Prevalence and prognosis of fulminant type 1 diabetes mellitus in The Middle East: a comparative analysis in a 5-year nationwide cohort.

PURPOSE: To analyze the prevalence and progression of fulminant type 1 diabetes (FT1D) in Qatar. METHODS: This retrospective study analyzed consecutive index- diabetic ketoacidosis (DKA) admissions (2015-2020) among patients with new-onset T1D (NT1D) in Qatar. RESULTS: Of the 242 patients, 2.5% fulfilled the FT1D diagnostic criteria. FT1D patients were younger (median-age 4-years vs.15-years in classic-T1D). Gender distribution in FT1D was equal, whereas the classic-T1D group showed a female predominance at 57.6% (n = 136). FT1D patients had a mean C-peptide of 0.11 ± 0.09 ng/ml, compared to 0.53 ± 0.45 ng/ml in classic-T1D. FT1D patients had a median length of stay (LOS) of 1 day (1-2.2) and a DKA duration of 11.25 h (11-15). The median (length of stay) LOS and DKA duration in classic-T1D patients were 2.5 days (1-3.9) and 15.4 h (11-23), respectively. The FT1D subset primarily consisted of moderate (83.3%) and severe 916.7%) DKA, whereas classic T1D had 25.4% mild, 60.6% moderate, and 14% severe DKA cases. FT1D was associated with a higher median white cell count (22.3 × 103/uL) at admission compared to classic T1D (10.6 × 103/uL). ICU admission was needed for 66.6% of FT1D patients, compared to 38.1% of classic-T1D patients. None of the patients in the FT1D group had mortality, while two died in the classic-T1D group. CONCLUSION: This is the first study establishing the existence of FT1D in ME, which presented distinctively from classic-T1D, exhibiting earlier age onset and higher critical care requirements. However, the clinical outcomes in patients with FT1D seem similar to classic T1D.

A systematic review of literature on Insulin-like growth factor-2-mediated hypoglycaemia in non-islet cell tumours.

INTRODUCTION: Insulin-like growth factor-2 (IGF-2)-mediated hypoglycemia is a rare yet clinically significant entity with considerable morbidity and mortality. Existing literature is limited and fails to offer a comprehensive understanding of its clinical trajectory, management and prognostication. METHODS: Systematic review of English-language articles reporting primary patient data on IMH was searched using electronic databases (PubMed, Scopus and Embase) from any date up to 21 December 2022. Data were analysed in STATA-16. RESULTS: The systematic review contains 172 studies, including 1 Randomised controlled trial, 1 prospective observational study, 5 retrospective observational studies, 150 case reports, 11 case series and 4 conference abstracts. A total of 233 patients were analysed, averaging 60.6 ± 17.1 years in age, with comparable proportions of males and females. The commonest tumours associated with Insulin-like Growth Factor-2-mediated hypoglycaemia were fibrous tumours (N = 124, 53.2%), followed by non-fibrous tumours originating from the liver (N = 21, 9%), hemangiopericytomas (N = 20, 8.5%) and mesotheliomas (N = 11, 4.7%). Hypoglycaemia was the presenting feature of NICT in 42% of cases. Predominant clinical features included loss of consciousness (26.7%) and confusion (21%). The mean IGF-2 and IGF-1 levels were 882.3 ± 630.6 ng/dL and 41.8 ± 47.8, respectively, with no significant correlation between these levels and patient outcomes. Surgical removal was the most employed treatment modality (47.2%), followed by medication therapy. The recovery rate was 77%, with chronic liver disease (CLD) significantly associated with a poor outcome (OR: 7.23, P: 0.03). Tumours originating from fibrous tissues were significantly associated with recovery (p < .001). In the logistic regression model, CLD remained a significant predictor of poor outcomes. CONCLUSION: This systematic review highlights that most non-islet-cell tumour-hypoglycaemia (NICTH) is due to fibrous tumours. NICTs demonstrate a variable prognosis, which is fair if originating from fibrous tissue. Management such as octreotide, corticosteroids, diazoxide, embolization, radiotherapy and surgical resection have disparate success rates.

Differential evolution of diabetic ketoacidosis in adults with pre-existent versus newly diagnosed type 1 and type 2 diabetes mellitus.

