Molecular interactions between metformin and D-limonene inhibit proliferation and promote apoptosis in breast and liver cancer cells.

BACKGROUND: Cancer is a fatal disease that severely affects humans. Designing new anticancer strategies and understanding the mechanism of action of anticancer agents is imperative. HYPOTHESIS/PURPOSE: In this study, we evaluated the utility of metformin and D-limonene, alone or in combination, as potential anticancer therapeutics using the human liver and breast cancer cell lines HepG2 and MCF-7. STUDY DESIGN: An integrated systems pharmacology approach is presented for illustrating the molecular interactions between metformin and D-limonene. METHODS: We applied a systems-based analysis to introduce a drug-target-pathway network that clarifies different mechanisms of treatment. The combination treatment of metformin and D-limonene induced apoptosis in both cell lines compared with single drug treatments, as indicated by flow cytometric and gene expression analysis. RESULTS: The mRNA expression of Bax and P53 genes were significantly upregulated while Bcl-2, iNOS, and Cox-2 were significantly downregulated in all treatment groups compared with normal cells. The percentages of late apoptotic HepG2 and MCF-7 cells were higher in all treatment groups, particularly in the combination treatment group. Calculations for the combination index (CI) revealed a synergistic effect between both drugs for HepG2 cells (CI = 0.14) and MCF-7 cells (CI = 0.22). CONCLUSION: Our data show that metformin, D-limonene, and their combinations exerted significant antitumor effects on the cancer cell lines by inducing apoptosis and modulating the expression of apoptotic genes.

Significance of Triazole in Medicinal Chemistry: Advancement in Drug Design, Reward and Biological Activity.

One of the triazole tautomers, 1,2,4-triazole derivatives, has a wide range of biological activities that suggest its potential therapeutic utility in medicinal chemistry. These actions include anti-inflammatory, anti-cancer, anti-bacterial, anti-tuberculosis, and anti-diabetic effects. The review highlights anti-inflammatory effect of 1,2,4-triazoles in relation to their ability to disrupt significant inflammatory mediators and pathways. We present in-silico data that illuminate the triazoles capacity to inhibit cell division, encourage apoptosis, and stop metastasis in a range of cancer models. This review looks at the bactericidal and bacteriostatic properties of 1,2,4-triazole derivatives, with a focus on their potential efficacy against multi-drug resistant bacterial infections and their usage in tuberculosis therapy. In order to better understand these substances' potential anti-diabetic benefits, this review also looks at how they affect glucose metabolism regulation and insulin responsiveness. Based on information provided, it can be concluded that 1,2,4-triazole derivatives are a promising class of diverse therapeutic agents with potential utility in a range of disorders. Their development and improvement might herald a new era of medical care that will be immensely advantageous to both patients and medical community as a whole. Additionally, this study encourages more research into these substances and their enhancement for use in pharmaceutical development.

Modulatory effects of Moringa oleifera leaf extract on sodium nitrate-induced experimental colitis via regulation of P53, Ki-67 and PCNA biomarkers.

BACKGROUND: Ulcerative colitis is a risk factor for colorectal carcinoma. Different mechanisms are related to colitis like apoptosis and hyperproliferation. Moringa oleifera leaves extract (MO) provides a promising option to overcome the risk. PURPOSE: To examine the colonic changes in a rat model of colitis induced by sodium nitrate (SN) and study the effects of MO. STUDY DESIGN: Eight adult male rats were allocated in each of the three group; control (distilled water), SN (100 mg/kg/day, orally via gastric gavage), and SN + MO (100 mg/kg/day, orally via gastric gavage). METHODS: Body weight was measured after the end of the experiment. Colonic homogenates were tested for levels of oxidative stress indicators. Immunohistochemistry for P53, PCNA and Ki-67 was performed. Fresh colon specimens were used for quantitative real-time PCR for assessment of P53, PCNA and Ki-67 gene expression. RESULTS: SN group revealed a significant decreased weight (p = 0.002). MDA and NO levels were higher with SN administration than with MO co-administration (p= 0.04, 0.01 respectively). GSH level was reduced in SN group (p = 0.02) and significantly increased with MO intake (p = 0.04). SN-induced colonic destructive changes were reversed with MO. P53, PCNA and Ki-67 levels of gene expression were reduced in SN + MO group than SN group (P = 0.007, 0.02, 0.001 respectively). CONCLUSION: MO protected the colonic mucosa against SN-induced changes regulating apoptosis, and cell proliferation.

