management. METHODS: Major databases were searched until November 2021. RESULTS: Non-case report studies that described GI manifestations of PTLD, risk factors for developing PTLD, and management of PTLD were included. Nine articles written within the last 20 years were included in the review. All articles found that patients with a history of SOT, regardless of transplanted organ, have a propensity to develop GI-PTLD. CONCLUSION: GI tract manifestations may be nonspecific; therefore, consideration of risk factors is crucial for identifying GI-PTLD. Like other lymphoma variants, PTLD is very aggressive making early diagnosis key to prognosis. Initial treatment is reduction of immunosuppression which is effective in more than 50% of cases; however, additional therapy including rituximab, chemotherapy, and surgery may also be required.

Role of daratumumab in relapsed or refractory multiple myeloma patient: A meta-analysis and literature to review.

Introduction: With an increase in number of cases of relapsed or refractory multiple myeloma (RRMM), scientist have discovered various combination of medications among which one is daratumumab, Daratumumab is a mono-clonal antibody which attacks CD-38 markers present in abundance on the surface of myeloma cells and is used universally for the treatment of primary newly diagnosed multiple myeloma patients. Methods and Methodology: This meta-analysis was conducted according to Cochrane Collaboration guidelines in which initially 679 articles were evaluated for relevance on abstract level followed by full text screening of final list of 45 articles. Out of the 45 articles, only 10 articles qualified for selection criteria for eligibility. Three Phase 3 randomized control clinical trials which includes primary outcomes of progression free span and secondary outcomes including complete response, partial response or very good partial response and adverse effects reported were included in this study. Results: A total of three studies including 1533 patients (849 in Daratumumab treatment group while 684 patients in control group) were included in the study. All three of these studies were phase 3 clinical trial conducted to observe the role of daratumumab in relapsed and refractory multiple myeloma. Mean age reported was 65 years in both treatment and control groups. This study showed that daratumumab improves primary and secondary outcomes including progression free span, overall response rate, very good partial response, and complete response. However, daratumumab increases drug induced adverse effects. Conclusion: Our study confirmed that daratumumab in combination therapy improved primary and secondary outcomes when compared with platinum-based chemotherapy, but more adverse effects were reported in the combination group. So, we recommend that combination therapy should include daratumumab in treatment of relapsed and refractory multiple myeloma patients.

Subcutaneous gluteal abscess from Trichosporon asahii in an immunocompetent adult.

Fungal infections have been drastically increasing in incidence in recent years, preferentially affecting immunocompromised hosts and causing potentially fatal outcomes. One of the emerging fatal fungal pathogens is Trichosporon asahii, a non-Candida yeast that has been increasingly reported in recent years. Previous literature has described T. asahii as primarily affecting immunocompromised hosts, specifically those who are neutropenic, and causing fatal disseminated infections. Herein, we describe a case of an isolated subcutaneous abscess with T. asahii in an immunocompetent host without overlying skin manifestations or predisposing factors that resulted in complete mycotic cure when treated with voriconazole and terbinafine.

Role of steroids in critically-ill sepsis patients: a review article and literature to review.

Sepsis, a life-threatening condition, commonly affecting critically ill patients, is a major cause of death worldwide. It is thus of great importance to determine the optimum management to cure this condition. This review article summarizes the role and effects of corticosteroids in the treatment of sepsis and septic shock, and to determine its mortality benefits. We used PubMed, Google scholar, Scopus, and Embase databases for literature review, and terminologies commonly searched were 'sepsis', 'septic shock', 'therapeutic use' and 'corticosteroids'. In this review article, we reviewed a total of eight different articles being done in last 10 years, relevant to the clinical outcome and effects of corticosteroids. Among those, two demonstrated improved clinical outcomes, two showed both improved clinical outcomes and decreased mortality, three showed increased adverse effects, and the remaining one showed unequivocal results.

Hemophagocytic lymph histiocytosis (HLH): etiologies, pathogenesis, treatment, and outcomes in critically ill patients: a review article and literature to review.

Hemophagocytic lymph histiocytosis (HLH) is not an independent disease but is instead a clinical syndrome that occurs in many underlying conditions involving all age groups. HLH is the consequence of a severe, uncontrolled hyperinflammatory reaction that in most cases is triggered by an infectious agent. Acquired HLH is much more common than primary HLH syndrome but primary is more fatal, and it does have the worst prognosis with no definitive treatment available to date. This review article mentioned all the latest advancements regarding etiologies, pathogenesis, treatment, and outcomes in critically ill patients who got diagnosed with HLH syndrome in last 15 years.

