Pattern of cephalosporin and carbapenem-resistant Pseudomonas aeruginosa: a retrospective analysis.

Objectives: Despite its financial cost on the world's health care system, Pseudomonas aeruginosa antibiotic resistance has been increasing. Therefore, the goal of this study was to assess the level of antimicrobial resistance to anti-pseudomonas medicines, specifically ß-lactam medications such as cephalosporin and carbapenems. In addition, we evaluate the prevalence of multi-drug resistance to P. aeruginosa, particularly during the years of the COVID-19 pandemic. Methods: This retrospective analysis covered the period from January 2019 to December 2022 and included cephalosporin- and carbapenem-resistant P. aeruginosa isolates. The real-time polymerase chain reaction Genexpert test (CARBA-R kit) was used for the detection of genes responsible for carbapenemase resistance. Results: During the time of the study, 1815 clinical isolates of P. aeruginosa were identified and 160 (9%) were resistant to carbapenems and cephalosporins. The resistance rates were 32.5% (13/597) in 2019, 11.2% (44/393) in 2020, 7% (26/369) in 2021, and 11% (50/456) in 2022. Of those isolates, multidrug-resistant rates were 6.7%, 86.3%, 57.7%, and 56%, per year over the study period. Using Genexpert test, 88 (93.6%) of multidrug-resistant P. aeruginosa were negative for carbapenemase genes. Conclusion: This study emphasizes the alarming patterns of carbapenem and cephalosporin resistance among P. aeruginosa clinical isolates. Furhter surviellance from different centers and different regions is required.

COVID-19 in patients with rheumatological diseases in the Eastern Province of Saudi Arabia.

The severity of the 2019 coronavirus disease (COVID-19) and its effects remain unpredictable. Certain factors, such as obesity, hypertension, and type 2 diabetes mellitus, may increase the severity of the disease. Rheumatology experts suggest that patients with active autoimmune conditions and controlled autoimmune diseases on immunosuppressive therapy may be at higher risk of developing severe COVID-19. In this retrospective observational study, we aimed to examine the patterns of COVID-19 in patients with underlying rheumatological diseases and their association with disease severity and hospital outcomes. A total of 34 patients with underlying rheumatological diseases who tested positive for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) by polymerase chain reaction (PCR) were included between March 2020 and April 2021 at King Fahd Hospital of the University. The study population consisted of 76.47% female and 23.53% male patients, with a mean age ranging from 20 to 40 years. Female gender (p=0.0001) and younger age (p=0.004) were associated with milder disease. The most frequent rheumatological disease was systemic lupus erythematosus (SLE) (38.24%), which was associated with a milder infection (p=0.045). Patients treated with mycophenolate mofetil (MMF) had a milder disease course (p=0.0037). Hypertension was significantly associated with severe COVID-19 disease (p=0.037). There was no significant relationship between SLE and the need for ICU admission. Patients on hydroxychloroquine and MMF tended to develop milder disease, and there was no association between the severity of the infection and the treatment with steroids.

Emergence of Post COVID-19 Vaccine Autoimmune Diseases: A Single Center Study.

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) became a major concern since the announcement that it is a pandemic in early 2020. Vaccine trials were started in November 2020, and completed rapidly due to the urgency to get over the infection. Side effects to vaccines started to be reported. There were minor side effects including site of injection pain and heaviness and constitutional symptoms like fever which are considered minor. One of the rare adverse events is post vaccine new onset autoimmune diseases. Methods: Data were obtained from one center in the eastern province of Saudi Arabia (King Fahd Hospital of University). All patient events reported occurred in the study period March 2021 to February 2022. We identified patients presenting with autoimmune diseases with exclusively new onset presentations. Results: We identified 31 cases of immune-mediated disease: 18 females (58%); 13 males (42%). Only 4 of them (13%) had an autoimmune background before COVID-19 vaccination. The average time between vaccination and new-onset disease symptoms was 7 days. Among all the cases in our study, 7 patients (22.5%) had new-onset vasculitis, 2 cases had IgA vasculitis and 5 cases had ANCA vasculitis, 6 cases had neurological diseases (19.3%), 4 cases (12.9%) had new-onset systemic lupus erythematosus (SLE), 3 cases (9.6%) presented with new-onset inflammatory arthritis, and one had Sjogren's syndrome (3.2%). Conclusion: Our study is unique as it is the first study to include the largest number (31 patients) of new onsets of confirmed autoimmune diseases related to Covid-19 vaccines.