Development of WHO Recommendations for the Final Phase of Elimination and Prevention of Re-Establishment of Malaria.

The WHO recommends that all affected countries work toward the elimination of malaria, even those still experiencing a high burden of disease. However, malaria programs in the final phase of elimination or those working to prevent re-establishment of transmission after elimination could benefit from specific evidence-based recommendations for these settings as part of comprehensive and quality-controlled malaria guidelines. The WHO convened an external guideline development group to formulate recommendations for interventions to reduce or prevent malaria transmission in areas with very low- to low-transmission levels and those that have eliminated malaria. In addition, several interventions that could be deployed in higher burden areas to accelerate elimination, such as mass drug administration, were reviewed. Systematic reviews were conducted that synthesized and evaluated evidence for the benefits and harms of public health interventions and summarized critical contextual factors from a health systems perspective. A total of 12 recommendations were developed, with five related to mass interventions that could be deployed at higher transmission levels and seven that would be most appropriate for programs in areas close to elimination or those working to prevent re-establishment of transmission. Four chemoprevention, two active case detection, and one vector control interventions were positively recommended, whereas two chemoprevention and three active case detection interventions were not recommended by the WHO. None of the recommendations were classified as strong given the limited and low-quality evidence base. Approaches to conducting higher quality research in very low- to low-transmission settings to improve the strength of WHO recommendations are discussed.

How Ready are Pediatricians and Family Physicians in Saudi Arabia to Perform Clinical Screening of Developmental Dysplasia of the Hip?

Background: Developmental dysplasia of the hip (DDH) is one of the most common hip pathologies in pediatric age group and late diagnosis remains a major concern in Saudi Arabia. Objective: The aim of this study is to examine the ability of Saudi Arabian pediatricians and family physicians to conduct clinical screening for (DDH) by estimating their clinical knowledge and skills and analyzing the gaps therein to determine whether there is potential to launch a national screening protocol for DDH in Saudi Arabia. Methods: This is a multicenter cross-sectional study from three major regions in Saudi Arabia (Central, Eastern and Western provinces). The assessed aspects are risk factors, age of screening, incidence in Saudi Arabia, physical signs and diagnostic markers, and treatment, along with their 'clinical knowledge and skills' score. Results: Half of the participants were pediatricians, while the rest were family physicians. More than a third of the participants were considered to have adequate knowledge, ie, above the mean score. Dimensions with the most significant knowledge gaps included the incidence of DDH in Saudi Arabia, adverse effects of swaddling, and the management of a high-risk infants presenting with a negative physical examination. Additionally, there were relatively low rates of awareness regarding positive risk factors as well as a generally poor ability to identify physical signs. Clinical knowledge and skill levels were significantly lower among family physicians. Conclusion: Pediatricians and family physicians in Saudi Arabia still need further training to improve their clinical skills for DDH screening. The proper administration of training programs could eventually enable the gradual implementation of a national systematic screening program.

The Modified Bosniak Classification for Intermediate and High-Risk Renal Cysts.

