Epidemiological observations and management challenges in extrapedal mycetoma: A three-decade review of 420 cases.

Mycetoma is a serious, destructive, disfiguring chronic granulomatous inflammatory disease affecting the subcutaneous tissues that spread to involve the skin, deep tissues and bone. The disease predominately affects the limbs, and extrapedal mycetoma is rarely reported. The reported extrapedal ones are characterised by high morbidity and mortality. This communication reports on 420 patients with extrapedal mycetoma seen and managed at the Mycetoma Research Centre (MRC), University of Khartoum, between January 1991 and December 2021. In this descriptive, cross-sectional, hospital-based study, the electronic records of all mycetoma-confirmed patients seen during the study period were carefully and meticulously reviewed. The confirmed patients with extrapedal mycetoma were included in this study. The study included 420 patients with extrapedal mycetoma, 298 (70.7%) had eumycetoma, and 122 (29.3%) had actinomycetoma. There were 343 male patients (81.7%) and 77 (18.3%) females, with a male-to-female ratio of 4:1. Their ages ranged between 1.5 and 95 years, with a median of 28 years. Most of the patients were students and farmers. The majority of patients were from El Gezira, North Kordofan, and the White Nile States. Mycetoma was painful in 21%, and a family history of mycetoma was recorded in 11.5% of patients. The buttocks (37.9%) and head and neck (16.9%) were affected most. Less frequently affected sites were the trunk and back (12%) each, abdominal and chest walls (4.5%) each and loin (1%). The prominent clinical presentation findings were multiple sinuses discharging grains (55%), massive swellings (46%), and lymphadenopathy (11.5%). Less commonly observed clinical findings were local hyperhidrosis (5.3%) and dilated tortuous veins close to mycetoma lesions (0.5%). The study showed that 204 patients (48.6%) had clinical improvement in terms of decreased lesion size and healing of sinuses following medical therapy. Sixty-six patients (15.7%) had no noticeable improvement. The lesion continued progressing despite treatment in 44 patients (10.5%). In the study, 118 patients were on regular follow-up, and in this group, a cure was documented in 25 patients (21.1%) with eumycetoma and 23 (19.4%) with actinomycetoma. Post-operative recurrence among eumycetoma patients was 40%, with a 1% mortality rate. The treatment outcome was unsatisfactory, characterised by a low cure rate, high recurrence (40%) and follow-up dropout (57%) rates. This emphasises the importance of early case detection and management, objective health education programmes and thorough patient counselling to urge people to seek treatment early and reduce dropouts.

Therapeutic advances in obesity management: an overview of the therapeutic interventions.

Obesity has become a global epidemic in the modern world, significantly impacting the global healthcare economy. Lifestyle interventions remain the primary approach to managing obesity, with medical therapy considered a secondary option, often used in conjunction with lifestyle modifications. In recent years, there has been a proliferation of newer therapeutic agents, revolutionizing the treatment landscape for obesity. Notably, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), such as semaglutide, liraglutide, and the recently approved dual GLP-1/GIP RAs agonist tirzepatide, have emerged as effective medications for managing obesity, resulting in significant weight loss. These agents not only promote weight reduction but also improve metabolic parameters, including lipid profiles, glucose levels, and central adiposity. On the other hand, bariatric surgery has demonstrated superior efficacy in achieving weight reduction and addressing overall metabolic imbalances. However, with ongoing technological advancements, there is an ongoing debate regarding whether personalized medicine, targeting specific components, will shape the future of developing novel therapeutic agents for obesity management.

