Review of the Messorsemirufus complex (Hymenoptera, Formicidae) in Greece.

Messor is a diverse genus of Myrmicinae with 168 extant species and subspecies. In the Mediterranean, some of its taxa historically were classified as members of the Messorinstabilis group (sensu Santschi), of which 19 are known from the eastern Mediterranean. Here, the Messorsemirufus complex of the Balkan Peninsula that assembles a distinct subsection of members of the instabilis group is defined and treated. In total, five species are recorded, including three that are new. Messoratanassovii Atanassov, 1982 is redescribed and confirmed for Bulgaria (Thracian Plain, Struma, and Mesta Valley, Pirin Mt., and Eastern Rhodopi) and Greece (Epirus, Ionian Islands, Central and Eastern Macedonia, and Thraki). Three species are described as new to science: Messordanaes Salata, Georgiadis & Borowiec, sp. nov. (Cyclades: Serifos), Messorkardamenae Salata & Borowiec, sp. nov. (Dodecanese: Kos, Nisyros, Rhodes, and Tilos), and Messorveneris Salata, Georgiadis & Borowiec, sp. nov. (Cyclades: Milos). The fifth member of the complex, Messorcreticus Borowiec & Salata, 2019, maintains its status of Cretan endemic.

The ant genus Cataglyphis Förster (Hymenoptera: Formicidae) in Cyprus.

The comprehensive survey of the ant fauna conducted in Cyprus revealed that the island is inhabited by two species of the genus Cataglyphis Förster, 1850. Both species are endemic and are described as new to science. Cataglyphis chionistrae n. sp., a member of the C. cursor species complex, occurs only in the high montane pine forest of Mt. Chionistra (= Mt. Olympos). While C. aphrodite n. sp., a member of the C. nodus species complex, is common at low and mid altitudes in open habitats or luminous pine forests. This work also provides the key to Cataglyphis from Cyprus and the very first synopsis lists of all the members of the cursor and nodus species complexes known from the Eastern Mediterranean Region.

Base-Edited CAR7 T Cells for Relapsed T-Cell Acute Lymphoblastic Leukemia.

BACKGROUND: Cytidine deamination that is guided by clustered regularly interspaced short palindromic repeats (CRISPR) can mediate a highly precise conversion of one nucleotide into another - specifically, cytosine to thymine - without generating breaks in DNA. Thus, genes can be base-edited and rendered inactive without inducing translocations and other chromosomal aberrations. The use of this technique in patients with relapsed childhood T-cell leukemia is being investigated. METHODS: We used base editing to generate universal, off-the-shelf chimeric antigen receptor (CAR) T cells. Healthy volunteer donor T cells were transduced with the use of a lentivirus to express a CAR with specificity for CD7 (CAR7), a protein that is expressed in T-cell acute lymphoblastic leukemia (ALL). We then used base editing to inactivate three genes encoding CD52 and CD7 receptors and the ß chain of the αß T-cell receptor to evade lymphodepleting serotherapy, CAR7 T-cell fratricide, and graft-versus-host disease, respectively. We investigated the safety of these edited cells in three children with relapsed leukemia. RESULTS: The first patient, a 13-year-old girl who had relapsed T-cell ALL after allogeneic stem-cell transplantation, had molecular remission within 28 days after infusion of a single dose of base-edited CAR7 (BE-CAR7). She then received a reduced-intensity (nonmyeloablative) allogeneic stem-cell transplant from her original donor, with successful immunologic reconstitution and ongoing leukemic remission. BE-CAR7 cells from the same bank showed potent activity in two other patients, and although fatal fungal complications developed in one patient, the other patient underwent allogeneic stem-cell transplantation while in remission. Serious adverse events included cytokine release syndrome, multilineage cytopenia, and opportunistic infections. CONCLUSIONS: The interim results of this phase 1 study support further investigation of base-edited T cells for patients with relapsed leukemia and indicate the anticipated risks of immunotherapy-related complications. (Funded by the Medical Research Council and others; ISRCTN number, ISRCTN15323014.).

Cytosine Deaminase Base Editing to Restore COL7A1 in Dystrophic Epidermolysis Bullosa Human: Murine Skin Model.

