Cloacal Dysgenesis Sequence in a Preterm Neonate.

BACKGROUND Cloaca malformations result from a disproportion of apoptosis, cell growth, and maturation. The range of cloacal malformations is extensive and diverse, with a lack of a straightforward classification system. Cloacal dysgenesis sequence (CDS), also known as urorectal septum malformation sequence, is a rare cloaca variant described as the absence of a perineal orifice. Prenatal magnetic resonance imaging and antenatal ultrasounds may reveal a cloacal malformation; however, many patients are not diagnosed with cloacal malformation until birth. CASE REPORT We present a case of a female neonate delivered by a 23-year-old G2P1T1A0L0 mother who had received comprehensive prenatal care. During pregnancy, bilateral multicystic dysplastic kidneys were identified prenatally, leading to the in utero placement of a vesicoamniotic shunt. The physical exam revealed a distended abdomen with reduced abdominal musculature and laxity, ascites, a vesicoamniotic shunt in place, absent urethra, ambiguous genitalia with no vaginal opening, no perineal opening, and clubfoot. Abdominal radiograph showed findings consistent with significant abdominal ascites. An exploratory laparotomy was performed that included diverting colostomy, mucous fistula creation, tube vaginostomy, removal of the vesicoamniotic shunt, and suprapubic tube placement. The patient recovered well from this operation with no complications. CONCLUSIONS CDS is an uncommon condition in pediatric patients, and although sonographic findings can reveal urinary tract abnormalities, prenatal imaging might not always identify CDS. Our case underscores the uniqueness of the case and the significance of early detection and immediate medical and surgical intervention.

T2-based magnetic resonance genitography in children with complex anorectal malformations: experience at a tertiary pediatric hospital in Latin America.

In children with anorectal malformations (ARMs), it is essential to have a diagnostic imaging method that helps with the evaluation of the internal anatomy. In patients with a persistent cloaca, an ARM variant, in which the measurement of the urethral channel and common channel determines surgical management, there are multiple options for imaging. Magnetic resonance imaging (MRI) is an excellent method for this purpose, from which accurate measurements of channel length can be obtained. Additionally, the use of volumetric/isotropic sequences allows multiplanar reformatting. We present our experience with pelvic MRI and intracavitary non-paramagnetic contrast (MR genitography). This method uses volumetric T2-weighted images and the instillation of saline solution as a contrast agent to distinguish the common channel, length of the urethra, anatomy of the vagina, and presence and location of the rectal fistula. We believe this technique to be particularly useful for those working in settings with limited MRI resources.

Anatomical Gynecological Anomalies in Girls Born with Anorectal Malformations: A Retrospective Cohort Study of 128 Patients.

STUDY OBJECTIVE: In girls born with an anorectal malformation (ARM), anatomical gynecological anomalies (GA) may be present and might need treatment. Therefore, the aim of this study was to provide an overview of GA in girls born with ARM in our cohort. Additionally, diagnostic timing and methods for GA were assessed. METHODS: A retrospective mono-center study was performed from January 2000 to December 2022. All patients assigned female at birth were eligible for inclusion. GA were classified according to ESHRE/ESGE classification. Outcomes were the number of girls with GA with subsequent screening methods, factors associated with GA, and GA requiring treatment. Uni- and multivariable logistic regression analyses were performed to identify the association between baseline characteristics and the presence of GA. RESULTS: In total, 128 girls were included, of whom 30 (24.1%) had additional GA, with vaginal anomalies being present most often (n = 17). Fifty-six patients (43.8%) underwent full screening, and this number improved over time (37.7% before 2018 vs 72.7% after 2018; P = .003). Thirteen of 30 patients (43.3%) required surgical treatment for their GA, without the occurrence of postoperative complications. CONCLUSION: Additional GA were present in almost a quarter of the girls born with an ARM, with vaginal anomalies most often identified. Despite GA being most often found in patients with cloacal malformations, these anomalies were also identified in patients with other ARM types. Surgical treatment was required in almost half of the girls with GA. Therefore, this study emphasizes the importance of screening for GA in patients with an ARM, regardless of the ARM type.