The Effect of Thiazolidinediones in Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a complex endocrine condition affecting women of reproductive age. It is characterised by insulin resistance and is a risk for type 2 diabetes mellitus (T2DM). The aim of this study was to review the literature on the effect of pioglitazone and rosiglitazone in women with PCOS. METHODS: We searched PubMed, MEDLINE, Scopus, Embase, Cochrane Library and the Web of Science in April 2020 and updated in March 2023. Studies were deemed eligible if they were randomised controlled trials (RCTs) reporting the effect of pioglitazone and rosiglitazone in PCOS. The study follows the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Two reviewers independently extracted data and assessed the risk of bias using the Cochrane risk of bias tool. RESULTS: Out of 814 initially retrieved citations, 24 randomised clinical trials (RCTs) involving 976 participants were deemed eligible. Among women with PCOS, treatment with rosiglitazone compared to metformin resulted in a significant increase in the mean body weight (mean difference (MD) 1.95 kg; 95% CI 0.03-3.87, p = 0.05). Metformin treatment was associated with a reduction in mean body mass index (BMI) compared to pioglitazone (MD 0.85 kg/m2; 95% CI 0.13-1.57, p = 0.02). Both pioglitazone compared to placebo (MD 2.56 kg/m2; 95% CI 1.77-3.34, p < 0.00001) and rosiglitazone compared to metformin (MD 0.74 kg/m2; 95% CI 0.07-1.41, p = 0.03) were associated with a significant increase in BMI. Treatment with pioglitazone compared to placebo showed a significant reduction in triglycerides (MD - 0.20 mmol/L; 95% CI - 0.38 to - 0.03, p = 0.02) and fasting insulin levels (MD - 11.47 mmol/L; 95% CI - 20.20, - 2.27, p = 0.01). Rosiglitazone compared to metformin was marginally significantly associated with a reduction in the luteinising hormone (LH) (MD - 0.62; 95% CI - 1.25-0.00, p = 0.05). CONCLUSION: Both pioglitazone and rosiglitazone were associated with significant increases in body weight and BMI when compared with metformin or placebo. Pioglitazone significantly reduced triglycerides and fasting insulin when compared with placebo while rosiglitazone showed a modest reduction of LH when compared with metformin. PROSPERO REGISTRATION NO: CRD42020178783.

An ingestible self-propelling device for intestinal reanimation.

Postoperative ileus (POI) is the leading cause of prolonged hospital stay after abdominal surgery and is characterized by a functional paralysis of the digestive tract, leading to symptoms such as constipation, vomiting, and functional obstruction. Current treatments are mainly supportive and inefficacious and yield acute side effects. Although electrical stimulation studies have demonstrated encouraging pacing and entraining of the intestinal slow waves, no devices exist today to enable targeted intestinal reanimation. Here, we developed an ingestible self-propelling device for intestinal reanimation (INSPIRE) capable of restoring peristalsis through luminal electrical stimulation. Optimizing mechanical, material, and electrical design parameters, we validated optimal deployment, intestinal electrical luminal contact, self-propelling capability, safety, and degradation of the device in ex vivo and in vivo swine models. We compared the INSPIRE's effect on motility in models of normal and depressed motility and chemically induced ileus. Intestinal contraction improved by 44% in anesthetized animals and up to 140% in chemically induced ileus cases. In addition, passage time decreased from, on average, 8.6 days in controls to 2.5 days with the INSPIRE device, demonstrating significant improvement in motility. Luminal electrical stimulation of the intestine via the INSPIRE efficaciously restored peristaltic activity. This noninvasive option offers a promising solution for the treatment of ileus and other motility disorders.

Vesical ectopic pregnancy due to vesicouterine fistula: A case report with literature review.

This case report describes the presentation, diagnosis, and surgical management of a rare vesical ectopic pregnancy in a 36-year-old woman with a history of multiple cesarean sections. The patient presented with symptoms of suprapubic pain, fever, and amenorrhea. An initial ultrasound indicated retained products of conception, leading to a preliminary diagnosis of septic miscarriage. However, subsequent rescanning revealed an empty uterus and a non-viable fetus within the bladder, connected to the uterine cavity. Cystoscopy confirmed the presence of fetal parts inside the bladder. Finally, a laparotomy was performed and the fetus was removed from the bladder with repair of the underlying uterovesical fistula. An uneventful postoperative period ensued. The literature review revealed only four previously reported cases with similar overall presentations. This case highlights the importance of considering vesical ectopic pregnancies in patients with a history of cesarean sections and unusual symptoms, as prompt surgical intervention is crucial for ensuring successful management of the condition.