Background Renal cysts are uncommon among the pediatric population, and their transformation into malignant lesions is also uncommon. Early detection can prevent further complications and protect renal function. Bosniak classification is a computed tomography-based classification for renal cysts developed for adults. Children are more susceptible to CT radiation. Therefore, a modified Bosniak classification for children based on the ultrasound (US) can be used if it shows reliability and accuracy. Aim To apply the modified Bosniak classification system among children with renal cysts. Methods This was a retrospective study that was conducted on pediatric patients who underwent surgery for intermediate and high-risk complex renal cysts in Prince Sultan Military Medical City, Riyadh, Saudi Arabia using radiological information from 2009 to 2022. The collected data included demographics, medical history, radiological findings, and characteristics of renal cysts. SPSS Statistics v. 22 (IBM Corp., Armonk, NY) was used to analyze the data. Results There were 40 children included in the study based on the US-modified Bosniak classification. Around 26.3% of patients had class I and 39.5% had class II renal cysts. Histopathology showed that 10% had Wilms tumor, and 15% had benign lesions. There were significant correlations between pathology findings and US findings (p=0.004), and CT findings (p=0.016). Conclusion The modified Bosniak classification based on the US is sensitive, specific, and sufficiently accurate in the classification of renal cysts among children. Also, the size of the renal cysts can be a diagnostic marker of differentiation of benign and malignant cysts with high sensitivity and specificity.

Acute gastroenteritis-related acute kidney injury in a tertiary care center.

BACKGROUND: Acute gastroenteritis (AGE) can cause acute kidney injury (AKI) via hypoperfusion mechanisms. Early detection of AKI caused by AGE can significantly decrease mortality rates. In Saudi Arabia, studies investigating the association between AGE and AKI are limited; thus, we aimed to fill this knowledge gap. OBJECTIVES: Analyze all cases of AGE reported in tertiary-care hospitals to assess the prevalence of AKI among AGE patients. DESIGN: Retrospective cohort SETTINGS: Single tertiary-care center PATIENTS AND METHODS: The study included patients treated for AGE between October 2017 and October 2022. Stool culture was used to diagnose AGE. Inclusion criteria were infective diarrhea and/ or vomiting, and availability of data (demographics, comorbidities, malignancies, length of hospital stay, vital signs at the time of diagnosis, dehydration, causative agents of diarrhea, hemodialysis status, and laboratory data. MAIN OUTCOME MEASURES: Prevalence of AKI among AGE patients and factors associated with development of AKI. SAMPLE SIZE: 300 patients diagnosed with AGE. RESULTS: Of the 300 patients with AGE, 41 (13.6%) had AKI, those older than 60 years were more likely to develop AKI. The most frequent cause of AGE was Salmonella spp. (n=163, 53.3%), whereas AKI was most common in Clostridium difficile AGE patients (n=21, 51.2%). Furthermore, the most common comorbidity in the present study was malignancy, especially leukemia and lymphoma the risk of AKI was independently associated with mild dehydration, higher serum urea concentrations and low GFR values. CONCLUSIONS: Patients hospitalized for diarrheal disease are at an increased risk of developing AKI due to dehydration and comorbid conditions. It is crucial to keep kidney function in mind for AGE patients as this is associated with a high mortality rate and poor prognosis. LIMITATIONS: The main limitation of this study was its retrospective design. Another limitation is that it is limited to a single center. CONFLICTS OF INTEREST: None.

Intranasal Delivery of a Silymarin Loaded Microemulsion for the Effective Treatment of Parkinson's Disease in Rats: Formulation, Optimization, Characterization, and In Vivo Evaluation.

A mucoadhesive microemulsion of lipophilic silymarin (SLMMME) was developed to treat Parkinson's disease (PD). Optimization of the SLM microemulsion (ME) was performed using Central Composite Design (CCD). The composition of oil, surfactant, co-surfactant, and water was varied, as per the design, to optimize their ratio and achieve desirable droplet size, zeta potential, and drug loading. The droplet size, zeta potential, and drug loading of optimized SLMME were 61.26 ± 3.65 nm, -24.26 ± 0.2 mV, and 97.28 ± 4.87%, respectively. With the addition of chitosan, the droplet size and zeta potential of the developed ME were both improved considerably. In vitro cell toxicity investigations on a neuroblastoma cell line confirmed that SLMMME was non-toxic and harmless. In comparison to ME and drug solution, mucoadhesive ME had the most flow through sheep nasal mucosa. Further, the in vitro release showed significantly higher drug release, and diffusion of the SLM loaded in MEs than that of the silymarin solution (SLMS). The assessment of behavioral and biochemical parameters, as well as inflammatory markers, showed significant (p < 0.05) amelioration in their level, confirming the significant improvement in neuroprotection in rats treated with SLMMME compared to rats treated with naïve SLM.