Enterococcus cecorum lesion strains are less sensitive to the hostile environment of albumen and more resistant to lysozyme compared to cloaca strains.

RESEARCH HIGHLIGHTS: Egg albumen inhibits Enterococcus cecorum cloaca strains more than lesion strains.Enterococcus cecorum lesion strains are resistant to high concentrations of lysozyme.Lysozyme resistance could enhance survival in albumen and body fluids.

Fetal ascites in cloacal malformations-a red flag.

INTRODUCTION: Cloacal malformation is a rare anomaly that remains a diagnostic challenge prenatally, despite the current advances in ultrasonography and MRI. This condition can in some, present with isolated ascites or with other findings, such as a pelvic cyst or upper urinary tract dilatation. In a minority, the ascites may be progressive, questioning the role of antenatal intervention. METHODS: We report on ten patients that have been identified from our Cloaca database between 2010 and 2022. RESULTS: The presence of ascites was associated with extensive bowel adhesions and matting, leading to a challenging initial laparotomy and peri-operative course. CONCLUSIONS: Antenatal finding of ascites in newborns with cloacal malformations should raise a red flag. The surgeon and anaesthetist should be prepared for the operative difficulties secondary to bowel adhesions and the higher risk of haemodynamic instability at the initial surgery. An experienced team at initial laparotomy in such patients is vital. LEVEL OF EVIDENCE: II.

Larvicidal and anti-termite activities of microbial biosurfactant produced by Enterobacter cloacae SJ2 isolated from marine sponge Clathria sp.

The widespread use of synthetic pesticides has resulted in a number of issues, including a rise in insecticide-resistant organisms, environmental degradation, and a hazard to human health. As a result, new microbial derived insecticides that are safe for human health and the environment are urgently needed. In this study, rhamnolipid biosurfactants produced from Enterobacter cloacae SJ2 was used to evaluate the toxicity towards mosquito larvae (Culex quinquefasciatus) and termites (Odontotermes obesus). Results showed dose dependent mortality rate was observed between the treatments. The 48 h LC50 (median lethal concentration) values of the biosurfactant were determined for termite and mosquito larvae following the non-linear regression curve fit method. Results showed larvicidal activity and anti-termite activity of biosurfactants with 48 h LC50 value (95% confidence interval) of 26.49 mg/L (25.40 to 27.57) and 33.43 mg/L (31.09 to 35.68), respectively. According to a histopathological investigation, the biosurfactant treatment caused substantial tissue damage in cellular organelles of larvae and termites. The findings of this study suggest that the microbial biosurfactant produced by E. cloacae SJ2 is an excellent and potentially effective agent for controlling Cx. quinquefasciatus and O. obesus.

Sexual and Reproductive Health Concerns in Adults With Cloacal Anomalies: A Qualitative Study.

STUDY OBJECTIVE: Long-term gynecologic data are lacking to inform the care of patients with cloacal malformations. We seek to examine perceived sexual and reproductive health challenges of patients born with cloacal anomalies and characterize the experiences of patients as adults. DESIGN AND SETTING: Virtual semi-structured focus groups and single-participant interviews were conducted using an online video platform. Retrospective chart review was performed to abstract available demographics and surgical history. PARTICIPANTS: Adult patients were contacted from a database of 143 patients born with cloaca who had been seen at or referred to a tertiary care pediatric colorectal center. Participants were recruited until data collection reached thematic saturation. Twenty patients aged 18-53 years participated in 5 focus groups and 3 single-participant interviews. The hospital IRB determined the research activities to be exempt from IRB review and oversight. INTERVENTIONS AND MAIN OUTCOME MEASURES: Interviews and focus groups were transcribed and analyzed using the constant comparative method to identify themes regarding sexual and reproductive health and compared with medical and surgical history abstracted from chart review. RESULTS: Participants reported many perceived barriers to intercourse and intimacy including bowel and bladder continence management. All participants reported discussion of pregnancy and fertility with healthcare providers as important. Other common themes included concerns about independence and transitioning from pediatric to adult providers. CONCLUSION: Anorectal malformations are associated with sexual and reproductive health concerns. Patients seek guidance on family building, intimacy, and transition to adult care. Future quantitative study of these topics is needed to develop best practices for counseling and clinical management of these patients. LEVEL OF EVIDENCE: Level VI. TYPE OF STUDY: Prognosis Study.