Nucleotide-free structures of KIF20A illuminate atypical mechanochemistry in this kinesin-6.

KIF20A is a critical kinesin for cell division and a promising anti-cancer drug target. The mechanisms underlying its cellular roles remain elusive. Interestingly, unusual coupling between the nucleotide- and microtubule-binding sites of this kinesin-6 has been reported, but little is known about how its divergent sequence leads to atypical motility properties. We present here the first high-resolution structure of its motor domain that delineates the highly unusual structural features of this motor, including a long L6 insertion that integrates into the core of the motor domain and that drastically affects allostery and ATPase activity. Together with the high-resolution cryo-electron microscopy microtubule-bound KIF20A structure that reveals the microtubule-binding interface, we dissect the peculiarities of the KIF20A sequence that influence its mechanochemistry, leading to low motility compared to other kinesins. Structural and functional insights from the KIF20A pre-power stroke conformation highlight the role of extended insertions in shaping the motor's mechanochemical cycle. Essential for force production and processivity is the length of the neck linker in kinesins. We highlight here the role of the sequence preceding the neck linker in controlling its backward docking and show that a neck linker four times longer than that in kinesin-1 is required for the activity of this motor.

Microbiome diversity in African American, European American, and Egyptian colorectal cancer patients.

Purpose: Although there is an established role for microbiome dysbiosis in the pathobiology of colorectal cancer (CRC), CRC patients of various race/ethnicities demonstrate distinct clinical behaviors. Thus, we investigated microbiome dysbiosis in Egyptian, African American (AA), and European American (EA) CRC patients. Patients and methods: CRCs and their corresponding normal tissues from Egyptian (n = 17) patients of the Alexandria University Hospital, Egypt, and tissues from AA (n = 18) and EA (n = 19) patients at the University of Alabama at Birmingham were collected. DNA was isolated from frozen tissues, and the microbiome composition was analyzed by 16S rRNA sequencing. Differential microbial abundance, diversity, and metabolic pathways were identified using linear discriminant analysis (LDA) effect size analyses. Additionally, we compared these profiles with our previously published microbiome data derived from Kenyan CRC patients. Results: Differential microbiome analysis of CRCs across all racial/ethnic groups showed dysbiosis. There were high abundances of Herbaspirillum and Staphylococcus in CRCs of Egyptians, Leptotrichia in CRCs of AAs, Flexspiria and Streptococcus in CRCs of EAs, and Akkermansia muciniphila and Prevotella nigrescens in CRCs of Kenyans (LDA score >4, adj. p-value <0.05). Functional analyses showed distinct microbial metabolic pathways in CRCs compared to normal tissues within the racial/ethnic groups. Egyptian CRCs, compared to normal tissues, showed lower l-methionine biosynthesis and higher galactose degradation pathways. Conclusions: Our findings showed altered mucosa-associated microbiome profiles of CRCs and their metabolic pathways across racial/ethnic groups. These findings provide a basis for future studies to link racial/ethnic microbiome differences with distinct clinical behaviors in CRC.

Epidemiological, Clinical, and Histopathological Features of Salivary Gland Tumors among 150 Sudanese Patients: 10 Years' Experience.