BACKGROUND: Diabetic ketoacidosis (DKA) was once known to be specific to type-1 diabetes-mellitus (T1D); however, many cases are now seen in patients with type-2 diabetes-mellitus (T2D). Little is known about how this etiology shift affects DKA's outcomes. METHODS: We studied consecutive index DKA admissions from January 2015 to March 2021. Descriptive analyses were performed based on pre-existing T1D and T2D (PT1D and PT2D, respectively) and newly diagnosed T1D and T2D (NT1D and NT2D, respectively). RESULTS: Of the 922 patients, 480 (52%) had T1D, of which 69% had PT1D and 31% NT1D, whereas 442 (48%) had T2D, of which 60% had PT2D and 40% NT2D. The mean age was highest in PT2D (47.6 ± 13.1 years) and lowest in PT1D (27.3 ± 0.5 years) (P < 0.001). Patients in all groups were predominantly male except in the PT1D group (55% females) (P < 0.001). Most patients were Arabic (76% in PT1D, 51.4% in NT1D, 46.6% in PT2D) except for NT2D, which mainly comprised Asians (53%) (P < 0.001). Patients with NT2D had the longest hospital length of stay (LOS) (6.8 ± 11.3 days) (P < 0.001), longest DKA duration (26.6 ± 21.1 h) (P < 0.001), and more intensive-care unit (ICU) admissions (31.2%) (P < 0.001). Patients with PT1D had the shortest LOS (2.5 ± 3.5 days) (P < 0.001), DKA duration (18.9 ± 4.2 h) (P < 0.001), and lowest ICU admissions (16.6%) (P < 0.001). CONCLUSIONS/INTERPRETATION: We presented the largest regional data on differences in DKA based on the type and duration of diabetes- mellitus (DM), showing that T2D is becoming an increasing cause of DKA, with worse clinical outcomes (especially newly diagnosed T2D) compared to T1D.

Incidence of diabetic ketoacidosis does not differ in Ramadan compared to other months and seasons: results from a 6-year multicenter study.

BACKGROUND: Diabetic ketoacidosis (DKA) is a life-threatening adverse complication of patients with diabetes mellitus (DM). It is postulated that fasting during Ramadan can increase the risk of DKA; however, there are contradicting data in this regard. Furthermore, studies from Western countries have suggested a seasonal variation in the incidence of DKA. This study examines the differences in the number of DKA episodes during Ramadan compared to the rest of the year in patients with type 1 DM (T1D) and type 2 DM (T2D). Besides, we aim to examine the seasonal difference in the incidence of DKA. METHODS: We included consecutive index-DKA admissions from 2015 to 2021 and used descriptive statistics to compare the episodes of DKA in Ramadan vs other months and seasons. RESULTS: Of 922 patients, 480 (52%) had T1D, whereas 442 (48%) had T2D. The median age (IQR) was 35 (25-45) years, with the majority being Arab (N = 502, 54.4%). There were 94 DKA admissions in six collective Ramadan months, whereas the DKA admissions ranged from 61 to 88 episodes in other months (p = .3). The highest DKA admissions were observed in Autumn (N = 236) and the lowest in Spring (N = 226) with no statistically significant difference (p = .4). There were no differences in DKA severity or new-onset diabetes rates when analyzed based on Hiji months, Roman months, or seasons. CONCLUSIONS: DKA occurrence is not increased during Ramadan. We found no evidence of seasonal variations in the rates of DKA in the State of Qatar.

Clinical and biochemical determinants of length of stay, readmission and recurrence in patients admitted with diabetic ketoacidosis.

BACKGROUND: The increasing prevalence of diabetic ketoacidosis (DKA) related admissions poses a significant burden on the healthcare systems globally. However, data regarding the predictors of healthcare resource utilization in DKA is limited and inconsistent. This study aimed to identify key predictors of hospital length of stay (LOS), readmission and recurrent DKA episodes. METHODS: We undertook a retrospective cross-sectional analysis of all DKA admissions from 2015 to 2021 across four hospitals in Qatar. The primary outcomes were the length of stay (LOS), 90-day readmission and 6-month and 1-year DKA recurrence. RESULTS: We included 922 patients with a median age of 35 years (25-45). 62% were males with type-1 diabetes-mellitus (T1DM) and type-2 DM (T2DM), present in 52% and 48% of patients. The median LOS was 2.6 days (IQR 1.1-4.8), and the median DKA resolution time was 18 h (10.5-29). Male-gender, new-onset DM, higher Charlson Comorbidity Index (CCI), lower haemoglobin, sodium and potassium, higher urea, longer DKA duration and MICU admission predicted a longer LOS in a multivariate regression analysis. None of the factors were significantly associated with 90-day readmission. Patients with pre-existing T1DM were more likely to have a six-month DKA recurrence than pre-existing T2DM. Patients with a 6-month DKA recurrence, female gender and T1DM had higher odds of 12-month recurrence, whereas a consult with a diabetes educator at the index admission was associated with decreased odds of recurrence. CONCLUSIONS/INTERPRETATION: This is the most extensive study from the Middle-East region reporting on LOS, readmissions and the recurrence of DKA. Results from this study with a diverse population may be valuable for physicians and healthcare systems to decrease the diabetes-related healthcare burden in DKA patients.