Enterobacter cloacae infection characteristics and outcomes in battlefield trauma patients.

Enterobacter cloacae is a Gram-negative rod with multidrug-resistant potential due to chromosomally-induced AmpC ß-lactamase. We evaluated characteristics, antibiotic utilization, and outcomes associated with battlefield-related E. cloacae infections (2009-2014). Single initial and serial E. cloacae isolates (≥24 hours from initial isolate from any site) associated with a clinical infection were examined. Susceptibility profiles of initial isolates in the serial isolation group were contrasted against last isolate recovered. Characteristics of 112 patients with E. cloacae infections (63 [56%] with single initial isolation; 49 [44%] with serial isolation) were compared to 509 patients with bacterial infections not attributed to E. cloacae. E. cloacae patients sustained more blast trauma (78%) compared to non-E. cloacae infections patients (75%; p<0.001); however, injury severity scores were comparable (median of 34.5 and 33, respectively; p = 0.334). Patients with E. cloacae infections had greater shock indices (median 1.07 vs 0.92; p = 0.005) and required more initial blood products (15 vs. 14 units; p = 0.032) compared to patients with non-E. cloacae infections. Although E. cloacae patients had less intensive care unit admissions (80% vs. 90% with non-E. cloacae infection patients; p = 0.007), they did have more operating room visits (5 vs. 4; p = 0.001), longer duration of antibiotic therapy (43.5 vs. 34 days; p<0.001), and lengthier hospitalizations (57 vs. 44 days; p<0.001). Patients with serial E. cloacae had isolation of infecting isolates sooner than patients with single initial E. cloacae (median of 5 vs. 8 days post-injury; p = 0.046); however, outcomes were not significantly different between the groups. Statistically significant resistance to individual antibiotics did not develop between initial and last isolates in the serial isolation group. Despite current combat care and surgical prophylaxis guidelines recommending upfront provision of AmpC-inducing antibiotics, clinical outcomes did not differ nor did significant antibiotic resistance develop in patients who experienced serial isolation of E. cloacae versus single initial isolation.

Long-term urological outcome of cloaca patients with multidisciplinary management.

PURPOSE: Urological management of Cloacal Malformation (CM) focuses on preserving renal function and continence. Study aim was to analyze urinary and intestinal outcomes in CM patients, considering the length of common channel (CC) and presence of occult spinal dysraphism (OSD). METHODS: Retrospective review of CM treated at our institution by a multidisciplinary team from 1999 to 2020. Patients with follow-up < 2.5 years were excluded. Length of CC, renal function, urinary and bowel outcomes, presence of associated anomalies (especially OSD) were evaluated. RESULTS: Twenty patients were included, median age at follow-up: 8 years (4-15). A long CC > 3 cm was described in 11 (55%). Chronic kidney disease was found in 3 patients. Urinary continence was achieved in 8/20 patients, dryness (with intermittent catheterization) in 9/20. Fecal continence was obtained in 3/20, cleanliness in 14 (under bowel regimen). OSD was present in 10 patients (higher prevalence in long-CC, 73%). Among OSD, 1 patient reached fecal continence, 7 were clean; 2 achieved urinary continence, while 6 were dry. CONCLUSIONS: Length of CC and OSD may affect urinary and fecal continence. An early counseling can improve outcome at long-term follow-up. Multidisciplinary management with patient centralization in high grade institutions is recommended to achieve better results.

Posterior sagittal anorecto-urethro-vagino-plasty in the late period was associated with the long-term bowel function in patients with persistent cloaca: results of a nationwide survey in Japan.