The association between serum ferritin and bilirubin with glycemic control among patients with type 2 diabetes mellitus.

Previous evidence has shown an association between serum ferritin and bilirubin levels in the development of type 2 diabetes mellitus (T2DM) and glycemic control. However, the evidence is scarce in Saudi Arabia. In this study, we aimed to evaluate the association between serum ferritin and bilirubin levels with glycemic control in patients with T2DM. This was a cross-sectional study that involved 153 patients with T2DM recruited from outpatient diabetes clinics. Participants were categorized into two groups: well-controlled and uncontrolled T2DM, based on their glycemic status. We focused on comparing the iron profile and bilirubin levels between these two groups and examining the influence of antidiabetic medications on these parameters. A total of 153 patients with T2DM were included (58.2% women and 41.8% men). In both univariate and multivariate analyses, ferritin levels did not have a statistically significant association with glycemic control. However, patients with well-controlled T2DM had a significantly higher median level of total bilirubin and direct bilirubin than those with uncontrolled T2DM. Only direct bilirubin showed a statistically significant association with FBG less than 130 mg/dl and HbA1c level less than 7.0%. Ferritin level was not associated with glycemic control in patients with T2DM. On the other hand, direct bilirubin level was an independent predictor of better glycemic control. Monitoring direct bilirubin levels could aid in predicting glycemic control in T2DM and could be a potential target for developing antidiabetic medications.

Hepatobiliary manifestations of COVID-19 and their impact on severity and outcomes in a single center in Saudi Arabia.

Recognizing hepatic manifestations of COVID-19 and their impact on the severity and outcome is crucial in managing this emerging pandemic. However, we lack such reported data in Saudi Arabia regarding this clinical entity. This is a retrospective observational study conducted on 387 patients with COVID-19 disease who were hospitalized at King Fahad Hospital of the University from March-September 2020. The total cohort was divided into two groups: liver and non-liver involvement. Then, the frequency of hepatic manifestations was determined, followed by comparing severity and outcome among the two study groups. A total of 387 patients were included, of which 72.87% had hepatic manifestations. The most prevalent abnormalities were high LDH in 308 (79.58%) followed by AST 205 (52.97%), GGTP 124 (31.26%), ALT 74 (19.12%), PT/INR 66 (17.05%), direct bilirubin 51 (12.40%), total bilirubin 46 (11.88%), and low albumin 48 (12.4%). Univariate analyses showed that liver involvement was significantly associated with severe (31.91%) and critical (34.75%) presentation (P<0.001). Multivariate regression analysis showed that the presence of liver involvement was an independent risk factor for severe or critical COVID-19 disease (OR 2.44; P<0.001), longer hospitalization (OR 2.27; P=0.001), and ICU admission (OR 2.27; P=0.006). The current study showed that liver involvement is common in the setting of COVID-19 disease. Such patients had a higher disease severity and a worse clinical outcome.

Clinical outcome of pre-operative blood transfusion for sickle cell disease patients in post-operative complications.

BACKGROUND: Preoperative blood transfusion for patients with sickle cell disease is a debatable topic and it can be lifesaving. Sickle cell disease patients are at high risk for vaso-occlusive crisis due to the large concentration of sickle hemoglobin (HgbS) in their blood. Despite the current extensive research into this disease, there is still no consensus over whether blood transfusion is a preferable preoperative modality among patients undergoing elective surgical procedures. METHOD: A retrospective observational study, which enrolled 204 patients with Sickle cell disease who underwent surgery at King Fahad Hospital of the University (KFHU) over the last five years. The primary objective was to determine whether there is evidence that preoperative blood transfusion for SCD patients undergoing surgical procedures will reduce postoperative complications related to SCD. RESULTS: A total of 204 patients were included, of which 30% had preoperative blood transfusion. Majority of patient 44% had undergone cholecystectomy. On multivariate logistic regression analysis, patients who did not undergo blood transfusion had significantly higher risk to develop post-operative SCD complications (OR = 3.07, P value = 0.002). In addition, they had significantly prolonged hospitalization (OR = 2.22, P value = 0.08). In contrast, patients who received blood transfusion had lower risk for developing post-operative SCD-related complications (OR = 1.87, P value = 0.29), and decrease in the duration of hospitalization by (OR = 0.49, P value = 0.045). CONCLUSION: Our study showed that patients who had not undergone preoperative blood transfusion had higher risk to develop postoperative complications and prolonged hospital stay compared to those who underwent blood transfusion.