Genotypic and Phenotypic Composition of Sickle Cell Disease in the Arab Population - A Systematic Review.

Sickle cell disease (SCD) is a genetic disease influenced by ethnicity and regional differences in its clinical course. Recent advances in the management of SCD with newer therapies are being introduced to the Western population. However, many of these treatments are yet to be used in the Arabic SCD population. Understanding the genetic variations of SCD regionally is essential to anticipate the utilization of new treatments. This systematic review's main objective is to pool the available data on the genetic composition of SCD in the Arabic population. Data for 44,034 patients was extracted from 184 studies (11 case reports, 8 case series, 56 retrospectives, 107 prospective observational studies, and 2 clinical trials) using PubMed, Scopus, and Google Scholar. Male (49%) and female (51%) patients were equally reported wherever gender was available (N=13105). Various SCD genotypes were reported in a total of 14,257 patients, including Hb SS (77%) Hb Sß0 (9.9%), and Hb Sß+ (7.2%), while the rest of the genotypes, including HbSC, HbSD, HbSE, HbSO Arab, Hb S/α-Thal, Hb Sß0 + α-Thal, and HBS Oman were individually reported in <4% of the cases. Major SCD complications in the Arab population included pain crises (48.25%) followed by neurological complications (33.46%), hepatobiliary complications (25.53%), musculoskeletal complications (24.73%), and hemolytic anemia (23.57%). The treatments reported for SCD included hydroxyurea (20%), blood transfusion (14.32%), and Deferasirox (3.03%). We did not find the use of stem cell transplantation or newer treatments such as L-Glutamine, Voxelotor, Crizanlizumab, or gene therapy reported in any of the studies included in our review. This review highlights the genetic makeup of SCD in Arab countries and its common phenotypic manifestations and will help direct further research on SCD in this region, especially concerning genetic therapy. Systematic Review Registration: The protocol has been registered in the International Prospective Register of Systematic Reviews(PROSPERO):CRD42020218,666. https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=218666.

Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Variant in Patients with Philadelphia-Negative Myeloproliferative Neoplasm: A Single Center Experience.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the viral agent responsible for the coronavirus disease of 2019. The disease is primarily a respiratory illness; however, multisystem involvement is not uncommon. The infection is reported to be more severe in patients with multiple comorbidities and immunocompromised patients. Patients with hematological malignancies are immunocompromised and prone to develop severe SARS-CoV-2 infection. The SARS-CoV-2 had developed several mutations that resulted in different strains with different virulence and different degree of protection by vaccination or prior infection. The Omicron variant is reported to cause mild illness; however, the effect on patients with hematological malignancies like myeloproliferative neoplasms (MPNs) is not clear. We present patients with MPNs who had infection with the Omicron variant of the SARS-CoV-2 and their outcomes. METHODS: Retrospective data from the National Center for Cancer Care and Research records from December 20, 2021, to January 30, 2022. Participants were adults over the age of 18 years with Omicron infection who had been diagnosed with Philadelphia-negative MPNs, essential thrombocythemia, polycythemia vera (PV), and primary myelofibrosis according to the 2008/2016 WHO classification for MPN. RESULTS: Twenty-two patients with Philadelphia-negative MPN had Omicron infection. All patients had a mild disease according to the WHO classification of COVID-19 severity. Most of the patients had medical comorbidities, with hypertension being the most common comorbidity. However, only one patient with PV required hospitalization. DISCUSSION/CONCLUSIONS: In patients with Philadelphia-negative MPN, the Omicron variant of SARS-CoV-2 usually results in mild infection.

Clinical image report of acute Cholangitis in Beta-thalassemia major.

Beta-thalassemia is congenital red blood cell disorder. Gallstones is a recognized complication due to recurrent hemolysis. Acute cholangitis is a rare complication might occur in patient with beta-thalassemia. We report a case of acute cholangitis in patient with beta-thalassemia with Gilbert syndrome. We present a case of a young female of Arabic descent with acute abdomen. Workup revealed acute cholangitis with gallstones in the common bile duct. The ERCP was used to extract the stones than cholecystectomy.

SARS-CoV-2 Omicron Variant in Patients With Chronic Myeloid Leukemia: A Retrospective Study.