Prognostic importance of deranged sodium level in critically ill patients: A systemic literature to review.

It is common upon admission or during stay at a hospital or intensive care unit (ICU) for patients to present with or acquire a serum sodium abnormality. Hyponatremia, serum sodium level less than 135 mmol/L, frequently associated with critical illnesses such as heart failure and liver cirrhosis, is an indicator of disease severity as well as a risk factor for poor prognosis. Hypernatremia, serum sodium level greater than 145 mmol/L, results due to any ailment disabling a patient's modality of thirst or the ability to relieve it once sensed. Hypernatremia has a more frequent iatrogenic component than hyponatremia. It can develop insidiously among patients through IV fluid administration of saline; both its presentation upon admission and development during stay is associated with mortality. Hyponatremia is associated with increased mortality and its treatment with morbidity as it carries a risk of overcorrection and consequently the development of central pontine myelinolysis. This review article covers the findings, and subsequent correlation between findings sought, of six articles catering to underscore the correlation between sodium disorders and prognosis of hospitalized or critically ill patients. PubMed search engine was utilized to select articles befitting the purpose of this review. Cumulatively, this review article substantiates the need to diligently evaluate and treat serum sodium disorders in hospitalized patients to achieve better prognosis.

Acute Interstitial Pancreatitis With a Normal Lipase Level in the Background of Inflammatory Bowel Disease: A Case Report.

Acute interstitial pancreatitis is usually diagnosed on the basis of clinical findings, elevated lipase level, and imaging. However, herein we present a case of a 44-year-old Caucasian male who presented with pancreatitis diagnosed on the clinical grounds in the background of inflammatory bowel disease.

Asymptomatic Bacteriuria (ASB) in diabetic patients: Treat or not to treat: A prospective, observational study conducted at a tertiary care hospital.

BACKGROUND: The term asymptomatic bacteriuria (ASB) refers to the isolation of bacteria in a urine specimen of individuals who denied symptoms of urinary tract infection. Diabetes mellitus (DM) is a disease involving multiple organ systems, hallmarked for its chronicity and thus-forth endless complications including asymptomatic bacteriuria. OBJECTIVES: This study aimed to determine the characteristics of asymptomatic bacteriuria and antibiotic susceptibility pattern amongst patients with diabetes. SETTINGS AND DESIGN: A prospective observational study was conducted at a tertiary care hospital in Karachi, Pakistan. METHODS AND MATERIAL: The study included all those patients with a diagnosis of diabetes with no signs and symptoms of urinary tract infection but showing the growth of an organism in urine culture. Pregnant females and subjects who used antibiotics in last two weeks were excluded. A total of 222 urine cultures were observed prospectively who met the inclusion criteria through non-probability consecutive sampling. RESULTS: Out of 222 urine cultures observed, mean age of subjects were 62.89 ± 13.77 out of which 76% were females, and 61% had a family history of diabetes. The most frequent organisms isolated were Escherichia. Coli (E. Coli), Enterococcus, Klebsiella, Pseudomonas, and Enterobacter species. A total of 20 subjects got dual bacterial growth in their cultures among which 17 subjects had a growth of Enterococcus with any other pathogen causing UTI. Gender, family history of diabetes, levels of HBA1c, and older age groups all were found significantly associated with ASB. CONCLUSIONS: Our study is the first to analyze and study the associated risk factors amongst ASB in DM patients, and to identify the pathogens involved along with assessing their antibiotic resistance profiles. Also, due to the increase resistance to antibiotics we would recommend to use antibiotics in ASB patients only if they have any two or more comorbidities.

Antibiotic-Resistant Pyrexia of Unknown Origin: An Unusual Presentation of Myelodysplastic Syndrome.

A 74-year-old male presented to the emergency department (ED) with complaints of high-grade fever, productive cough, and difficulty breathing for three weeks, and a significant weight loss in the past six months. Despite a detailed investigation, diagnosis could not be achieved. Multiple empiric regimens were tried but no response was observed. Bone marrow biopsy was conducted after suspicious peripheral film result, which concluded that the patient was having myelodysplastic syndrome. Although pyrexia of unknown origin has a diverse group of diseases to evaluate for, and rare entities are difficult to diagnose, meticulous evaluation may give significant evidence for targeted diagnostic workup.

Role of immature platelet fraction (IPF) in sepsis patients: A systematic review.