The Impact of Vaccination Against SARS-CoV-2 Virus on the Outcome of COVID-19 Disease.

Background: Coronavirus disease 2019 (COVID-19) is a rapidly spreading infection that is on the rise. New variants are continuously appearing with variable degrees of lethality and infectivity. The extensive work since the start of the pandemic has led to the evolution of COVID-19 vaccines with varying mechanisms. We aim to determine real-world data by looking at the different clinical outcomes associated with COVID-19 vaccination, focusing on the rate of hospitalization, severity, and mortality. Methodology: A retrospective observational study included 624 patients with COVID-19 infection who were hospitalized at King Fahad Hospital of the University and King Fahad Military Medical City between April and July 2021. The cohort was divided into 3 groups: unvaccinated, partially vaccinated (PV), and fully vaccinated (FV). The severity and outcome of COVID-19 disease were compared among the three groups. Among the vaccinated group, we studied the effect of vaccine type on the severity and outcome of COVID-19 disease. Results: We found that 70.4% of patients with COVID-19 disease who required hospitalization were unvaccinated. Un-vaccination was a significant predictor of critical COVID-19 disease (OR 2.31; P <0.001), whereas full vaccination was associated with significantly milder disease severity (OR 0.36; P 0.01). Moreover, un-vaccination status was an independent predictor of longer hospitalization (OR 3.0; P <0.001), a higher requirement for ICU admission (OR 4.7; P <0.001), mechanical ventilation (OR 3.6; P <0.001), and death (OR 4.8; P <0.001), whereas the FV group had a lower risk of ICU admission (OR 0.49; P 0.045). Unvaccinated patients with comorbidities had worse severity and outcome of COVID-19 infection (P<0.05). Both vaccine types (Pfizer and AstraZeneca) had similar protective effects against the worst outcomes of COVID-19 disease. Conclusion: COVID-19 vaccination has been shown to be effective in reducing hospitalization, the severity of COVID-19 infection, and improving outcomes, especially in high-risk group patients. COVID-19 vaccination programs should continue to improve the outcome of such a disease.

A novel stacking ensemble for detecting three types of diabetes mellitus using a Saudi Arabian dataset: Pre-diabetes, T1DM, and T2DM.

Glucose is the primary source of energy for cells, which are the building blocks of life. It is given to the body by insulin that carries out the metabolic tasks that keep people alive. Glucose level imbalance is a sign of diabetes mellitus (DM), a common type of chronic disease. It leads to long-term complications, such as blindness, kidney failure, and heart disease, having a negative impact on one's quality of life. In Saudi Arabia, a ten-fold increase in diabetic cases has been documented within the last three years. DM is broadly categorized as Type 1 Diabetes (T1DM), Type 2 Diabetes (T2DM), and Pre-diabetes. The diagnosis of the correct type is sometimes ambiguous to medical professionals causing difficulties in managing the illness progression. Intensive efforts have been made to predict T2DM. However, there is a lack of studies focusing on accurately identifying T1DM and Pre-diabetes. Therefore, this study aims to utilize Machine Learning (ML) to distinguish and predict the three types of diabetes based on a Saudi Arabian hospital dataset to control their progression. Four different experiments have been conducted to achieve the highest results, where several algorithms were used, including Support Vector Machine (SVM), Random Forest (RF), K-Nearest Neighbor (K-NN), Decision Tree (DT), Bagging, and Stacking. In experiments 2, 3, and 4, the Synthetic Minority Oversampling Technique (SMOTE) was applied to balance the dataset. The empirical results demonstrated promising results of the novel Stacking model that combined Bagging K-NN, Bagging DT, and K-NN, with a K-NN meta-classifier attaining an accuracy, weighted recall, weighted precision, and cohen's kappa score of 94.48%, 94.48%, 94.70%, and 0.9172, respectively. Five principal features were identified to significantly affect the model accuracy using the permutation feature importance, namely Education, AntiDiab, Insulin, Nutrition, and Sex.

