Clinical and epidemiological features and therapeutic options of avascular necrosis in patients with sickle cell disease (SCD): a cross-sectional study.

BACKGROUND: Avascular necrosis (AVN) is a debilitating complication in sickle cell disease (SCD) patients, and its management is usually challenging. This study aims to evaluate the clinical and epidemiological features and therapeutic options of AVN in sickle cell patients in Qatar. PATIENTS AND METHODS: A cross-sectional study was conducted on a 49 SCD patients who were diagnosed with AVN and attended the hematology clinic at the National Center for Cancer care & research, Hamad Medical Corporation, Qatar between Jan-2011 to Jan2021.  Results: Forty-nine adult patients with SCD who were diagnosed with AVN were studied. The median age of the study population is 32 years, and the median age at the first AVN diagnosis was 26 years (range: 11-44 yr.). 37 (75.5%) patients suffered from multiple joints AVN while 12(24.5%) had single joint involvement. 31 (63.3%) patients had bilateral hip AVN and 18 (36.7%) had shoulder involvement. 30 patients (61%) were on Hydroxyurea treatment. Based on FICAT and Alert classification of AVN, 57 % of patients had stage III and above at first diagnosis. 20 (40.8%) were managed with a conservative approach, 11 (22.4%) received hyperbaric oxygen with good response, 6(12.2%) underwent hip core decompression and 12(24.5%) underwent hip replacement surgery. CONCLUSION: In SCD patients, AVN occurred more during the 3rd and 4th decades of life. The majority of AVN represented with advanced stage and had multiple joint involvements. We recommend adopting a low threshold of joint imaging for early detection and prevention of further complications.

Body contouring after bariatric surgeries in Jordan: Awareness, prevalence, and challenges: A multicentric cross-sectional study.

Body-contouring surgeries are known to improve the quality of life and body image of patients undergoing bariatric surgery. However, only a small number of patients choose to undergo body-contouring surgeries. This study evaluated the prevalence of body-contouring surgeries among patients who underwent bariatric surgery in Jordan, and identified the limitations encountered. This study is an observational multicentric cross-sectional study. A validated questionnaire was distributed to patients who had undergone bariatric surgeries between July 2017 and June 2021 at the University of Jordan Hospital and a bariatric surgery private center in Amman, Jordan. Inclusion criteria were based on the type of bariatric surgery (Sleeve Gastrectomy or Roux-En-Y gastric bypass) and the surgery date falling within the study period, with participation requiring the completion of an online questionnaire. Collected data was analyzed using various statistical tests, with a predetermined alpha level of 0.05 to determine statistical significance. Of 451 eligible participants, a total of 305 patients completed the validated questionnaire. Of these, 11 responses were excluded due to incomplete data. The analysis focused on remaining 294 participants who underwent bariatric surgery between July 2017 and June 2021, with only 7 participants (2.4%) electing to undergo body-contouring surgeries. The primary barriers to body-contouring surgeries reported by participants were cost (62.7%) and fear of postoperative complications (31.8%). Females exhibited a significantly greater desire for body-contouring surgeries (P = .000), which was also related to the percentage of total weight loss following bariatric surgery (P = .025). However, no significant associations were observed between desiring body-contouring surgeries and marital status (P = .734) or employment status (P = .319). The low rate of body-contouring surgeries in Jordan reflects the importance of strengthening the patient-physician relationship through targeted education efforts that emphasize the expected consequences of bariatric surgery and the available solutions to address them. Additionally, encouraging collaboration among caregivers, healthcare authorities, and insurance providers is necessary to develop more inclusive treatment plans that are tailored to meet the diverse needs and socioeconomic backgrounds of patients.

Myocardial Infarction as an Initial Presentation of Essential Thrombocythemia With Calreticulin (CALR) Mutation (None Type 1, None Type 2).

Essential thrombocythemia (ET) is one of the classical Philadelphia-negative myeloproliferative neoplasms with different mutations that can be associated with it, like Janus kinase 2 (JAK2), myeloproliferative leukemia protein (MPL), and Calreticulin (CALR) (types 1 and 2). However, there is a lack in the literature concerning other types of CALR mutations and their clinical significance and prognosis. Here we report a 42-year-old male with type 2 diabetes who presented with an inferior ST-elevation myocardial infarction and thrombocytosis. The diagnosis of ET with CALR (neither type 1 nor type 2) was confirmed, which suggests the pathognomonic feature of this mutation.