Background and Objectives: Salivary gland tumors (SGTs) are serious challenges to pathologists. Herein, we aimed to assess epidemiological and histopathological characteristics of SGTs among Sudanese patients. Materials and Methods: This retrospective descriptive study was undertaken at The pathology department in Khartoum State between 2008 and 2018. Patient records, histopathological reports, and slides were retrieved; and re-examined by two histopathologists. Diagnoses were reclassified according to the 2017 WHO classification of SGTs. Results: Overall, 150 cases of Sudanese patients with SGT were included (90 [60%] males and 60 [40%] females). Among these, 105 were benign (70%) and 45 were malignant (30%). The parotid glands were the most common site for both benign and malignant tumors (77/150; 51%: 59 benign (76.6%) and 18 malignant [23.4%]). The next common site was the submandibular gland (54 [36%]: 38 benign [70.3%] and 16 malignant [29.7%]), followed by minor salivary glands (19 [12.7%]: 8 benign and 11 malignant [57.9%]). Benign gland entities included pleomorphic adenoma (88/105; 83.7%), oncocytoma (5/105; 4.8%), myoepithelioma (4/105; 3.8%), Whartin tumors (3/105; 2.9%), basal cell adenoma (3/105; 2.9%), and sialolipoma (2/105; 1.9%). Malignant gland entities included adenoid cystic carcinoma (12; 26.7%), mucoepidermoid carcinoma (10; 22,2%), acinic cell carcinoma (6; 13.3%), poorly differentiated carcinoma (4; 8.9%), adenocarcinoma NOS (not otherwise specified) (4; 8.9%), basal cell adenocarcinoma (3; 6.7%), carcinoma ex pleomorphic adenoma (3; 6.7%), polymorphous adenocarcinoma (2; 4.4%), salivary duct carcinoma (1; 2.2%), and epithelial-myoepithelial carcinoma (2.2%). Conclusions: SGTs shared several epidemiological and histopathological features, exhibiting high incidence in the parotid and submandibular glands, lower prevalence in minor glands, and greater male predominance.

Antioxidant activity and total phenolic compounds of Commiphora gileadensis extracts obtained by ultrasonic-assisted extraction, with monitoring antiaging and cytotoxicity activities.

Commiphora gileadensis (C. gileadensis) has been identified and linked with various health benefits and pharmaceutical potential for its phytochemical activities and chemical constituents. This study aimed to evaluate ultrasonic-assisted extraction (USE) technique for total phenols content from C. gileadensis leaf compared to the hydrodistillation extraction (HDE). Our results showed that the USE operating conditions were identified as: MeOH·H2O solvent-to-fresh sample ratio of 80:20 (v/v); ultrasonic power/frequency at 150 W/20 kHz; and a temperature of 40 ± 1°C; subjected to acoustic waves intermittently for a calculated time (5 min) during the total programmed time of 12 min. The USE exhibited (118.71 ± 0.009 mg GAE/g DM) more amounts of all phenols than HDE (101.47 ± 0.005 mg GAE/g DM), and antioxidant (77.78 ± 0.73%, 75.27 ± 0.59% scavenging inhibition of DPPH), respectively. Anti-aging and Cytotoxicity activities were investigated. The results of biological evaluations showed that the crude extracts of C. gileadensis significantly extended the replicative lifespan of K6001 yeast. In addition, in vitro cytotoxicity against the HepG2 cell line showed significant anticancer activity, and approximately 100 µg/mL is required to decrease viability compared with that of the control. This study is proven for a larger scale to extract and isolate compounds of C. gileadensis for potential utilization in the pharmaceutical industry. In conclusion, advanced methods afford an extract with high activity in the biological properties of the extract.

A Case Series of Non-Tuberculous Mycobacterial Pulmonary Disease Masquerading as Malignancy From a Community-Based Hospital.

Non-tuberculous mycobacteria (NTM) are ubiquitous organisms in the environment that can potentially cause a range of pulmonary and extrapulmonary infections in humans. Epidemiological risk factors and the host's immune status determine the susceptibility to various clinical syndromes caused by different NTM species. Non-tuberculous mycobacteria pulmonary disease (NTM-PD) is primarily reported in patients with underlying lung disease. These infections often pose a significant disease burden on affected patients as they are often chronic, difficult to treat, and necessitate long-term multi-drug therapy. Mycobacterium avium complex (MAC) is the most common causative pathogen of NTM-PD in the USA, followed by Mycobacterium kansasii (M. kansasii). Less common species in the USA include Mycobacterium xenopi (M. xenopi), Mycobacterium abscessus, and others, largely depending upon the geographic location and exposure to species-specific predisposing risks. In this case series, the authors report on three elderly patients with chronic lung diseases who had pulmonary NTM disease caused by M. xenopi and MAC. The patients were encountered in both inpatient and outpatient settings from a community-based hospital in the midwestern USA. The clinical and radiological features of NTM-PD masqueraded as malignancy and posed a diagnostic dilemma. The epidemiology, clinical and radiological features, diagnosis, and management of NTM-PD are reviewed in this report.