PURPOSE: After conducting a nationwide survey of persistent cloaca (PC), we assessed whether or not the timing of definitive anorectoplasty affects the long-term bowel function of patients with PC. METHODS: Patient information was obtained via questionnaire, and a total of 169 PC patients who underwent posterior sagittal anorectourethrovaginoplasty (PSARUVP) were enrolled in this study. Patients were classified into 2 groups based on their operative period, which was analyzed by the area under the receiver operating characteristic curve: the early group (EG) underwent anorectoplasty at ≤ 18 months old (n = 106), and the late group (LG) underwent anorectoplasty at > 18 months old (n = 63). The bowel function was evaluated using the evacuation score of the Japan Society of Anorectal Malformation Study Group. We also examined the postoperative results of vaginoplasty. RESULTS: The total evacuation score was significantly higher in the EG than in the LG (5.2 ± 1.7 vs. 4.2 ± 1.8, p = 0.003). The frequency of bowel movement and the constipation scores were significantly higher in the EG than in the LG (1.4 ± 0.6 vs. 1.2 ± 0.7, p < 0.05, 2.4 ± 1.0 vs. 2.1 ± 1.0, p < 0.05, respectively). Postoperative vaginal stenosis was observed in 18 cases (10.7%), of which 16 could be reconstructed transperineally. CONCLUSION: PSARUVP should be performed in early infancy and facilitate vaginal reconstruction.

Perinatal diagnosis of congenital urogenital sinus abnormality.

Anomalies of the urogenital sinus, which is a transient feature of the early human embryological development, are rare birth defects. Urogenital sinus abnormalities commonly present as pelvic masses, hydrometrocolpos, or ambiguous genitalia and most commonly occur within the context of congenital adrenal hyperplasia. Anomalies of the urogenital sinus requires surgical repair. We experienced a case of a female newborn with congenital urogenital sinus abnormality in which the early diagnosis helped us to prevent complications by decompressing the vagina soon after birth. Antibiotic prophylaxis was sufficient to avoid infections and to decompress the genitourinary system, thus allowing a deferred elective surgery to correct the sinus.

Long-term 10-year comparison of girls with congenital adrenal hyperplasia who underwent early and late feminizing genitoplasty.

OBJECTIVES: The appropriate time to perform feminizing genitoplasty in patients with congenital adrenal hyperplasia (CAH) with the 46, XX genotype is still debatable. The aim of our study was to evaluate the relationship between age at surgery and long-term surgical outcomes of patients who underwent feminizing genitoplasty. METHODS: We retrospectively analyzed 14 patients with CAH and 46, XX genotypes with feminizing genitoplasty (clitoroplasty + vaginoplasty) between 2005 and 2022. The patients were divided into two groups. Group 1 consisted of seven girls (n = 7/14) who have been operated before the age of 2 years. Group 2 consisted of seven girls (n = 7/14) who have been operated after the age of 2 years. The two groups are compared regarding anatomical assessments, overall cosmetic results, need for additional intervention using Creighton's criteria. Additionally, the cosmetical satisfaction of the patients/parents is questioned. RESULTS: The mean age of the girls was 32.42 months (10-96 months) during operation time. The mean age of Group 1 patients (n = 7/14) who have been operated before the age of 2 years was 11.71 months (10-19 months). The mean age of Group 2 patients (n = 7/14) who have been operated after the age of 2 years was 53.14 months (36-96 months). The mean follow-up time was 10.57 years (3-18 years). There was no statistically significant difference between those operated on before and after two years in terms of anatomical assessments, overall cosmetic results and patient/parent satisfaction except the need for additional intervention (p = 0.049). In Group1 (operation age < 2 years old), five out of seven (71.42%) patients needed additional major surgery (four urogenital sinus re-mobilization, one redo-clitoroplasty). Those who received additional major surgery were the ones who were not satisfied. In Group 2 (operation age > 2 years old), two patients out of seven patients (28.57%) received major surgery (two redo-urethroplasties) and those patients were not satisfied. When patient/parent satisfaction was compared with additional surgical intervention, as expected, patients'/parents' satisfaction increased as major surgical intervention decreased. This was statistically significant (p = 0.007). The main source of dissatisfaction was repeated surgery among the parents. CONCLUSIONS: The possibility of this additional surgical intervention increases, and patient/parent satisfaction decreases in patients below the age of 2 years. The corrective surgeries can be differed until the gender identity of the patient matures and the patient autonomy in deciding whether this surgery should occur.