Acute Limb Ischemia in Pediatric Intensive Care Units.

BACKGROUND: To determine the outcome of children treated for acute limb ischemia (ALI) in pediatric intensive care units (ICUs). METHODS: A single-center, retrospective cohort study including all patients diagnosed with ALI between 2005 and 2022 in 2 different pediatric ICUs: respiratory and cardiac ICU. Data collected included patients demographics and comorbidities, location and cause of arterial occlusion, and type and duration of therapy. Primary end point was freedom from amputation. Secondary end point was all-cause mortality. RESULTS: A total of 78 patients (58% male) with ALI were included in the study. Median age was 3.8 months (range 0.03-201). The lower extremity was involved in 55 (70%) patients. The limb ischemia was caused by arterial instrumentation in 94% of the patients. Anticoagulation was administered as the first-line therapy in all patients. Unfractionated heparin was administered for a median duration of 5 days (range 1-48). Low molecular weight heparin was continued for a median period of 28 days (range 4-420). Thrombolytic therapy was administered in 5 patients and 2 required surgical revascularization, all for failure of anticoagulation therapy. Mean follow-up was 21 months (range 1-188 months). None of the patients required major upper or lower extremity amputations during or after the index admission. Overall survival at 30 months was 68%. The causes of mortalities were unrelated to the limb ischemia. CONCLUSIONS: This large, single-center study demonstrates that ALI in the pediatric ICU population can be treated conservatively and is associated with a low amputation rate following nonoperative management. The favorable outcome exists regardless of the etiology of the ALI and underlying diseases.

Value of Drains in Soft-Tissue Tumour Surgery: A Specialist Regional Centre Experience.

Background The mainstay of therapy in most soft-tissue tumours (STTs) is excision. However, this often results in blood/extracellular fluid collection within large dead spaces necessitating the use of surgical drains. Whether meticulous attention to haemostasis, careful closure of dead space, and use of compression bandage obviates the need for drains was investigated. This study aimed to compare postoperative outcomes in patients undergoing surgery for STTs with and without the use of drains. Methodology A retrospective analysis of patients undergoing STT surgery over five years was undertaken using a regional STT specialist service database. Patients were stratified into the following two groups: compression bandage alone (CB) versus compression bandage with drain (CBD). The chi-square test was used to examine associations with infection, seroma, and haematoma, while the unpaired t-test was used for associations with hospital stay and time to wound healing. The unpaired t-test with Bonferroni correction was used to account for tumour dimensions across both groups. Results A total of 81 CB and 25 CBD patients were included. The mean hospital stay was significantly lower in CB compared to CBD (4.9 days, SD = 8.574 vs. 9.8 days, SD = 7.647, p = 0.0125). None of the other variables was significantly different between the two groups, including infection (21.3% vs. 24.0%, p = 0.7804), seroma (25.0% vs. 36.0%, p = 0.2865), haematoma (0.026% vs. 2.0%, p = 0.2325), and time to wound healing (55.8 days, SD = 63.59 vs. 42.3 days, SD = 58.88, p = 0.3648). Conclusions Our findings suggest that the use of drains in patients undergoing STT tumour surgery lengthens hospital stay without reducing the incidence of postoperative complications/time to wound healing. A larger, prospective trial is needed.

Assessing Bone Marrow Activity with [18F]FLT PET in Patients with Essential Thrombocythemia and Prefibrotic Myelofibrosis: A Proof of Concept.