Metastatic Squamous Cell Carcinoma From Primary Hypopharynx Source to Gastric Mucosa Presenting as Massive Gastrointestinal Bleeding.

Percutaneous endoscopic gastrostomy (PEG) is a relatively safe procedure that represents an important supportive adjunctive component for patients with primary head and neck squamous cell carcinoma (HNSCC). The HNSCC population is considered a high-risk group for developing critical nutritional deficiency due to a multitude of factors. Nevertheless, as the use of PEG in modern practice is gaining more popularity due to various indications, unusual complications have been increasingly reported. PEG site metastasis from primary HNSCC has emerged as a rare, yet serious oncological phenomenon that warrants careful consideration. The authors report an unusual case of squamous cell carcinoma (SCC) of the hypopharynx that metastasized to the gastric body mucosa through a PEG site. The metastatic SCC presented as massive gastrointestinal bleeding, and esophagogastroscopy revealed an ulcerated mass in the gastric body masquerading as a primary gastric adenocarcinoma. Histopathology and immunohistochemistry examination confirmed metastatic SCC which concurred with the patient's primary hypopharyngeal SCC. The review of the updated literature revealed that a total of 121 cases of this rare oncological entity have been reported to date. Physicians need to be vigilant of the symptoms of PEG site metastasis to accurately diagnose and manage the care of this rare occurrence as it is associated with poor prognosis.

Statin-Induced Immune-Mediated Necrotizing Myopathy Resulting in Proximal Muscle Weakness.

Statin-induced immune-mediated necrotizing myopathy (IMNM) is a subtype of IMNM linked to exposure to statins and is characterized by positive anti-hydroxymethylglutaryl (HMG) coenzyme A reductase (HMGCR) antibodies. Although rare, this entity has become increasingly recognized as a cause of proximal muscle weakness, especially with the widespread use of statin therapy. Unlike typical statin-associated muscle symptoms, IMNM myopathy often causes severe muscle injury, and muscle weakness persists or sometimes worsens following the withdrawal of statin therapy. Medical practitioners need to keep a high index of clinical suspicion for statin-induced IMNM in patients taking statins who present with muscle weakness. The disease can be debilitating, and treatment strategies are not well established despite the advances that have been made in the diagnosis. Here we present the clinical characteristics and disease course of two cases of statin-induced IMNM. Both patients presented with progressive proximal muscle weakness and myalgias while on long-term statin therapy without significant improvement in their symptoms following the withdrawal of statin therapy. IMNM was suspected, and both patients were found to have high titers of anti-HMG coenzyme A reductase antibodies and demonstrated microscopic features consistent with a diagnosis of IMNM on muscle biopsy. The patients experienced significant disability due to muscle weakness and required a protracted course of escalated immunosuppressive therapy. Although rare, IMNM should be suspected in patients taking statins who present with muscle weakness that fails to improve or worsens when statins were stopped. Early diagnosis and institution of immunosuppressive therapy are important to prevent the progression of the disease.

Polycystic ovarian syndrome among women diagnosed with infertility in the Gulf Cooperation Council countries: A protocol for systematic review and meta-analysis of prevalence studies.