Social signal manipulation and environmental challenges have independent effects on physiology, internal microbiome, and reproductive performance in tree swallows (Tachycineta bicolor).

The social environment that individuals experience appears to be a particularly salient mediator of stress resilience, as the nature and valence of social interactions are often related to subsequent health, physiology, microbiota, and overall stress resilience. Relatively few studies have simultaneously manipulated the social environment and ecological challenges under natural conditions. Here, we report the results of experiments in wild tree swallows (Tachycineta bicolor) in which we manipulated both ecological challenges (predator encounters and flight efficiency reduction) and social interactions (by experimental dulling of a social signal). In two experiments conducted in separate years, we reversed the order of these treatments so that females experienced either an altered social signal followed by a challenge or vice-versa. Before, during, and after treatments were applied, we tracked breeding success, morphology and physiology (mass, corticosterone, and glucose), nest box visits via an RFID sensor network, cloacal microbiome diversity, and fledging success. Overall, we found that predator exposure during the nestling period reduced the likelihood of fledging and that signal manipulation sometimes altered nest box visitation patterns, but little evidence that the two categories of treatment interacted with each other. We discuss the implications of our results for understanding what types of challenges and what conditions are most likely to result in interactions between the social environment and ecological challenges.

Mannheimia cairinae sp. nov., a novel species of Mannheimia obtained from Muscovy ducks (Cairina moschata) and reclassification of Mannheimia ovis as heterotypic synonym of Mannheimia pernigra.

During a screening study for Pasteurella multocida in two unrelated flocks of Muscovy ducks pharyngeal and cloacal swabs were collected. A total of 59 Pasteurellaceae-like isolates sharing the same colony morphology were subcultured and subsequently characterized. Colonies on bovine blood agar were nonhaemolytic, regular, circular, slightly raised, shiny, intransparent with an entire margin, greyish and had an unguent-like consistency. Isolate AT1T was characterized by 16S rRNA gene sequencing and showed the highest similarity of 96.1 % to the type strain of Mannheimia caviae and 96.0 % to the type strain of Mannheimia bovis, respectively. In addition, rpoB and recN gene sequences also showed the highest similarity to the genus Mannheimia. The phylogenetic comparison of concatenated conserved protein sequences also showed a unique position of AT1T compared to other species of Mannheimia. Full phenotypic characterization of the isolates showed that between two (Mannheimia ruminalis) and 10 (Mannheimia glucosida) phenotypic characteristics separate the taxon isolated from Muscovy ducks from the accepted species of Mannheimia. Whole genomic sequences of two strains analysed by the type strain genome server showed the highest similarity of 24.9 % to the genome of the type strain of Pasteurella multocida and 23.0 % to the genome of the type strain of Mannheimia haemolytica. The species Mannheimia cairinae sp. nov. is proposed based on the phenotypic and genotypic similarity to Mannheimia as well as differences to the other validly published species of the genus. The leukotoxin protein was not predicted in the genome of AT1T. The G+C content of the type strain of M. cairinae sp. nov., AT1T (=CCUG 76754T=DSM 115341T) is 37.99 mol%, calculated from the whole genome. The investigation further proposes that Mannheimia ovis is reclassified as a later heterotypic synonym of Mannheimia pernigra, since M. ovis and M. pernigra are closely genetically related, and M. pernigra was validly published before M. ovis.

Inversin (NPHP2) and Vangl2 are required for normal zebrafish cloaca formation.