Factors influencing the quality of life of GERD patients in the Aseer Region, Saudi Arabia.

Gastroesophageal reflux disease (GERD) is a common upper gastrointestinal disorder characterized by troublesome symptoms, including heartburn and acid regurgitation. GERD is associated with complications such as peptic stricture, Barrett's esophagus, and esophageal adenocarcinoma, and it negatively affects quality of life (QoL). Aims: To assess the factors influencing the QoL of GERD patients in the Aseer region of Saudi Arabia. Settings and Design: This descriptive cross-sectional study used self-administered questionnaires in a study population of patients aged ≥18 years from Aseer, Saudi Arabia, between January 15, 2023-February 15, 2023. Materials and Methods: A previously validated GERD health-related QoL (GERD-HRQoL) questionnaire was used to assess the patients' sociodemographic data, GERD, and GERD-HRQoL. Statistical Analysis Used: Descriptive analysis included describing the frequency distribution and percentage for study variables, including demographic data, GERD-related QoL symptoms, and QoL, which were graphed. Cross-tabulation presented the distribution of GERD-HRQoL scores by their personal data and other factors using the Pearson Chi-square and exact probability tests. Results: Overall, 502 participants previously diagnosed with GERD completed the questionnaire. Participants' were aged 18-65 years (mean age of 31.5 ± 14.6 years), and 384 (76.5%) were male. The most frequent symptom affecting QoL was heartburn (85.9%), followed by postprandial heartburn (84.3%), heartburn while lying down (82.7%), bloating or gassy feelings (79.9%), and heartburn while standing up (77.3%). Conclusions: Our study showed that patients with GERD had a poor QoL due to GERD-related symptoms, mainly heartburn. Younger age, male sex, and lower educational status were associated with lower GERD-HRQoL scores.

Bilateral Wilms' Tumor With Different Responses to Preoperative Chemotherapy.

Wilms' tumor (WT) is a common type of primary renal tumor in the pediatric population that can equally affect both sides. Herein, we describe a case of bilateral Wilms' tumor (BWT) in a three-year-old male with different responses to preoperative chemotherapy in the two kidneys. The left kidney mass responded poorly to chemotherapy than the right kidney, which raised the suspicion of coexisting benign disease or congenital anomaly. However, it was ruled out by preoperative nuclear scan and ultrasound-guided frozen section biopsy taken from the left kidney mass. The report of a frozen section on hematoxylin and eosin (H&E) stain was positive for the small blue cell tumor. The patient was managed successfully with a total nephrectomy of the right kidney and nephron-sparing surgery (NSS) on the left kidney. The postoperative period was uneventful and was managed successfully with radiotherapy. Despite many challenges faced in the management of bilateral Wilms' tumor, surgery is the most preferable mode of therapy with chemotherapy and radiotherapy being effective in certain cases. The patient was followed up till no signs of recurrence or metastasis were observed.

Fibro-Osseous Lesion of the Nose and Paranasal Sinus: A Retrospective Study With Literature Review.