BACKGROUND: Polycystic ovarian syndrome, a common endocrine disorder, is an important cause of infertility among women of reproductive age. Within the Gulf Cooperation Council countries, polycystic ovarian syndrome is found to affect women increasingly. No study has been carried out to critically summarize the evidence on the prevalence of polycystic ovarian syndrome among women suffering from infertility in these countries. OBJECTIVE: This protocol aims to conduct a systematic review and meta-analysis of the studies reporting the prevalence of polycystic ovarian syndrome among women seeking infertility treatment in the six Gulf Cooperation Council countries (Bahrain, Kuwait, Oman, Saudi Arabia, Qatar, and United Arab Emirates). DESIGN/METHODS AND ANALYSIS: The systematic review and meta-analysis will follow the following method. DATA SOURCE: Five databases, including PubMed, Embase, CINAHL, Web of Science, and SCOPUS, will be searched for observational studies using a combination of relevant keywords and Medical Subject Headings from inception of databases. DATA EXTRACTION: Two reviewers will screen titles and abstracts, followed by a full-text search based on the eligibility criteria. The main outcome is to measure the proportion of women who have polycystic ovarian syndrome among infertility-diagnosed patients. In addition, the risk of bias in the included studies will be assessed using the national institute of health quality assessment tool for observational studies. DATA SYNTHESIS: The random-effects method of the analysis with the inverse variance will be used to calculate the pooled prevalence of polycystic ovarian syndrome-attributed infertility. Variation in prevalence estimates will be calculated using subgroup analysis based on study and patients' characteristics and publication bias will be assessed via funnel plot inspection and Eggar's test. DISCUSSION: A critical assessment of evidence on the prevalence of polycystic ovarian syndrome in women attending fertility clinics is helpful in risk quantification, enabling better planning for managing infertility in women with polycystic ovarian syndrome. REGISTRATION: This protocol has been registered with PROSPERO, protocol registration number (CRD42022355087).

Real-world utility of a genomic classifier in establishing a diagnosis of newly identified interstitial lung disease.

BACKGROUND: Diagnosing interstitial lung disease (ILD) remains challenging. Guidelines recommend utilizing a multidisciplinary discussion (MDD) to review clinical and radiographic data and if diagnostic uncertainty persists, then to obtain histopathology. Surgical lung biopsy and transbronchial lung cryobiopsy (TBLC) are acceptable methods, but risks of complications may be prohibitive. The Envisia genomic classifier (EGC) represents another option to determine a molecular usual interstitial pneumonia (UIP) signature to facilitate an ILD diagnosis at MDD with high sensitivity and specificity. We evaluated the concordance between TBLC and EGC at MDD and the safety of this procedure. METHODS: Demographic data, pulmonary function values, chest imaging pattern, procedural information, and MDD diagnosis were recorded. Concordance was defined as agreement between the molecular EGC results and histopathology from TBLC in the context of the patient's High Resolution CT pattern. RESULTS: 49 patients were enrolled. Imaging demonstrated a probable (n = 14) or indeterminate (n = 7) UIP pattern in 43% and an alternative pattern in 57% (n = 28). EGC results were positive for UIP in 37% (n = 18) and negative in 63% (n = 31). MDD diagnosis was obtained in 94% (n = 46) with fibrotic hypersensitivity pneumonitis (n = 17, 35%) and IPF (n = 13, 27%) most common. The concordance between EGC and TBLC at MDD was 76% (37/49) with discordant results seen in 24% (12/49) of patients. CONCLUSIONS: There appears to be reasonable concordance between EGC and TBLC results at MDD. Efforts clarifying the contributions of these tools to an ILD diagnosis may help identify specific patient populations that may benefit from a tailored diagnostic approach.

A Rare Case of Granulomatous Mastitis Associated With Positive Systemic Lupus Erythematosus Serology in a Young Female Patient: A Case Report and Literature Review.

Granulomatous mastitis (GM) is a rare benign breast disease that affects women of childbearing age, usually within five years of pregnancy. The hallmark diagnostic feature of GM is the presence of lobular granulomatous inflammation. The occurrence of this clinicopathological entity is usually idiopathic. Nevertheless, GM has often been associated with systemic inflammatory conditions of either infectious (such as tuberculosis) or autoimmune etiology (particularly sarcoidosis, vasculitis, and less likely systemic lupus erythematosus [SLE]). In this report, the authors described an unusual case of GM that was associated with features of SLE in a young female patient who presented with a painful breast lump. Histopathological examination of the lump's biopsy showed GM. Further laboratory workup revealed evidence of some immunological criteria of SLE. Steroid therapy led to the resolution of the patient's breast swelling. The breast mass remained in remission with hydroxychloroquine treatment. Only a handful of similar cases in the current literature demonstrated a plausible association between SLE and GM. Our case provides a reference to consider SLE as a possible differential diagnosis when GM is encountered in young-aged female patients.