Objectives: This study aims to assess the value of FLT-PET as a non-invasive tool to differentiate between patients with ET and Pre-PMF. This study is a pilot study to have a proof of concept only. Methods: This is a prospective, interventional study where a total of 12 patients were included. Each patient underwent FLT PET imaging as well as bone marrow examination (gold standard). In addition, semi-quantitative (SUVmax and SUVmean) measurements of FLT uptake in the liver, spleen, and Lspine, SUVmean, as well as the Total Lesion Glycolysis (TLG) of the Lspine were performed. Results from the two patient cohorts were compared using = Kruskal-Wallis statistical test. A P-value of <.05 is considered to be statistically significant. Results: The differences in FLT SUVmax and SUVmean measurements in the three organs (liver, spleen, and LSpine) between the ET and Pre-PMF patients were not statistically significant (P > .05). In contrast, TLG measurements in the LSpine were statistically different (P = .013), and therefore, compared to gold standard bone marrow results, TLG can separate ET and Pre-PMF patients. Conclusion: This study is a proof of concept about the potential to discriminate between ET and pre-PMF patients in a non-invasive way. TLG of the LSpine in FLT PET images is a potential quantitative parameter to distinguish between ET and pre-PMF patients.

Investigating Genetic and Other Determinants of First-Onset Myocardial Infarction in Malaysia: Protocol for the Malaysian Acute Vascular Events Risk Study.

BACKGROUND: Although the burden of premature myocardial infarction (MI) is high in Malaysia, direct evidence on the determinants of MI in this multi-ethnic population remains sparse. OBJECTIVE: The Malaysian Acute Vascular Events Risk (MAVERIK) study is a retrospective case-control study established to investigate the genomic, lipid-related, and other determinants of acute MI in Malaysia. In this paper, we report the study protocol and early results. METHODS: By June 2019, we had enrolled approximately 2500 patients with their first MI and 2500 controls without cardiovascular disease, who were frequency-matched by age, sex, and ethnicity, from 17 hospitals in Malaysia. For each participant, serum and whole blood have been collected and stored. Clinical, demographic, and behavioral information has been obtained using a 200-item questionnaire. RESULTS: Tobacco consumption, a history of diabetes, hypertension, markers of visceral adiposity, indicators of lower socioeconomic status, and a family history of coronary disease were more prevalent in cases than in controls. Adjusted (age and sex) logistic regression models for traditional risk factors indicated that current smoking (odds ratio [OR] 4.11, 95% CI 3.56-4.75; P<.001), previous smoking (OR 1.34, 95% CI 1.12-1.60; P=.001), a history of high blood pressure (OR 2.13, 95% CI 1.86-2.44; P<.001), a history of diabetes mellitus (OR 2.72, 95% CI 2.34-3.17; P<.001), a family history of coronary heart disease (OR 1.28, 95% CI 1.07-1.55; P=.009), and obesity (BMI >30 kg/m2; OR 1.19, 95% CI 1.05-1.34; P=.009) were associated with MI in age- and sex-adjusted models. CONCLUSIONS: The MAVERIK study can serve as a useful platform to investigate genetic and other risk factors for MI in an understudied Southeast Asian population. It should help to hasten the discovery of disease-causing pathways and inform regionally appropriate strategies that optimize public health action. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/31885.

Coexistence of Prefibrotic Myelofibrosis with Monoclonal Gammopathy of Undetermined Significance: A Case Report.

The coexistence of dual hematological neoplasms is an unusual and challenging presentation due to the different combination of etiopathology. The presentation of synchronous dual hematological malignancies can be one of the 3 types: myeloid + lymphoid or dual lymphoid or dual myeloid. Here, we are reporting a case of a 53-year-old male with simultaneous presence of JAK2 V617F-positive myeloproliferative neoplasm with features favoring prefibrotic phase of primary myelofibrosis (pre-PMF) in combination with monoclonal gammopathy of undetermined significance (MGUS). In such cases of simultaneous existence of dual hematological neoplasm management, it is recommended to treat the more aggressive one. Currently, our management plan is focusing on treating the pre-PMF and observation of MGUS with regular monitoring for transformation to MM.

A study of 18F-FLT positron emission tomography/computed tomography imaging in cases of prefibrotic/early primary myelofibrosis and essential thrombocythemia.

The objectives of this research project are to study in patients with primary myelofibrosis (PMF) and Essential Thrombocythemia (ET); (1) the uptake patterns of FLT-PET (FLT-PET) and its value in diagnosing, staging, and treatment response monitoring of malignant hematopoiesis, (2) compare imaging findings from FLT-PET with bone marrow biopsy (standard of care), and (3) associate FLT-PET uptake patterns with genetic makeup such as JAK2 (Janus kinase 2), CALR (Calreticulin), MPL (myeloproliferative leukemia protein), Triple negative disease, and allele burden.This trial is registered in ClinicalTrials.gov with number NCT03116542. Protocol version: Mar 2017.