Background Fibro-osseous (FO) lesions are slow-growing benign lesions in the paranasal sinuses. They include osteomas, fibrous dysplasia (FD), and ossifying fibro-ma (OF). Fibro-osseous (FO) lesions are frequently asymptomatic, and they are incidentally found on imaging. They are characterized by different histological, radiological, and clinical variants. Depending on symptoms, size, location, and extension, the treatment strategy varies significantly for these lesions. Objective We aim to compare the age, onset, gender, clinical presentation, postoperative improvement, and complications of a fibro-osseous lesion in the paranasal sinuses. Methods A retrospective analysis was done targeting patients diagnosed with benign fibro-osseous (FO) lesions, and the incidence among 403 patients who underwent functional endoscopic sinus surgery (FESS) at Aseer Central Hospital, Kingdom of Saudi Arabia, was reviewed from January 2013 to January 2022. Results A total of seven patients were found; five patients were diagnosed with osteoma, and two were diagnosed with fibrous dysplasia. There were no ossifying fibroma cases. The patients' mean age was 25.5 ± 12.9 years old. Four (57.1%) patients were males, and three (42.9%) were females, with a male/female ratio of 1.25:1. The most common locations were the frontal sinus and ethmoid sinus, and the two cases of fibrous dysplasia involved almost all facial bones. The endonasal endoscopic approach was chosen to treat all seven patients. Conclusions There are differences in the onset age, location, and complications postoperatively among osteoma and fibrous dysplasia patients. Osteoma most commonly occurs in the frontal sinus, while fibrous dysplasia involved all facial bones in our study. Endoscopic surgery is currently the primary strategy for treatment.

The Hand in Distal Arthrogryposis.

Distal arthrogryposis is the second most common type of arthrogryposis after amyoplasia and is defined as arthrogryposis that affects hands and feet; it is mostly inherited in an autosomal-dominant fashion. This review discusses up-to-date background information, clinical features, and treatment of distal arthrogryposis in hands concentrating on camptodactyly, thumb-in-palm deformity, and windblown hand deformity, which are the most common and functionally limiting deformities. Treating these deformities should be individualized and follow a multidisciplinary approach. Most deformities can be initially treated nonoperatively, and if not responsive, operative treatment may be pursued to improve function. Surgery primarily aims to release soft-tissue contractures, rebalance muscle forces, and may need bony correction based on the deficits of each case. Current literature suggests that early treatment leads to better outcomes. However, reported cases are scarce, and no consensus or gold standard for treatment exists. Therefore, long-term (multicenter) studies are needed to assess outcomes and standardize the treatment of such deformities whenever possible.

Gitelman syndrome: A first published clinical association with chronic pancreatitis, a case report and review of literature.

INTRODUCTION AND IMPORTANCE: Gitelman syndrome (GS) is an autosomal recessive, salt-losing tubulopathy, also referred to as familial hypokalemia-hypomagnesemia, caused by mutation of genes encoding the sodium chloride cotransporter (NCCT) and magnesium transporters in the thiazide sensitive segments of the distal convoluted tubule (DCT) of the nephron. Patients may present with a spectrum of clinical presentations and associations. CASE PRESENTATION: Here, we report a case of a 39-year-old female with Gitelman syndrome and chronic pancreatitis in the absence of well-known causes of CP. Her clinical and radiographic profile constituted an indication for surgical intervention, namely pancreatic head and body coring and pancreaticojejunostomy (Frey's procedure) (FP). On follow up 3 month later, the patient is pain-free and is satisfied. To the best of our knowledge and based on literature review, this is the first reported case of GS with CP. CONCLUSION: The purpose of this paper is to describe a case of CP in association with established GS as a first published clinical association, raising a possibility of another possible clinical manifestation of GS. Further observational studies are encouraged to support this association.

Peroral endoscopic myotomy (POEM) for the treatment of achalasia: A multicenter Middle Eastern experience.