The impact of obesity on hospitalized patients with COVID-19 infection in the Eastern Province of Saudi Arabia.

This study aimed to assess the association of obesity with the severity and outcome of COVID-19 infection. A retrospective observational study was performed from March to September 2020 in Saudi Arabia. Baseline and laboratory data were collected from the inpatient health record system. The cohort was divided into three groups based on body mass index. Following this, the severity and outcome of COVID-19 disease were analyzed between the three groups. Of the 502 COVID-19 cases included, 244 (48.5%) were obese. Obesity was significantly associated with severe (53.5%) or critical (28%) COVID-19 infection (P<0.001) and a higher need for ICU admission (35.8%, P=0.034). Multivariate analysis showed that overweight/obesity was an independent risk factor of severe (P<0.001) as well as critical COVID-19 infection (P=0.026, respectively) and a predictor of a higher risk of ICU admission (P=0.012). Class I obesity was associated with severe-critical COVID-19 disease (33.6%, P=0.042) compared to other obesity classes. Obesity is an independent risk factor for severe-critical COVID-19 infection and a higher risk of ICU admission. Clinicians should give special attention to such populations and prioritize vaccination programs to improve outcomes.

Gastrointestinal manifestations of COVID-19 in a single center in the Eastern Province of Saudi Arabia.

Background: Several gastrointestinal (GI) symptoms have been associated with novel coronavirus disease-2019 (COVID-19). Their prevalence and relation to the severity and hospital outcome of COVID-19 have not been well reported in the Middle East and Saudi Arabia. We aimed to examine the GI manifestations of COVID-19 and their association with the severity and hospital outcome of COVID-19 infection. Methods: We conducted a retrospective observational study of hospitalized COVID-19 patients who had a positive SARS-COV2 PCR test and were admitted at a university hospital in Saudi Arabia, from March to September 2020. The primary objective of the study was to describe the GI manifestations of COVID-19. The secondary objective was to investigate the association of GI manifestations with severity and outcome of COVID-19 infection. Results: We included 390 patients, of which 111 (28.5%) presented with GI manifestations. The most common presentation was diarrhea followed by nausea, vomiting, and abdominal pain. Patients without GI manifestations had a higher risk of severe-critical COVID-19 infection evident by the development of lung infiltration in more than 50% of lung fields within 24-48 h, acute respiratory distress syndrome, altered mental status, multiorgan failure, and cytokine storm syndrome (P < 0.05). These patients had a higher mortality rate compared to patients with GI manifestations (P = 0.01). A lower odds of death was seen among patients with GI symptoms (AOR 0.36; 95% CI, 0.158-0.82; P = 0.01). Conclusion: COVID-19 infection presents commonly with GI manifestations. Patients with GI manifestations have less severe COVID-19 disease and lower mortality rates.

The Impact of Vitamin D Level on the Severity and Outcome of Hospitalized Patients with COVID-19 Disease.