Impact of pharmacological interventions on biochemical hyperandrogenemia in women with polycystic ovary syndrome: a systematic review and meta-analysis of randomised controlled trials.

CONTEXT: Polycystic ovary syndrome (PCOS) is a complex endocrine disease that affects women of reproductive age and is characterised by biochemical and clinical androgen excess. AIM: To evaluate the efficacy of pharmacological interventions used to decrease androgen hormones in women with PCOS. DATA SOURCE: We searched PubMed, MEDLINE, Scopus, Embase, Cochrane library and the Web of Science from inception up to March 2021. DATA SYNTHESIS: Two reviewers selected eligible studies and extracted data, and the review is reported according to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). RESULTS: Of the 814 randomised clinical trials (RCTs) located in the search, 92 met the eligibility criteria. There were significant reductions in total testosterone level with metformin versus (vs) placebo (SMD: - 0.33; 95% CI  - 0.49 to  - 0.17, p < 0.0001, moderate grade evidence) and dexamethasone vs placebo (MD:-0.86 nmol/L; 95% CI  - 1.34 to  - 0.39, p = 0.0004, very low-grade evidence). Significant reductions in the free testosterone with sitagliptin vs placebo (SMD:  - 0.47; 95% CI  - 0.97 to 0.04, p = 0.07, very low-grade evidence), in dehydroepiandrosterone sulphate (DHEAS) with flutamide vs finasteride (MD:  - 0.37 µg/dL; 95% CI  - 0.05 to  - 0.58, p = 0.02, very low-grade evidence), a significant reduction in androstenedione (A4) with rosiglitazone vs placebo (SMD:  - 1.67; 95% CI  - 2.27 to  - 1.06; 59 participants, p < 0.00001, very low-grade evidence), and a significant increase in sex hormone-binding globulin (SHBG) with oral contraceptive pill (OCP) (35 µg Ethinyl Estradiol (EE)/2 mg cyproterone acetate (CPA)) vs placebo (MD: 103.30 nmol/L; 95% CI 55.54-151.05, p < 0.0001, very low-grade evidence) were observed. CONCLUSION: Metformin, OCP, dexamethasone, flutamide, and rosiglitazone use were associated with a significant reduction in biochemical hyperandrogenemia in women with PCOS, though their individual use may be limited due to their side effects. PROSPERO REGISTRATION NO: CRD42020178783.

Nephrogenic Ascites: An Unusual Culprit of Refractory Ascites in a Hemodialysis Patient-A Case Report and Review of Literature.

Nephrogenic ascites or dialysis-associated ascites is a rare condition that develops in patients with end-stage renal disease (ESRD) who have been on long-term hemodialysis. It is characterized by rapidly accumulating ascites that is often recurrent and resistant to standard treatment. The diagnosis typically requires the exclusion of common causes of ascites including possible hepatic, cardiac, malignant, and infectious etiologies. Nephrogenic ascites generally has a poor prognosis. Renal transplantation is the sole definitive cure for this difficult-to-treat clinical entity, however, majority of the affected patients are usually deemed unsuitable candidates for transplantation. In this communication, the authors presented a rare case of nephrogenic ascites that posed a therapeutic challenge in an ESRD patient on regular hemodialysis along with a brief review of the literature regarding the pathogenesis, clinical features, and outcome of nephrogenic ascites.

A signature of Prevotella copri and Faecalibacterium prausnitzii depletion, and a link with bacterial glutamate degradation in the Kenyan colorectal cancer patients.

