Different patterns of esophageal motility disorders among patients with dysphagia and normal endoscopy: A 2-center experience

Esophageal motility disorders (EMDs) are the main etiology of nonobstructive dysphagia (NOD), but they are underestimated in Egypt. High-resolution manometry (HRM) with Chicago Classification version 3.0 (CC v3.0) is the current gold standard diagnostic modality to assess EMD in patients with NOD. In this HRM-based study, we aimed to classify EMD among Egyptian patients and explore the relationship between the severity of symptoms and the various groups of EMD. From January 2020 to January 2021, patients with dysphagia were subjected to diagnostic workup, which included symptom questionnaire for Eckardt score, esophagogastroduodenoscopy, barium esophagogram, and HRM. All patients were categorized based on the HRM results using CC version 3.0 after exclusion of those with obstructive esophageal lesions. Of 252 patients with dysphagia, 55 patients with NOD were analyzed according to CC version 3.0. Achalasia was diagnosed in 31 patients (56.4%) (type I: 18 [58.06%]; type II: 9 [29.03%], and type III: 4 [12.9%]), 3 patients (5.5%) with esophagogastric junction outflow obstruction, 2 patients (3.6%) with absent contractility, 4 patients (7.3%) with distal esophageal spasm, 7 patients (12.7%) with ineffective esophageal motility, and 8 patients (14.5%) with normal manometry. Patients with achalasia experienced significantly high regurgitation (96.8% vs 70.8%; P = .016) compared with those without achalasia. Achalasia was the most common EMD in Egyptian patients with NOD. Eckardt score was higher in patients with outflow obstruction and major motor disorder, but it could not differentiate different categories of CC of EMD. HRM is effective in characterization of EMD.     

Use of a Rigid-Tipped Microguidewire for the Endovascular Treatment of Cavernous Sinus Dural Arteriovenous Fistulas with an Occluded Inferior Petrosal Sinus

ObjectiveTransvenous embolization (TVE) via an occluded inferior petrosal sinus (IPS) in a cavernous sinus dural arteriovenous fistula (CSDAVF) is challenging, often requiring navigation of a microcatheter through resistive obstacles between the occluded IPS and shunted pouch (SP), although the reopening technique was successfully performed. We report five cases of successful access to the cavernous sinus (CS) or SP using the rigid-tipped microguidewire such as chronic total occlusion (CTO) wire aiming to share our initial experience with this wire. MethodsIn this retrospective study, four patients with CSDAVF underwent five procedures using the CTO wire puncture during transfemoral transvenous coil embolization. Puncture success, shunt occlusion, and complications including any hemorrhage and cranial nerve palsy were evaluated. ResultsDespite successful access through the occluded IPS, further entry into the target area using neurointerventional devices was impossible due to a short-segment stricture before the CS (three cases) and a membranous barrier within the CS (two cases). However, puncturing these structures using the rigid-tipped microguidewire was successful in all cases. We could advance the microcatheter over the rigid-tipped microguidewire for the navigation to the SP and achieved complete occlusion of the SP without complications. ConclusionThe use of the rigid-tipped microguidewire in the TVE via the occluded IPS of the CSDAVF would be feasible and safe.     

Small extracellular vesicle-associated miR-6068 promotes aggressive phenotypes of prostate cancer through miR-6068/HIC2/SIRT1 axis

Early diagnosis and treatment of patients with aggressive prostate cancer (PCa) remains a clinically unmet need. We aimed to determine the levels of small extracellular vesicle (sEV)-associated microRNAs (miRs); miR-4737, miR-6068, and miR-6076 in a large panel of PCa cells and delineate the biological significance of miR-6068 in promoting PCa cells. sEVs were isolated from the conditioned medium of PCa cells, followed by RNA extraction and quantitative Real-Time PCR analysis. Functional assays were performed, and the protein expression of hypermethylated in cancer 2 (HIC2), as a potential miR-6068 target gene, was evaluated in PCa tissues by immunohistochemistry. sEV-associated miR-6068, miR-4737, and miR-6076 levels displayed large and significant differences compared to normal cells. miR-6068 was explicitly upregulated in sEV of PC-3 and CWR-R1ca cells (P<0.010). Suppression of miR-6068 in CWR-R1ca cells decreased cell proliferation, colony formation, and cell migration. In contrast, upregulation of miR-6068 in RC77T/E cells decreased HIC2 levels and increased cell aggressive phenotypes. The overexpression of HIC2 in PCa tissues was primarily observed in the cytoplasm compared to benign prostatic hyperplasia (BPH) and normal tissues (P<0.0001). This study confirms the differential packaging of miR-4737, miR-6068, and miR-6076 in sEVs of PCa cells. MiR-6068 promotes PCa cells to acquire aggressive phenotypes by inhibiting the HIC2/Sirtuin 1 (SIRT1) axis.     