PURPOSE: The world is experiencing a life-altering and extraordinary situation in response to the COVID-19 pandemic. There are limited data and controversies regarding the relationship between vitamin D (Vit D) status and COVID-19 disease. Thus, this study was designed to investigate the association between Vit D levels and the severity or outcomes of COVID-19 disease. METHODS: A cross-sectional observational study was conducted in the Eastern province of Saudi Arabia from January to August 2021. All the admitted patients who were diagnosed with COVID-19 infection were distributed into three groups depending on their Vit D levels: normal, insufficiency, and deficiency. For the three groups, demographic data, and laboratory investigations as well as data regarding the severity of COVID-19 were collected and analysed. RESULTS: A total of 203 diagnosed cases of COVID-19 were included in this study. The Vit D level was normal (>30) in 31 (15.3%) cases, insufficient in 45 (22.2%) cases and deficient in 127 (62.6%) cases. Among the included cases, 58 (28.6%) were critical cases, 109 (53.7%) were severe and 36 (17.7%) had a mild-moderate COVID-19 infection. The most prevalent comorbidity of patients was diabetes mellitus 117 (57.6%), followed by hypertension 70 (34.5%), cardiac disease 24 (11.8%), chronic kidney disease 19 (9.4%) and chronic respiratory disease in 17 (8.4%) cases. Importantly, the current study did not detect any significant association between Vit D status and COVID-19 severity (p-value=0.371) or outcomes (hospital stay, intensive care units admission, ventilation, and mortality rate) (p-value > 0.05), even after adjusting the statistical model for the confounders. CONCLUSION: In hospital settings, Vit D levels are not associated with the severity or outcomes of COVID-19 disease. Further, well-designed studies are required to determine whether Vit D status provides protective effects against worse COVID-19 outcomes.

Effect of nocturnal hypoxemia on glycemic control among diabetic Saudi patients presenting with obstructive sleep apnea.

Background: Obstructive sleep apnea (OSA) is a prevalent disease that is associated with an increased incidence of type II diabetes mellitus (DM) if left untreated. We aimed to determine the association between glycosylated hemoglobin (HbA1c) levels and both nocturnal hypoxemia and apnea-hypopnea index (AHI) among a Saudi patients with OSA. Methods: A cross-sectional study that enrolled 103 adult patients diagnosed with DM and confirmed to have OSA by full night attended polysomnography between 2018 and 2021. Those who presented with acute illness, chronic obstructive pulmonary disease (COPD)/restrictive lung diseases causing sleep-related hypoxemia, or no available HbA1c level within 6 months before polysomnography were excluded from the study. Univariate and multivariate linear regression analyses between HbA1c levels and parameters of interest were tested. Results: Sixty-seven (65%) of the studied population had uncontrolled DM (HbA1c ≥7%). In univariate regression analysis, there was a significant positive association between HbA1c, and sleep time spent with an oxygen saturation below 90% (T90), female gender, and body mass index (BMI) (p<0.05) but not AHI, or associated comorbidities (p>0.05). In the multivariate analysis, HbA1c was positively associated with increasing T90 (p<0.05), and ODI (p<0.05), but not with AHI (p>0.05). Conclusion: Nocturnal hypoxemia could be an important factor affecting glycemic control in patients with OSA suffering from DM irrespective of the severity of both diseases.

The Impact of Diabetes Mellitus and Hyperglycemia on the Severity and Outcome of Patients with COVID-19 Disease: A Single-Center Experience.

PURPOSE: Diabetes mellitus (DM) has been reported to be associated with a  worse outcome of COVID-19 infection. The evidence is scarce in the Middle East and Saudi Arabia. We aimed to evaluate the impact of diabetes mellitus and hyperglycemia in non-diabetic individuals on the severity and outcome of COVID-19 infection. METHODS: This is a retrospective observational study, which included patients with confirmed COVID-19 infection [RT-PCR positive for SARS-CoV2] who were admitted to King Fahd Hospital of the University-Khobar-Eastern Province-Saudi Arabia from March to September 2020. Baseline demographic data, laboratory investigations, and markers of the severity of COVID-19 were analyzed. The collected data were categorized according to the Saudi Arabian Ministry of Health COVID-19 infection severity criteria. Patients were divided into three groups as follows: patients in Group 1 had pre-existing DM, patients in Group 2 did not have DM but were documented to have hyperglycemia at presentation, and patients in Group 3 were neither diabetics nor hyperglycemics at presentation and served as the control group. The severity and outcome of the control group were compared with the other two groups. The effect of risk factors on the severity and outcome of COVID-19 infection was studied in the DM group. RESULTS: A total of 414 patients were included (70.5% males and 29.5% females). The mean age (SD) of patients was 52.3 (±15.5) years. Compared to the control group, pre-existing DM was found to be significantly associated with severe (OR 3.61), critical disease (OR 4.32), intensive care unit (ICU) admission (OR 2.0), and death (OR 2.0) from COVID-19 infection. Hyperglycemia without known DM was also found to be associated with critical COVID-19 pneumonia (P 0.001), and had longer duration of hospitalization (P 0.014), higher ICU admission, mechanical ventilation, and death from COVID-19 infection (P < 0.0001). CONCLUSION: Diabetes mellitus and hyperglycemia at presentation, even in the absence of pre-existing DM, are independent risk factors for disease severity and worse outcome of COVID-19 infection. These patients should be identified and managed accordingly. The COVID-19 vaccination program should also target those populations to improve their outcomes.