Background: Colorectal cancer (CRC) is the fifth most diagnosed cancer in Sub-Saharan Africa. In Kenya, CRC incidence rates tripled from 1997 to 2017. In the Moi Teaching and Referral Hospital, Moi University, there has been an increase in CRC cases, notably for younger patients. A suggested pathobiology for this increase is gut microbiome dysbiosis. Since, for the Kenyan CRC patient population, microbiome studies are rare, there is a need for a better understanding of how microbiome dysbiosis influences CRC epidemiology in Kenya. In this single-center study, the focus was on profiling the gut microbiome of Kenyan CRC patients and healthy volunteers and evaluating associations between microbiome profiles and the age of CRC patients. Methods: The gut mucosa-associated microbiome of 18 CRC patients and 18 healthy controls were determined by 16S rRNA sequencing and analyzed for alpha and beta diversity, differential abundance, and microbial metabolic profiling. Results: Alpha diversity metrics showed no significant differences, but beta diversity metrics showed dissimilarities in the microbial communities between CRC patients and healthy controls. The most underrepresented species in the CRC group were Prevotella copri (P. copri) and Faecalibacterium prausnitzii (F. prausnitzii), although Bacteroides fragilis (B. fragilis) and Prevotella nigrescens were overrepresented (linear discriminant analysis, LDA score >2, P<0.05). Also, for CRC patients, significant metagenomic functional alterations were evident in microbial glutamate metabolic pathways (L-glutamate degradation VIII was enriched, and L-glutamate and L-glutamine biosynthesis were diminished) (P<0.05, log2 Fold Change >1). Moreover, the microbiome composition was different for patients under 40 years of age compared to older patients (LDA score >2, P<0.05). Conclusions: Microbiome and microbial metabolic profiles of CRC patients are different from those of healthy individuals. CRC microbiome dysbiosis, particularly P. copri and F. prausnitzii depletion and glutamate metabolic alterations, are evident in Kenyan CRC patients.

RoboCap: Robotic mucus-clearing capsule for enhanced drug delivery in the gastrointestinal tract.

Oral drug delivery of proteins is limited by the degradative environment of the gastrointestinal tract and poor absorption, requiring parenteral administration of these drugs. Luminal mucus represents the initial steric and dynamic barrier to absorption. To overcome this barrier, we report the development of the RoboCap, an orally ingestible, robotic drug delivery capsule that locally clears the mucus layer, enhances luminal mixing, and topically deposits the drug payload in the small intestine to enhance drug absorption. RoboCap's mucus-clearing and churning movements are facilitated by an internal motor and by surface features that interact with small intestinal plicae circulares, villi, and mucus. Vancomycin (1.4 kilodaltons of glycopeptide) and insulin (5.8 kilodaltons of peptide) delivery mediated by RoboCap resulted in enhanced bioavailability 20- to 40-fold greater in ex vivo and in vivo swine models when compared with standard oral delivery (P < 0.05). Further, insulin delivery via the RoboCap resulted in therapeutic hypoglycemia, supporting its potential to facilitate oral delivery of drugs that are normally precluded by absorption limitations.

The outcome of rituximab in treating steroid dependent nephrotic syndrome.: Histopathology and immunosuppressive drugs as predicting factors.

OBJECTIVES: To present our experience of treating steroid-dependent nephrotic syndrome (SDNS) in children with repeated doses of rituximab (RTX) with a relatively long follow-up, and to discuss the role of the histopathology type and previous immune-suppressor (IS) drugs on the outcome of these patients. METHODS: The patients included in this prospective study were children with SDNS who were in remission on a high-dose steroid or with additional IS drugs. All patients underwent renal biopsy before RTX treatment. Intravenous RTX was administered monthly at 375 mg/m2 for 4 doses. Response to treatment was defined as maintaining remission with no steroid-sparing agents or prednisone for one year. RESULTS: Seventeen (14 males) patients were enrolled. Approximately 76% had minimal change disease (MCD) and 3 (18%) patients had immunoglobulin M (IgM) nephropathy. Approximately 85% of MCD and 33% of IgM nephropathy showed complete response to RTX. CONCLUSION: Compared to other IS used to treat SDNS, RTX showed a significant decrease in relapse rate with fewer side effects. The dose and interval should be modified according to the patient's characteristics, such as medical history, pathology type, and previous IS agents.