Outcome of Pregnancy in the Era of PEGylated Interferon-α2a in Females with Chronic Myeloid Leukemia: An Experience from Qatar.

Chronic myelogenous leukemia (CML), also known as chronic myeloid leukemia, is a myeloproliferative neoplasm characterized by increased proliferation of the granulocytic cell line without loss of its capacity to differentiate. It accounts for 20% of all adults affected by leukemia. Tyrosine kinase inhibitors revolutionized the treatment for CML and improved quality of life. Fertility is an important issue for both males and females. Here, we report our experience with a pregnant female with CML, and shed light on safety and efficacy of PEGylated interferon-αa in pregnant women with CML and its outcome.

Outcome of Pregnancy in the Era of Pegylated Interferon Alpha 2a in Females with Essential Thrombocythemia: An Experience from Qatar.

Myeloproliferative neoplasms are a diversified group of diseases of the hematopoietic stem cell, such as essential thrombocythemia (ET) and polycythemia vera. They are mainly caused by mutations in the following genes: JAK2, CALR, and MPL. All carry an increased risk to transform into acute leukemia or chronic myelogenous leukemia along with thrombosis and hemorrhagic complications. Treatment of such disorders during pregnancy is a challenging footstep, given the high risk of complications for both the mother and the fetus. Here, we report about two pregnant females with ET that has been treated with pegylated interferon alpha with safe and effective outcome.

Applicability of Supercritical fluid chromatography-Mass spectrometry to metabolomics. II-Assessment of a comprehensive library of metabolites and evaluation of biological matrices.

In this work, the impact of biological matrices, such as plasma and urine, was evaluated under SFCHRMS in the field of metabolomics. For this purpose, a representative set of 49 metabolites were selected. The assessment of the matrix effects (ME), the impact of biological fluids on the quality of MS/MS spectra and the robustness of the SFCHRMS method were each taken into consideration. The results have highlighted a limited presence of ME in both plasma and urine, with 30% of the metabolites suffering from ME in plasma and 25% in urine, demonstrating a limited sensitivity loss in the presence of matrices. Subsequently, the MS/MS spectra evaluation was performed for further peak annotation. Their analyses have highlighted three different scenarios: 63% of the tested metabolites did not suffer from any interference regardless of the matrix; 21% were negatively impacted in only one matrix and the remaining 16% showed the presence of matrix-belonging compounds interfering in both urine and plasma. Finally, the assessment of retention times stability in the biological samples, has brought into evidence a remarkable robustness of the SFCHRMS method. Average RSD (%) values of retention times for spiked metabolites were equal or below 0.5%, in the two biological fluids over a period of three weeks. In the second part of the work, the evaluation of the Sigma Mass Spectrometry Metabolite Library of Standards containing 597 metabolites, under SFCHRMS conditions was performed. A total detectability of the commercial library up to 66% was reached. Among the families of detected metabolites, large percentages were met for some of them. Highly polar metabolites such as amino acids (87%), nucleosides (85%) and carbohydrates (71%) have demonstrated important success rates, equally for hydrophobic analytes such as steroids (78%) and lipids (71%). On the negative side, very poor performance was found for phosphorylated metabolites, namely phosphate-containing compounds (14%) and nucleotides (31%).

Nilotinib Induced Recurrent Gastric Polyps: Case Report and Review of Literature.

BACKGROUND Tyrosine kinase inhibitors (TKIs) are currently an important targeted drug class in the treatment of chronic myeloid leukemia (CML). Imatinib was the first approved TKI for CML in 2001. Nilotinib is a second-generation TKI, approved in 2007; it inhibits BCR-ABL, PDGFR, and c-KIT, and is 30 times more potent than imatinib. Tyrosine kinase enzymes are expressed in multiple tissues and are involved in several signaling pathways; they have been shown to have several off-target side effects. CASE REPORT We report a case of an elderly male with CML and no history of gastrointestinal diseases, treated with nilotinib, and developed recurrent gastric polyps after three years of treatment. We excluded common causes of gastric polyps and therefore considered nilotinib as a probable cause of recurrent gastric polyps. CONCLUSIONS Recurrent gastric polyps could be a potential side effect of nilotinib treatment. Careful long-term monitoring of patients on TKI therapy is necessary and further long-term studies of TKI side effects are needed.