Baseline MRI findings as predictors of hypopituitarism in patients with non-functioning pituitary adenomas.

Hypopituitarism tends to occur in large pituitary adenomas. However, similar tumors could present with strikingly different hormonal deficiencies. In this study, we looked at MRI characteristics in non-functioning pituitary adenomas (NFPA), which could predict secondary adrenal insufficiency (SAI) and central hypothyroidism (CHT). We reviewed the files of patients with NFPA attending our clinic. Tumor size, invasiveness, MR-signal intensity, and gadolinium enhancement in preoperative MRI were recorded along with documented presurgical hypopituitarism profile. Logistic regression was used to predict SAI, CHT, or both (SAI/CHT) based on MRI and demographic parameters. Receiver operating characteristic curves were used to determine their diagnostic utility. One hundred twenty-one patients were included in the study. Older age (P = 0.021), male sex (P = 0.043), stalk deviation (P < 0.0001), contrast enhancement (P = 0.029), and optic chiasma compression (P = 0.012) were associated with SAI/CHT. Adenoma vertical height, largest diameter, and estimated volume were also strongly associated with SAI/CHT (P < 0.0001). These associations remained significant in a multivariate analysis. No tumor smaller than 12 mm in vertical height, 17 mm in largest diameter, or 0.9 cm3 in volume was associated with SAI/CHT. At cut-off ≥18 mm for vertical height, ≥23 mm for largest diameter, and ≥3.2 cm3 the sensitivity was around 90-92% for detecting SAI/CHT. Only vertical height was significantly associated with any one or more pituitary hormonal deficit (P = 0.001). In conclusion, adenoma size, independent of the measurement used, remains the best predictor of SAI/CHT in NFPA. Dynamic testing to rule out SAI is probably indicated in adenomas larger than 18 mm vertical height, 23 mm largest diameter and 3.2 cm3 adenoma volume.

Gastrointestinal perforation secondary to COVID-19: Case reports and literature review.

INTRODUCTION: Corona virus disease-2019 (COVID-19) presents primarily with respiratory symptoms. However, extra respiratory manifestations are being frequently recognized including gastrointestinal involvement. The most common gastrointestinal symptoms are nausea, vomiting, diarrhoea and abdominal pain. Gastrointestinal perforation in association with COVID-19 is rarely reported in the literature. PATIENT CONCERNS AND DIAGNOSIS: In this series, we are reporting 3 cases with different presentations of gastrointestinal perforation in the setting of COVID-19. Two patients were admitted with critical COVID-19 pneumonia, both required intensive care, intubation and mechanical ventilation. The first one was an elderly gentleman who had difficult weaning from mechanical ventilation and required tracheostomy. During his stay in intensive care unit, he developed Candidemia without clear source. After transfer to the ward, he developed lower gastrointestinal bleeding and found by imaging to have sealed perforated cecal mass with radiological signs of peritonitis. The second one was an obese young gentleman who was found incidentally to have air under diaphragm. Computed tomography showed severe pneumoperitoneum with cecal and gastric wall perforation. The third case was an elderly gentleman who presented with severe COVID-19 pneumonia along with symptoms and signs of acute abdomen who was confirmed by imaging to have sigmoid diverticulitis with perforation and abscess collection. INTERVENTIONS: The first 2 cases were treated conservatively. The third one was treated surgically. OUTCOME: Our cases had a variable hospital course but fortunately all were discharged in a good clinical condition. CONCLUSION: Our aim from this series is to highlight this fatal complication to clinicians in order to enrich our understanding of this pandemic and as a result improve patients' outcome.