BACKGROUND: Peroral endoscopic myotomy (POEM) was proposed in 2010 as a minimally invasive procedure for the treatment of achalasia. In this article, we describe the Middle Eastern experience with the procedure in terms of efficacy, length of admission, and short- and long-term complications. METHODS: A retrospective analysis of our prospectively collected data on patients who underwent a POEM procedure was conducted between March 2019 and May 2020. The primary outcome was clinical success rate, defined as a postprocedure Eckardt score ≤3 at ≥3 months. Secondary outcomes included the length of hospital stay, presence of reflux symptoms or need for proton pump inhibitors (PPIs) ≥3 months, and adverse events. RESULTS: During the study period, 67 patients (35 females) underwent the procedure for achalasia. The participants' ages ranged from 11 to 80 years (mean 41 ± 18 years). Eckardt scores before the treatment ranged between 4 and 12 (mean 8.85 ± 1.75). Sixty-four patients (95.5%) achieved Eckardt scores of ≤3 at ≥3 months after the procedure (95% confidence interval [CI]: 91%-100%). The difference between pre- and post-procedural Eckardt scores averaged around -8 points (95% CI: -7.5 to -8.5 P < 0.0001). Adverse events were reported in 24 patients (35.8%) and included pneumoperitoneum (32.8%), reflux symptoms at 3 months (29.9%), and surgical emphysema (3%). Six patients had adverse events that led to prolongation of admission; 3% of whom had aspiration pneumonia, 3% had pneumoperitoneum, 1.5% had both, and 1.5% had an esophageal tear. CONCLUSIONS: POEM is a promising procedure for the treatment of achalasia with a high clinical success rate, short hospital admission, and a reassuring safety profile.

A Giant Porencephaly: A Rare Etiology of Pediatric Seizures.

Pediatric convulsive seizure is common and represents a source of major concern and anxiety for the parents. Seizures can have a broad spectrum of etiologies in children, including metabolic, traumatic, developmental, and infectious causes. Depending on the clinical presentation, laboratory testing and neuroimaging may be indicated in the workup of the first unprovoked afebrile seizure. We present a case of a six-year-old boy who was brought to the emergency department by his mother after an episode of convulsion. She reported that he had jerky repetitive movements of all extremities that lasted around two minutes with spontaneous termination. The child did not have a febrile illness. The mother reported no history of similar episodes. Upon examination, the child appeared alert and conscious. No dysmorphic features were evident. Initial laboratory investigations were within the normal limits. The child underwent magnetic resonance imaging for the brain, which demonstrated a large well-defined extra-axial cystic lesion occupying most of the left hemisphere that is connected to the ventricular system. The lesion had no grey-matter lining and it strictly followed the cerebrospinal fluid in all sequences. Such finding represented the diagnosis of a giant left porencephalic cyst. Porencephaly is an extremely rare neurological anomaly that may present with pediatric seizures. Magnetic resonance imaging is the gold standard modality for the diagnosis of porencephaly. The case demonstrated that porencephaly can have a massive size in a patient with normal psychoneurological development.

The use of direct oral anticoagulants for thromboprophylaxis or treatment of cancer-associated venous thromboembolism: a meta-analysis and review of the guidelines.

BACKGROUND: Venous thromboembolism (VTE) is a common complication among patients with cancer and is one of the most common causes of increased morbidity and mortality. The use of direct oral anticoagulants (DOACs) for thromboprophylaxis and treatment of cancer-associated venous thromboembolism (CA-VTE) has been evaluated in several randomized clinical trials (RCTs). The aim of this meta-analysis was to assess efficacy and safety of using DOACs for thromboprophylaxis and treatment of CA-VTE and provide a summary for available guidelines' recommendations. METHODS: MEDLINE was searched to identify studies evaluating the use of DOACs for thromboprophylaxis or treatment in patients with cancer. Search was limited to peer-reviewed studies published in English. Studies were excluded if they were not RCTs or subgroup analyses of data derived from RCTs, if they did not report efficacy and safety data on patients with active cancer, or if they were published as an abstract. New VTE or VTE recurrence, and major or clinically relevant non-major bleeding (CRNMB) were used to assess the efficacy and safety, respectively. The Mantel-Haenszel random-effects model risk ratios (RRs) and the corresponding 95% confidence intervals (CIs) were calculated to estimate the pooled treatment effects of DOACs. RESULTS: Four studies evaluating DOACs use for thromboprophylaxis and four - for treatment of CA-VTE were included. Thromboprophylaxis with DOACs was associated with a significant reduction in the risk of symptomatic VTE (RR = 0.58; 95%CI 0.37,0.91) but with an incremental risk of major bleeding or CRNMB (RR = 1.57; 95%CI 1.10,2.26). CA-VTE treatment with DOACs was linked with a significant reduction in VTE recurrence (RR = 0.62; 95%CI 0.44,0.87) but with an incremental risk of CRNMB (RR = 1.58; 95%CI 1.11,2.24). CONCLUSIONS: The DOACs are associated with a lower risk of symptomatic VTE and VTE recurrence, but the risk of bleeding remains a considerable concern. Clinical decisions should be made by assessing individual patient's risk of VTE and bleeding.