Acute Myeloid Leukemia With Inv(16)(p13q22) Associated With Hidden Systemic Mastocytosis: Case Report and Review of Literature.

Systemic mastocytosis (SM) is a condition associated with clonal neoplastic proliferation of mast cells. In up to 40% of systemic mastocytosis cases, an associated clonal hematological disease of non-mast cell lineage, such as acute myeloid leukemia (AML), is diagnosed before, simultaneously with, or after the diagnosis of SM. Herein, we report a case of a 30-year-old man diagnosed with AML with inv(16) (p13;q22) CBFB:MYH11. Associated mastocytosis was not noted at diagnosis and was only detected in the bone marrow at time of remission after successful chemotherapy. The diagnosis of mastocytosis was based on the demonstration of a multifocal dense mast cell infiltrate in the marrow biopsy with aberrant immunophenotype, with coexpression of tryptase, CD117, and CD25. The mast cells showed atypical morphology mostly with irregular nuclear contour, bilobed or multilobed nuclei with cytoplasmic hypogranulation or irregular metachromatic granule distribution, and some cells with eccentric nucleus or spindle shape. Reexamination of the pretherapeutic bone marrow with immunostain for tryptase and CD25 revealed that mastocytosis was present from the start but masked by extensive blast proliferation. This case indicates that mast cell infiltrates are sometimes underappreciated at the original diagnosis of AML with inv(16) and that the concurrent diagnosis of SM with AML requires a high index of suspicion supported with comprehensive morphologic and immunohistochemical evaluation for a neoplastic mast cell proliferation.

Development of an improved online comprehensive hydrophilic interaction chromatography × reversed-phase ultra-high-pressure liquid chromatography platform for complex multiclass polyphenolic sample analysis.

In this study, an improved online comprehensive two-dimensional liquid chromatography platform coupled to tandem mass spectrometry was developed for the analysis of complex polyphenolic samples. A narrowbore hydrophilic interaction chromatography column (150 × 2.0 mm, 3.0 µm, cross-linked diol) was employed in the first dimension, while a reversed-phase column based on monodisperse sub-2 µm fully porous particles (50 × 3.0 mm, 1.9 µm d.p.) with high surface area (410 m2 /g) was employed in the second dimension. The combination of a trapping column modulation interface with the high retentive fully porous monodisperse reversed-phase column in the second dimension resulted in higher peak capacity values (1146 versus 867), increased sensitivity, sharper and more symmetrical peaks in comparison with a conventional loop-based method, with the same analysis time (70 min). The system was challenged against a complex polyphenolic extract of a typical Italian apple cultivar, enabling the simultaneous separation of multiple polyphenolic classes, including oligomeric procyanidins, up to degree of polymerization of 10. Hyphenation with an ion trap time-of-flight mass spectrometer led to the tentative identification of 121 analytes, showing how this platform could be a powerful analytical tool for the accurate profiling of complex polyphenolic samples.

Evaluation of two sub-2 µm stationary phases, core-shell and totally porous monodisperse, in the second dimension of on-line comprehensive two dimensional liquid chromatography, a case study: separation of milk peptides after expiration date.

Milk is a rich source of bioactive peptides of great interest for their healthy properties. These peptides are usually encrypted in the sequences of proteins and are released after time dependent proteolysis as very complex hydrolysates. In order to separate and identify the bioactive sequences, we developed an on-line comprehensive two dimensional liquid chromatography approach using the high performance combined with the ultra high performance conditions. A microbore reversed phase (C18 silica, 5 µm) column was employed in first dimension, while, in second dimension, two different UHPLC columns, packed with C18 silica, were tested: a new column based on monodisperse sub-2 µm fully porous particles with high surface area (50 mm × 3.0 mm, 1.9 µm d.p., from Supelco), and a column based on sub-2 µm core-shell particles (50 mm × 3.0 mm, 1.7µm d.p, from Phenomenex(®)). Both set-ups were compared, showing high peak capacity values with respect to a high efficiency monodimensional method, maintaining the same analysis time. Satisfactory selectivity was obtained through the use of different pH between the two dimension, while a very fast continuous shifted gradient in second dimension ensured a good employment of the 2D separation space.