Liver Metastasis in a Young Female Secondary to Breast Cancer: A Case Report.

Breast cancer is common among females worldwide and is most commonly reported in women aged 30-40 years and less commonly in those aged <30 years. Presentation with liver metastasis is rare in breast cancer at all ages. Lactic acidosis in association with metastatic breast cancer is also rare. Here, the authors report a case of a 26-year-old female who presented with cholestatic jaundice, coagulopathy and ascites. Radiological examination showed evidence of infiltrating liver lesion. Computed tomography-guided liver biopsy confirmed the diagnosis of adenocarcinoma of breast origin based on the strong estrogen receptor positivity. Chemotherapy could not be initiated because of the patient's critical condition. Unfortunately, the condition deteriorated rapidly, and the patient died secondary to liver failure manifested with disseminated intravascular coagulation and lactic acidosis. This is a rare case of breast cancer in terms of age group (<30 years), site of metastasis at presentation and complication of metastatic breast cancer (type B lactic acidosis), and thus highlights the distinct features of such breast cancers.

Glucocorticoid resistance syndrome caused by a novel NR3C1 point mutation.

Glucocorticoid resistance syndrome (GRS) is a rare genetic disorder caused by inactivating mutations of the NR3C1 gene which encodes the glucocorticoid receptor. The phenotypic spectrum is broad but typically include symptoms of adrenal insufficiency, mineralocorticoid excess and hyperandrogenism. We report a new case associated with a novel NR3C1 mutation. A 55-year-old woman with lifelong history of low body weight, hyperandrogenism and anxiety was seen at the endocrine clinic after left adrenalectomy and salpingoophorectomy for lesions suspicious of ovarian cancer and adrenal metastasis. The tumors turned out to be a 3.5 cm benign ovarian serous adenofibroma and a 3.5 cm multinodular adrenal mass. She complained of worsened fatigue and inability to recover weight lost with surgery. Pre-operative serum and urinary cortisol were elevated, but she had no stigma of Cushing's syndrome. Plasma ACTH was elevated and a 1-mcg cosyntropin stimulation test was normal. Her fatigue persisted over ensuing years and ACTH-dependent hypercortisolemia remained stable. Low dose oral dexamethasone failed to suppress endogenous cortisol. A pituitary MRI was normal but revealed incidental brain aneurysms. Bone densitometry showed profound osteoporosis. On the bases of this contradictory clinical picture, glucocorticoid resistance syndrome (GRS) was suspected. Using next generation sequencing technology, a novel heterozygous pathogenic variant in the NR3C1 gene was detected. We speculate that vascular malformations and profound osteoporosis, findings associated to cortisol excess, reflect in our patient a variable tissue sensitivity to glucocorticoids. In conclusion, in patients with clinically unexpected ACTH-dependent hypercortisolemia, primary glucocorticoid resistance (GRS) should be considered.

Tuberculosis-associated Immune Thrombocytopenia: A Case Report.

Various hematological manifestations are known to occur with tuberculosis (TB), but its association with immune thrombocytopenia is uncommon and not well recognized. Here, the case of a 39-year-old male who presented with a history of epistaxis and hematuria is described. The patient was found to have diffuse lymphadenopathy both clinically and radiologically. He was diagnosed with immune thrombocytopenia; however, there was a delay in the diagnosis of TB because of the patient's refusal of lymph node biopsy and late recognition of the association between TB and immune thrombocytopenia. Treatment with steroids without antituberculosis medications may have led to reactivation and dissemination of tuberculous infection in this patient. Later, the patient was readmitted with a suspected community-acquired pneumonia and the sputum smear was positive for acid-fast bacilli. Unfortunately, the patient died after he developed sepsis and multiorgan failure. The purpose of this case report is to highlight this rare combination and create awareness among clinicians to consider TB as an underlying etiology of immune thrombocytopenia, especially if there are other associated physical findings such as the presence of lymphadenopathy.