Sepsis is extremely common amongst critically ill patients and requires early diagnosis. Hence, identifying a biomarker that could acknowledge sepsis at its prior stage is of vital significance. Immature platelets are a percentage of circulating platelets that contain RNA and is a newer parameter that is measured using automated hematology analyzers in diagnosing sepsis. This review article discusses 10 articles that reveal the role of immature platelet fraction in predicting the onset of sepsis and its relationship with mortality in sepsis. Literature search was done using PubMed, Scopus and Google Scholar and words like platelet indices and immature platelet fraction were typed in the search bar. The aim of this review article is to present a precise form of data that talk about immature platelet fraction (IPF) and its association with the severity and mortality of sepsis. Five out of 10 articles suggest that immature platelet fraction can predict the onset of sepsis and eight out of 10 articles suggest that increased IPF values are associated with high mortality.

OCCURRENCE OF UNUSUAL HAEMOGLOBINOPATHIES IN BALOCHISTAN: HB SD AND HB SE - PRESENTATION WITH OSTEOMYELITIS.

OBJECTIVE: To describe two cases of unusual variants of sickle cell disease. CASE DESCRIPTION: We present two cases of sickle cell disease variants (haemoglobinopathies), from unrelated families, in the state of Balochistan (Pakistan). One was diagnosed with sickle cell disease in the haemoglobin electrophoresis, whereas the other was diagnosed with sickle cell SE disease. Both were diagnosed based on the presentation of osteomyelitis. COMMENTS: Haemoglobin SD disease (Hb SD) and haemoglobin SE disease (Hb SE) are rare haemoglobinopathies in the world. The lack of available literature suggests that both are variants of sickle cell disease (SCD), with heterogeneous nature. The prevalence of sickle cell disease with compound heterozygotes was found at a variable frequency in the population of the Asian Southeast. The frequency of osteomyelitis in SCD is 12 to 18%, but its occurrence among variant haemoglobinopathies is little reported. Both reported cases presented with osteomyelitis as a characteristic of the disease presentation.

Occurrence of unusual haemoglobinopathies in balochistan: hb sd and hb se - presentation with osteomyelitis / Ocorrência de hemoglobinopatias incomuns no baluchistão: hb sd e hb se - apresentação com osteomielite

ABSTRACT Objective: To describe two cases of unusual variants of sickle cell disease. Case description: We present two cases of sickle cell disease variants (haemoglobinopathies), from unrelated families, in the state of Balochistan (Pakistan). One was diagnosed with sickle cell disease in the haemoglobin electrophoresis, whereas the other was diagnosed with sickle cell SE disease. Both were diagnosed based on the presentation of osteomyelitis. Comments: Haemoglobin SD disease (Hb SD) and haemoglobin SE disease (Hb SE) are rare haemoglobinopathies in the world. The lack of available literature suggests that both are variants of sickle cell disease (SCD), with heterogeneous nature. The prevalence of sickle cell disease with compound heterozygotes was found at a variable frequency in the population of the Asian Southeast. The frequency of osteomyelitis in SCD is 12 to 18%, but its occurrence among variant haemoglobinopathies is little reported. Both reported cases presented with osteomyelitis as a characteristic of the disease presentation.

RESUMO Objetivo: Descrever dois casos de variantes raras da hemoglobinopatia falciforme. Descrição do caso: Apresentamos aqui dois casos de hemoglobinopatias variantes das células falciformes, de famílias não relacionadas, no estado do Baluchistão (Paquistão), sendo um diagnosticado como doença da hemoglobina SD na eletroforese de hemoglobina, enquanto o outro com doença da hemoglobina SE. Ambos foram diagnosticados a partir da apresentação de osteomielite. Comentários: Hemoglobina SD (Hb SD) e hemoglobina SE (Hb SE) são hemoglobinopatias raras no mundo. A escassez de literatura disponível sugere que ambas são variantes da doença falciforme (DF) com natureza heterogênea. A prevalência de hemoglobinopatia falciforme com heterozigosidade composta foi encontrada com frequência variável na população do sudeste asiático. A frequência de osteomielite na DF é de 12 a 18%, mas sua ocorrência entre as hemoglobinopatias falciformes variantes é pouco relatada. Os dois casos reportados apresentaram osteomielite como característica de apresentação da doença.

Acute Sensory-Motor Axonal Neuropathy in a 57-Year-Old Male Presenting With Paresthesia and Distal Muscle Weakness.