Neglected Neck of Femur Fracture Managed by Surgical Hip Dislocation: A Case Report and Literature Review.

INTRODUCTION: Femoral neck fractures (FNFs) in young adults are relatively uncommon emergency that requires early diagnosis and management possible to prevents joint complications. CASE REPORT: A 24-year-old male presented with a right hip pain for 3 months after a heavy physical exercise during military training. The imaging exhibited a transcervical FNF with displacement and a potential of avascular necrosis (AVN). The patient was managed by Open reduction and internal fixation through surgical hip dislocation (SHD) and bone grafting from the right iliac bone. The patient returned to his full military services 14 weeks following the surgery and was followed for 3 years without any symptomatic or functional problems. CONCLUSION: SHD could be one of the surgical options hired in the management of late presentations of FNFs in young adults with high suspicion of AVN.

Genetic, Immunological, and Clinical Features of 32 Patients with Autosomal Recessive STAT1 Deficiency.

Autosomal recessive (AR) STAT1 deficiency is a severe inborn error of immunity disrupting cellular responses to type I, II, and III IFNs, and IL-27, and conferring a predisposition to both viral and mycobacterial infections. We report the genetic, immunological, and clinical features of an international cohort of 32 patients from 20 kindreds: 24 patients with complete deficiency, and 8 patients with partial deficiency. Twenty-four patients suffered from mycobacterial disease (bacillus Calmette-Guérin = 13, environmental mycobacteria = 10, or both in 1 patient). Fifty-four severe viral episodes occurred in sixteen patients, mainly caused by Herpesviridae viruses. Attenuated live measles, mumps, and rubella and/or varicella zoster virus vaccines triggered severe reactions in the five patients with complete deficiency who were vaccinated. Seven patients developed features of hemophagocytic syndrome. Twenty-one patients died, and death was almost twice as likely in patients with complete STAT1 deficiency than in those with partial STAT1 deficiency. All but one of the eight survivors with AR complete deficiency underwent hematopoietic stem cell transplantation. Overall survival after hematopoietic stem cell transplantation was 64%. A diagnosis of AR STAT1 deficiency should be considered in children with mycobacterial and/or viral infectious diseases. It is important to distinguish between complete and partial forms of AR STAT1 deficiency, as their clinical outcome and management differ significantly.

Recurrent Mixed Neuroendocrine-Non-Neuroendocrine Neoplasm in the Gallbladder: A Case Report.

Mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) of the gallbladder are rare with no established therapeutic strategies. We report a case of recurrent gallbladder MiNEN from a population with a low incidence of gallbladder carcinomas, a review of the current therapeutic options, and recent updates on the nomenclature proposed by the World Health Organization in 2017.

Aggressive L3 vertebral hemangioma coexisting with adult thoracolumbar scoliosis: Case report.

Vertebral hemangiomas are benign vascular tumors that are commonly asymptomatic. A low percentage might become aggressive; however, they are not known to be associated with scoliosis. We present a case of a third lumbar vertebral lesion coexisting with a moderate thoracolumbar scoliosis. The patient's initial presentation was back pain with bilateral lower limb radiculopathy and neurogenic claudication. Diagnosis was established using CT and MRI, which showed classical findings of an aggressive vertebral hemangioma. The patient underwent Partial hemangioma excision and scoliosis correction, with satisfactory outcome at 1 year follow up.