Acute coronary syndrome in women of reproductive age.

BACKGROUND: There is scarce or no data on prevalence and presentation of acute coronary syndrome (ACS) among women of reproductive age. Furthermore, whether women of reproductive age presenting with ACS have the same risk factors as men and older women is not known. OBJECTIVE: To analyze factors associated with ACS in women of reproductive age in comparison with older women and men of a similar age group. METHODOLOGY: A total of 9702 cases of acute coronary syndrome over a 3-year period ( 2006-2008) from the National Cardiovascular Disease database were analyzed, with focus on women of reproductive age (20-<40 years), looking into association with ethnicity, comorbid illness, and the ACS stratum. Comparison with older women (40-<60 years; Control 1) and men of similar age group (Control 2) was made and analyzed using Fisher's exact test and chi-square test when necessary. RESULTS: From a total of 9702 cases, 2344 (24.2%) were women. Of these, 45 (1.9%) were women between 20 and <40 years, which is significantly lower than the two controls (older women 30.8%, and men of same age 6.2%, respectively; P < 0.0001). The distribution of ethnicity shows a similar pattern between the study group and the controls, but patients of Indian ethnicity were over-represented when compared with the Malaysian demographics of general population (31.3% versus 7.1%; P < 0.0001). ACS in women of reproductive age was associated with diabetes mellitus in 37.8%, hypertension in 40.0%, and dyslipidemia in 24.4% of cases, similar to men of the same age but significantly lower than the older women (P < 0.0001). Smoking is not a major risk factor in the study group, where only 6.7% ever smoked, similar to older women (6.8%, P = 1.000) and significantly much less compared with men of the same age (84.1%; P < 0.0001). Regarding the ACS stratum, a significantly higher percentage of women in the study group had ST-segment elevation myocardial infarction compared with older women (P = 0.0085) but less than that of men of similar age (P = 0.0187). CONCLUSION: ACS is rare in women of reproductive age. Diabetes, hypertension, and Indian ethnicity were identified as important contributors.

Incidence of risk factors for developing hyperkalemia when using ACE inhibitors in cardiovascular diseases.

STUDY OBJECTIVE: To determine the incidence of and the risk factors associated with hyperkalemia, induced by ACEI-drug interactions among cardiac patients. SETTING: Five medical and cardiology wards of a tertiary care center in Malaysia. SUBJECTS: Five hundred cardiac inpatients, who received ACEIs concomitantly with other interacting drugs. METHOD: This was a prospective cohort study of 500 patients with cardiovascular diseases admitted to Penang Hospital between January to August 2006, who received ACEIs concomitantly with other interacting drugs. ACEI-drug interactions of clinical significance were identified using available drug information resources. Drug Interaction Probability Scale (DIPS) was used to assess the causality of association between ACEI-drug interactions and the adverse outcome (hyperkalemia). MAIN OUTCOME MEASURE: Hyperkalemia as an adverse clinical outcome of the interaction was identified from laboratory investigations. RESULTS: Of the 489 patients included in the analysis, 48 (9.8%) had hyperkalemia thought to be associated with ACEI-drug interactions. Univariate analysis using binary logistic regression revealed that advanced age (60 years or more), and taking more than 15 medications were independent risk factors significantly associated with hyperkalemia. However, current and previous smoking history appeared to be a protective factor. Risk factors identified as predictors of hyperkalemia secondary to ACEI-drug interactions by multi-logistic regression were: advanced age (adjusted OR 2.3, CI 1.07-5.01); renal disease (adjusted OR 4.7, CI 2.37-9.39); hepatic disease (adjusted OR 5.2, CI 1.08-25.03); taking 15-20 medications (adjusted OR 4.4, CI 2.08-9.19); and taking 21-26 medications (adjusted OR 9.0, CI 1.64-49.74). CONCLUSION: Cardiac patients receiving ACEIs concomitantly with potentially interacting drugs are at high risk of experiencing hyperkalemia. Old age, renal disease, hepatic disease, and receiving large number of medications are factors that may significantly increase their vulnerability towards this adverse outcome; thus, frequent monitoring is advocated.