Guillain-Barré syndrome (GBS) is a relatively uncommon post-infectious, immune-mediated neurologic disorder with an incidence of 0.5-2/100,000. It is usually preceded by an infection that evokes an immune response that cross-reacts with peripheral nerve components via molecular mimicry. The presentation of this disorder has several forms, including acute inflammatory demyelinating polyneuropathy (AIDP), acute motor axonal neuropathy (AMAN), acute motor-sensory axonal neuropathy (AMSAN), and Miller Fisher syndrome (MFS). The case we describe is of a 57-year-old male presenting with sensory features followed by symmetrical ascending paralysis and diagnosed with ASMAN, a recently described subtype of GBS, based on neurological and laboratory findings.

Frequency of Blood Transfusion in Percutaneous Nephrolithotomy.

Introduction Percutaneous nephrolithotomy (PNL) has replaced open surgery for the treatment of kidney stones due to its less invasive nature. Bleeding still occurs due to renal vascular injuries, dependent upon the access route of the procedure. Several other factors are also related to the increased risk of bleeding. This study aims to find the association between blood transfusion and other factors such as age, gender, body mass index (BMI), size of the stone, operative time, preoperative hemoglobin (Hb) level, stone surface area, hypertension, and diabetes mellitus. Materials and methods This was a descriptive cross-sectional study conducted over a period of six months between November 2019 and April 2020 at a tertiary care hospital in Karachi, Pakistan. The sample size of 131 patients was calculated using open-source epidemiological software (Open-Epi). Inclusion criteria included patients from both genders and ages between 26 and 70 years. Patients ≤25 years, having a liver disease or bleeding disorders, or refusing to participate in the study, were excluded. Laboratory data included preoperative routine complete blood count, serum creatinine (normal 0.5-1.5 mg/dL), platelet count, bleeding and coagulation profile, and urine culture. All patients also underwent renal ultrasound scans. Treatment was postponed until a negative urine culture was obtained from patients with a positive urine culture.  Results The mean age of the patients was 42.4 ± 15.65 years. One third (29.8%) of the patients were females. The stone size was 850 ± 121.43 mm², the mean operative time of the procedure was 125.76 ± 53.4 minutes, and the mean number of cell packs transfused was 1.10 ± 0.31 units. Blood transfusion was done in 24 (18.3%) of the patients. Gender, diabetes mellitus, stone size, preoperative Hb level, and operative time were significantly related to blood transfusion.  Conclusions Increased bleeding risk while performing PNL has been associated with many factors such as operating time, the gender of the patients, and stone size. Therefore, these factors should be controlled for the procedure to decrease the risk of bleeding and the need for blood transfusion. Furthermore, the kidney vasculature should not be compromised while performing the procedure.

Correlation of Fasting Lipid Profile in Patients With Chronic Liver Disease: A Descriptive Cross-Sectional Study in Tertiary Care Hospital.

INTRODUCTION: Chronic liver disease (CLD) is a term used to describe a wide spectrum of disorders, including idiopathic, infectious, genetic, drug-induced, toxin-induced, and autoimmune disorders. The common consequence of chronic damage to the liver is cirrhosis. Cirrhotic patients are further classified by their severity based on the Child-Pugh scoring system. Currently, Child-Pugh scoring consists of ascites, hepatic encephalopathy (HE), prothrombin time, serum albumin level, and total bilirubin level. Lipid panel in CLD is a great marker in determining the severity of CLD. Method and methodology: It was a descriptive cross-sectional study conducted at a tertiary care hospital. A sample size of 122 was calculated by using a RaoSoft Digital Sample Size Calculator (RaoSoft, Inc., Seattle, WA) in which we used 5% as a margin of error, 95% as confidence interval (CI), 178 as population size, and response distribution as 50%. Non-complicated CLD patients having age in between 15 and 80 years with no cirrhotic complications including HE, spontaneous bacterial peritonitis, hepato-pumonary, or hepato-renal syndrome were included in our study; the rest of the CLD patients were excluded from our study. RESULTS: The mean age of the study population was 47.09 ± 12.30 years with more than half of the patients lying among the age group 25-50 years. The study population included 76% of males (n=93) and 24% of females (n=29), with a mean age of females higher than the males. Diabetes mellitus (58.19%) was the most frequent comorbidity associated with CLD in subjects included in our study. Parameters of lipid panel were decreased exponentially as the severity of CLD increases from Child score A to C. Total cholesterol, low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL), high-density lipoprotein (HDL), and triglyceride (TG) level decreased as the severity increases in our study. The mean model for end-stage liver disease (MELD) score increased as per hypothesized as the severity increases from Child score A to Child score C, respectively. CONCLUSION: Our study concluded that as the severity of CLD increases from Child class A to Child class C, the lipid panel profile decreases exponentially which proved the idea that had been hypothesized at the beginning of our study.