Exploring novel microbial metabolites and drugs for inhibiting Clostridioides difficile.

Clostridioides difficile is an enteric pathogen that can cause a range of illnesses from mild diarrhea to pseudomembranous colitis and even death. This pathogen often takes advantage of microbial dysbiosis provoked by antibiotic use. With the increasing incidence and severity of infections, coupled with high recurrence rates, there is an urgent need to identify innovative therapies that can preserve the healthy state of the gut microbiota. In this study, we screened a microbial metabolite library against C. difficile. From a collection of 527 metabolites, we identified 18 compounds with no previously identified antimicrobial activity and metabolites that exhibited potent activity against C. difficile growth. Of these 18 hits, five drugs and three metabolites displayed the most potent anti-C. difficile activity and were subsequently assessed against 20 clinical isolates of C. difficile. These potent agents included ecteinascidin 770 (minimum inhibitory concentration against 50% of isolates [MIC50] ≤0.06 µg/mL); 8-hydroxyquinoline derivatives, such as broxyquinoline and choloroquinaldol (MIC50 = 0.125 µg/mL); ionomycin calcium salt, carbadox, and robenidine hydrochloride (MIC50 = 1 µg/mL); and dronedarone and milbemycin oxime (MIC50 = 4 µg/mL). Unlike vancomycin and fidaxomicin, which are the standard-of-care anti-C. difficile antibiotics, most of these metabolites showed robust bactericidal activity within 2-8 h with minimal impact on the growth of representative members of the normal gut microbiota. These results suggest that the drugs and microbial metabolite scaffolds may offer alternative avenues to address unmet needs in C. difficile disease prevention and treatment. IMPORTANCE: The most frequent infection associated with hospital settings is Clostridioides difficile, which can cause fatal diarrhea and severe colitis, toxic megacolon, sepsis, and leaky gut. Those who have taken antibiotics for other illnesses that affect the gut's healthy microbiota are more susceptible to C. difficile infection (CDI). Recently, some reports showed higher recurrence rates and resistance to anti-C. difficile, which may compromise the efficacy of CDI treatment. Our study is significant because it is anticipated to discover novel microbial metabolites and drugs with microbial origins that are safe for the intestinal flora, effective against C. difficile, and reduce the risk of recurrence associated with CDI.

Prostate cancer among Saudis: a registry review.

Background: Policy makers in Saudi Arabia greatly rely on published studies to make major public health decisions. Prostate cancer (PCa) studies in Saudi Arabia are either outdated or limited to local regions. Aim: The authors aim to analyze the Saudi Cancer Registry to determine the incidence of PCa across all regions of the Kingdom and the risk factors of poor prognosis in the population. Methods: Patients diagnosed with primary PCa from 1 January 2008 to 31 December 2017 were included in the study from the Saudi Cancer Registry. Incidence rates and risk factors for poor survival were calculated. Results: A total of 3607 PCa patients were retrieved. PCa incidence rates ranged from 0.2 to 1.4 per 100 000. Most of the patients were aged 60 and older (86.5%; n=3120), married (97%; n=3497) and lived in the central region (38.1%; n=1375). The mean age at diagnosis was 71.1 (10.8) years. Over half of all tumors were poorly differentiated (64.2%; n=2317), and localized (60.4%; n=2180). The all-time metastasis rate reached 31.4% (n=1131). The lowest mean survival was in those with distant metastasis (P=0.039). Age groups, marital status, tumor morphology, place of residency, and grade were not proven to significantly influence survival. Conclusion: The high metastasis rate and evidence of a greater incidence of newly diagnosed metastatic PCa indicate that the idea of select screening for certain high-risk populations is not farfetched. The authors encourage the promotion of awareness regarding PCa risk factors and screening to optimize prognosis and minimize late presentations and high metastasis rates.

Giant staghorn stone causing inferior vena cava compression: a novel case report.

Staghorn calculi (SC) are defined as large kidney stones that fill the renal pelvis and at least one renal calyx. They represent 10-20% of all renal stones in developing countries and require prompt diagnosis and management. Massive SC (over 5 cm) are treated exclusively via open surgery, despite percutaneous nephrolithotomy (PCNL) being the gold standard treatment for large stones. Descriptions of PCNL for massive SC are very limited in the literature. Case Presentation: We report a case of a 63-year-old male who presented with chronic abdominal pain, hepatosplenomegaly, and normal renal function. He was later diagnosed with polycythemia vera. Computed tomography of the abdomen revealed massive, bilateral staghorn stones measuring 7.3×5.5 cm and 1.8×4.5 cm on the right and left, respectively. Additionally, the right stone was found to be compressing the inferior vena cava (IVC). The patient was promptly scheduled for right-sided PCNL and the target of 80% stone fragmentation was successfully attained. Discussion: We present the first case of a stone of such size in the Middle East, as well as the first known case of a renal stone compressing the IVC. Unlike previous reports, the stone was successfully fragmented via PCNL - a procedure that has not been described for stones of such size. Conclusion: This report highlights that ultrasound-guided PNCL without any other intervention is sufficient for the successful treatment of giant SC. Greater research is needed on the potential utility of using ultrasound-guided PCNL for the fragmentation of stones sized over 5 cm.

The association of genitourinary cancer among Saudi patients with gastrointestinal stromal tumors and a systematic literature review.

The gastrointestinal tract's most commonly occurring primary mesenchymal tumor is the gastrointestinal stromal tumor (GIST). However, few cases worldwide were reported associated with renal cell carcinoma (RCC). Therefore, we aimed to identify the association of genitourinary tumors in patients with GIST in our tertiary care hospital in Saudi Arabia and compare it to the literature. We identified all patients in the pathology department database with the diagnosis of GIST. We excluded duplicate and recurrent cases. We examined patients' files for the presence of RCC, adrenal tumors, or other genitourinary cancer. A systematic review of the association was conducted. From 2003 to 2020, 170 patients had a histopathologic diagnosis of primary GIST, 100 men and 70 women, median age of 57 (range 9-91) years at the time of diagnosis. The site of primary GIST was gastric 103, small bowel 43, mesenteric 5, omentum/peritoneum 7, abdomen 4, isolated adrenal 1, and other 7. Six patients had associated primary genitourinary cancer. Three patients had RCC (two clear cell RCC and one radiologic diagnosis only), and three had adrenal tumors (one adrenal carcinoma, one an isolated adrenal GIST, and one pheochromocytoma). In addition, two patients had a tumor invading the urinary bladder. Although the cohort included 63 men aged 60 or above (median 71 ± 8.7 years, range 60-94), none demonstrated clinical prostatic carcinoma. Data was compared to 69 systematic review articles. We report the rare association between GIST tumors and primary genitourinary cancer, mainly RCC and adrenal tumors. Also, we identified a secondary invasion of the urinary bladder. Unlike the reported series, none of the older male patients had clinical prostate cancer.