Background and aims Coronavirus disease 2019 (COVID-19) is caused by a virus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the first pandemic wave, SARS-CoV-2 had developed significant changes and mutations that resulted in the emergence of different strains. Each strain varies in its virulence and disease severity. Most reports have shown that the Omicron variant causes mild illness. Little is known about the impact of Omicron in patients with chronic myeloid leukemia. We present patients with chronic myeloid leukemia who had infection with the Omicron variant of the SARS-CoV-2 and their outcomes. Materials and methods  Retrospective data from the records of the National Center for Cancer Care and Research from December 20, 2021, to January 30, 2022. Participants were adults over the age of 18 years with Omicron infection who had been diagnosed with chronic myeloid leukemia according to World Health Organization classifications from 2008 and 2016. Results Eleven patients with chronic myeloid leukemia had Omicron infection. All patients had a mild disease according to the World Health Organization classification of COVID-19 severity. The majority of patients were young males.  Conclusions In patients with chronic myeloid leukemia, infection with the Omicron variant of the SARS-CoV-2 usually results in mild disease not requiring hospitalization.

SARS-CoV-2 Omicron Variant in Patients With Chronic Lymphocytic Leukemia: Case Series.

The Coronavirus disease 2019 (COVID-19) is considered the largest pandemic in modern history. Since the first case was reported in 2019, several mutations have affected the severe acute respiratory syndrome-Coronavirus-2 (SARS-CoV-2), resulting in the emergence of new strains. These strains vary significantly in severity and transmissibility. The Omicron (B.1.1.529) variant was reported to cause mild disease in those affected, but little is known about the effect of Omicron on patients with chronic lymphocytic leukemia (CLL). We are reporting a case series of three patients with CLL who experienced infection with the SARS-CoV-2 Omicron variant and their outcomes.

Acute chest syndrome in sickle cell disease/HBE patient, A case report.

The presented case will shed some light on one of the rarest complications of HBSE disease, which is acute chest syndrome, and will highlight the management of that complication.

Manifestations of HbSE sickle cell disease: a systematic review.

BACKGROUND: Sickle cell disease (SCD) is commonly encountered in Africa and Middle Eastern countries. The causative mutation in the gene encoding the hemoglobin subunit ß (HBB) leads to various genotypic variants of the disease. This results in varied phenotypes, with a spectrum of complications, from benign to fatal. Hemoglobin SS (HBSS) genotype is associated with most of these complications; hence, it is a severe form of SCD. On the other hand, rare genotypes such as hemoglobin SE (HBSE) are considered benign. There is limited literature about the clinical manifestations and characteristics of patients with HBSE. We pooled all available data describing the phenotypic manifestations of HBSE heterozygote worldwide to perform a systematic review. METHODS: We performed a systematic review according to PRISMA guidelines using PubMed, SCOPUS, and Google Scholar databases. Two independent reviewers (FA and IK) evaluated studies for eligibility and extracted data. We synthesized data on demographics, manifestations, and management of HBSE disease. PROSPERO Registration Number: CRD42021229877. RESULTS: We found 68 HBSE patients reported in the literature. 24 cases were extracted from case reports whereas 44 cases from case series and retrospective studies. Turkey reported the highest number of patients (n = 22). 32 (47%) of the patients were males. The mean age was 20.9 ± 18.26 years. The mean HBS and HBE percentages were 61.1% ± 7.25% and 32.3% ± 5.06%, respectively, whereas the mean hemoglobin was 11.64 ± 1.73 g/dl. Reported manifestations of HBSE disease included acute vaso-occlusive pain crisis (n = 22, 32.3%), splenomegaly (n = 11, 16.1%), hemolytic anemia (n = 10, 14.7%), infections (n = 8. 11.7%), bone infarction (n = 4, 5.8%), gallstones (n = 3, 4.4%), venous thromboembolism (VTE) (n = 2, 2.9%) and stroke (n = 2, 2.9%), and hematuria (n = 2, 2.9%). Death due to HBSE complications was reported in three patients. CONCLUSION: HBSE is a rare genotypic variant of SCD. It has been considered a benign form; however, there are multiple reports of severe complications. Severe complications observed in HBSE disease include vaso-occlusive crisis, acute chest syndrome, stroke, bone marrow embolism, and death.

A Rare Case of Hemoglobin E/Beta-Thalassemia and Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease, with multisystemic involvement. Hemoglobin E/beta-thalassemia (HbE/beta-thalassemia) is the genotype responsible for approximately one-half of all severe beta-thalassemia worldwide. When beta-thalassemia and SLE coexist, SLE seems to have a more severe course. Here we report a 32-year-old female who presented with dizziness and fatigue was found to have severe hemolytic anemia with thrombocytopenia. Upon further evaluation, she was diagnosed with HbE/beta-thalassemia and SLE, which is a very rare association. In SLE patients, anemia usually results from the disease itself, but it is important to think of other coexisting conditions like thalassemia.