Plasmodium falciparum pfhrp2 and pfhrp3 Gene Deletions and Relatedness to Other Global Isolates,Djibouti, 2019–2020

Deletions of pfhrp2 and paralogue pfhrp3 (pfhrp2/3) genes threaten Plasmodium falciparum diagnosis by rapid diagnostic test. We examined 1,002 samples from suspected malaria patients in Djibouti City, Djibouti, to investigate pfhrp2/3 deletions. We performed assays for Plasmodium antigen carriage, pfhrp2/3 genotyping, and sequencing for 7 neutral microsatellites to assess relatedness. By PCR assay, 311 (31.0%) samples tested positive for P. falciparum infection, and 296 (95.2%) were successfully genotyped; 37 (12.5%) samples were pfhrp2+/pfhrp3+, 51 (17.2%) were pfhrp2+/pfhrp3–, 5 (1.7%) were pfhrp2–/pfhrp3+, and 203 (68.6%) were pfhrp2–/pfhrp3–. Histidine-rich protein 2/3 antigen concentrations were reduced with corresponding gene deletions. Djibouti P. falciparum is closely related to Ethiopia and Eritrea parasites (pairwise G_ST 0.68 [Ethiopia] and 0.77 [Eritrea]). P. falciparum with deletions in pfhrp2/3 genes were highly prevalent in Djibouti City in 2019–2020; they appear to have arisen de novo within the Horn of Africa and have not been imported.     

Platinum-induced ototoxicity in pediatric cancer survivors: GSTP1 c.313A>G variant association

Hearing damage is one of the main toxic effects of platinum compounds, it derives from the irreversible degeneration of hair cells of the ear. Genetic association studies have suggested an association between GSTP1 c.313A>G variant and platinum-induced ototoxicity in childhood cancer survivors. We aimed to detect the frequency of ototoxicity and associated risk factors in survivors of childhood cancer receiving platinum-based chemotherapy and to detect the relation between GSTP1 c.313A>G (rs1695) polymorphisms and ototoxicity. We conducted a cross-sectional study on 64 cancer survivors who received platinum agents (cisplatin and/or carboplatin) at least 2 years after the end of chemotherapy. The patients underwent comprehensive audiological evaluations and genotyping to detect the presence of the GSTP1 c.313A>G polymorphisms. Hearing loss (HL) was identified in 16/64 patients (25%), including 62.5% treated with cisplatin and 37.5% treated with carboplatin. The greater incidence of ototoxicity was found in children treated for osteosarcoma (28.1%) followed by patients with germ cell tumors (25%) and neuroblastoma (21.9%). The AA, AG, and GG types of GSTP1 c.313A>G variant were detected in 84.4%, 9.4%, and 6.3%, respectively, of patients with HL with a significant association between mutant genotype of GSTP1 rs1695 and platinum-induced ototoxicity (P = .035). HL was not significantly associated with the total cumulative dose of cisplatin and carboplatin. GSTP1 c.313A>G variant may increase the risk of HL in pediatric oncology patients treated with cisplatin or carboplatin chemotherapy.     

The incidence of urethral stricture and bladder neck contracture with transurethral resection vs. holmium laser enucleation of prostate: A matched,dual-center study

IntroductionUrethral strictures (US) and bladder neck contracture (BNC) are common, long-term complications of transurethral prostate surgery. We aimed to compare transurethral resection of the prostate (TURP) and holmium laser enucleation of the prostate (HoLEP) regarding incidence of US or BNC and identify possible risk factors.MethodsA retrospective review of patients who underwent TURP and HoLEP with followup data of at least one year in two separate institutions was performed. The incidence of postoperative US or BNC in both groups was compared. Bivariate and multivariate analysis of risk factors in both cohorts with US or BNC were performed.ResultsThe study included 208 patients: 101 and 107 patients in the TURP and HoLEP arms, respectively. The two groups were matched for age and prostate size. Eight (7.92%) and five (4.72%) patients in the TURP and HoLEP arms, respectively, developed US (p=0.3423), while two (1.87%) patients in the HoLEP arm had BNC (p=0.2634). Of the eight patients with the US in the TURP arm, six (9.8%) had bipolar TURP, while two (5%) had monopolar TURP. Multivariate analysis showed that larger prostate volume (hazard ratio [HR] 1.22, 95% confidence interval [CI] 1.05, 1.41, p=0.0066) and longer operative time (HR 1.84, 95% CI 1.76, 1.93, p=0.0015) were associated with risk of US/BNC.ConclusionsThere is no significant difference between TURP and HoLEP regarding incidence of US or BNC, although there is a tendency towards a higher rate of US associated with bipolar TURP. Increased prostate volume and operative time are possible risk factors.

KEY MESSAGES

• We compared TURP and HoLEP regarding their incidence of US or BNC with matching patients for age and prostate volume and identified possible risk factors.
• The US incidence was comparable, although the incidence within the TURP arm was higher with bipolar than monopolar TURP.
• The BNC incidence was 1.87% in the HoLEP arm, while none of the patients in the TURP arm developed BNC (statistically insignificant).
• Multivariate analysis showed that larger prostate volume and longer operative time were associated with higher risk of US/BNC.