Nephronophthisis (NPH), an autosomal recessive ciliopathy, results from mutations in more than 20 different genes (NPHPs). These gene products form protein complexes that regulate trafficking within the cilium, a microtubular structure that plays a crucial role in developmental processes. Several NPHPs, including NPHP2/Inversin, have been linked to extraciliary functions. In addition to defining a specific segment of primary cilia (Inversin compartment), NPHP2 participates in planar cell polarity (PCP) signaling along with Dishevelled and Vangl family members. We used the mutant zebrafish line invssa36157, containing a stop codon at amino acid 314, to characterize tissue-specific functions of zebrafish Nphp2. The invssa36157 line exhibits mild ciliopathy phenotypes and increased glomerular and cloaca cyst formation. These mutants showed enhanced susceptibility to the simultaneous depletion of the nphp1/nphp2/nphp8 module, known to be involved in the cytoskeletal organization of epithelial cells. Notably, simultaneous depletion of zebrafish nphp1 and vangl2 led to a pronounced increase in cloaca malformations in the invssa36157 mutant embryos. Time-lapse imaging showed that the pronephric cells correctly migrated towards the ectodermal cells in these embryos, but failed to form the cloaca opening. Despite these abnormal developments, cellular fate does not seem to be affected in nphp1 and vangl2 MO-depleted invssa36157 mutants, as shown by in situ hybridizations for markers of pronephros and ectodermal cell development. However, significantly reduced apoptotic activity was observed in this double knockdown model, signifying the role of apoptosis in cloacal morphogenesis. Our findings underscore the critical interplay of nphp1, nphp2/Inversin, and vangl2 in orchestrating normal cloaca formation in zebrafish, shedding light on the complex molecular mechanisms underlying ciliopathy-associated phenotypes.

Partial urogenital mobilization in cloacal malformation: is it a viable option?

INTRODUCTION: Total Urogenital Mobilization (TUM) has been the standard surgical approach for the urogenital complex in Cloacal Malformations (CM) since its inception in 1997. Partial Urogenital Mobilization (PUM) in CM remains an under-utilized or under-reported option. The main anatomical difference between TUM and PUM is the division of the pubo-urethral ligaments. OBJECTIVE: We explored the feasibility of PUM in a select subset of our patients with CM and report early outcomes. STUDY DESIGN: We retrospectively reviewed prospectively collected data of all our CM patients who had primary reconstruction at our centre from 2012 to 2020. We included in our review the patients who underwent PUM. Mullerian abnormalities, spinal cord involvement, common channel length (CC), urethral length (UL), surgical reconstruction, and outcomes including urinary continence, recurrent UTI, ultrasound and preoperative DMSA/MAG3, cystovaginoscopy post-reconstruction, and post-void residuals were noted. RESULTS: Fifty-three patients had primary reconstruction, and of these, eleven had a common channel less than 3 cm. Of the eleven, only one underwent TUM. In the PUM group, two underwent filum untethering (20%). Mullerian duplication was noted in 5 patients (50%). The median CC length = 1.6 cm (range = 1.5cm-2.7 cm), and median UL = 1.5 cm (range = 1.5cm-2.5 cm). Follow-up ranged from 9 to 134months (median = 63months). Post-reconstruction all had a separate urethral and vaginal opening on examination and cysto-vaginoscopy. The continence outcomes are summarized in Fig.1. DISCUSSION: Although TUM is the most common solution for the urogenital complex in CM, a subset would be suitable for PUM, and this option is under-utilized or under-reported in literature. We presume that many who had TUM probably only needed a PUM, and therefore could report better outcomes from a bladder function aspect. It is important to differentiate the two, and outcomes should be appropriately categorized. Our default approach is a PUM in all CM with less than 3 cm common channel. Only the lateral and posterior aspects of the urogenital complex are mobilized and if the urethra did not reach a satisfactory level for easy intermittent catheterization, then we proceed to a TUM dividing the pubo-urethral ligaments. PUM avoids the potential complications related to dividing the pubo-urethral ligament in TUM. It may also avoid the need for CIC which is encountered in patients who undergo TUM. CONCLUSION: PUM is a viable alternative in cloacal malformations with good outcomes in those with a common channel under 3 cm. This of course requires appropriate patient selection and accurate categorization of interventions to understand the true outcomes.