Recessive dystrophic epidermolysis bullosa is a debilitating blistering skin disorder caused by loss-of-function mutations in COL7A1, which encodes type VII collagen, the main component of anchoring fibrils at the dermal-epidermal junction. Although conventional gene therapy approaches through viral vectors have been tested in preclinical and clinical trials, they are limited by transgene size constraints and only support unregulated gene expression. Genome editing could potentially overcome some of these limitations, and CRISPR/Cas9 has already been applied in research studies to restore COL7A1 expression. The delivery of suitable repair templates for the repair of DNA cleaved by Cas9 is still a major challenge, and alternative base editing strategies may offer corrective solutions for certain mutations. We show highly targeted and efficient cytidine deamination and molecular correction of a defined recessive dystrophic epidermolysis bullosa mutation (c.425A>G), leading to restoration of full-length type VII collagen protein expression in primary human fibroblasts and induced pluripotent stem cells. Type VII collagen basement membrane expression and skin architecture were restored with de novo anchoring fibrils identified by electron microscopy in base-edited human recessive dystrophic epidermolysis bullosa grafts recovered from immunodeficient mice. The results show the potential and promise of emerging base editing technologies in tackling inherited disorders with well-defined single nucleotide mutations.

Phase 1 clinical trial of CRISPR-engineered CAR19 universal T cells for treatment of children with refractory B cell leukemia.

Genome editing of allogeneic T cells can provide "off-the-shelf" alternatives to autologous chimeric antigen receptor (CAR) T cell therapies. Disruption of T cell receptor α chain (TRAC) to prevent graft-versus-host disease (GVHD) and removal of CD52 (cluster of differentiation 52) for a survival advantage in the presence of alemtuzumab have previously been investigated using transcription activator-like effector nuclease (TALEN)-mediated knockout. Here, we deployed next-generation CRISPR-Cas9 editing and linked CAR expression to multiplexed DNA editing of TRAC and CD52 through incorporation of self-duplicating CRISPR guide RNA expression cassettes within the 3' long terminal repeat of a CAR19 lentiviral vector. Three cell banks of TT52CAR19 T cells were generated and cryopreserved. A phase 1, open-label, non-randomized clinical trial was conducted and treated six children with relapsed/refractory CD19-positive B cell acute lymphoblastic leukemia (B-ALL) (NCT04557436). Lymphodepletion included fludarabine, cyclophosphamide, and alemtuzumab and was followed by a single infusion of 0.8 × 106 to 2.0 × 106 CAR19 T cells per kilogram with no immediate toxicities. Four of six patients infused with TT52CAR19 T cells exhibited cell expansion, achieved flow cytometric remission, and then proceeded to receive allogeneic stem cell transplantation. Two patients required biological intervention for grade II cytokine release syndrome, one patient developed transient grade IV neurotoxicity, and one patient developed skin GVHD, which resolved after transplant conditioning. Other complications were within expectations, and primary safety objectives were met. This study provides a demonstration of the feasibility, safety, and therapeutic potential of CRISPR-engineered immunotherapy.

The global distribution of known and undiscovered ant biodiversity.

Invertebrates constitute the majority of animal species and are critical for ecosystem functioning and services. Nonetheless, global invertebrate biodiversity patterns and their congruences with vertebrates remain largely unknown. We resolve the first high-resolution (~20-km) global diversity map for a major invertebrate clade, ants, using biodiversity informatics, range modeling, and machine learning to synthesize existing knowledge and predict the distribution of undiscovered diversity. We find that ants and different vertebrate groups have distinct features in their patterns of richness and rarity, underscoring the need to consider a diversity of taxa in conservation. However, despite their phylogenetic and physiological divergence, ant distributions are not highly anomalous relative to variation among vertebrate clades. Furthermore, our models predict that rarity centers largely overlap (78%), suggesting that general forces shape endemism patterns across taxa. This raises confidence that conservation of areas important for small-ranged vertebrates will benefit invertebrates while providing a "treasure map" to guide future discovery.

More than meets the eye: A case of synchronous ipsilateral clear cell renal cell carcinoma and urothelial carcinoma of the pelvicalyceal system and literature review.

BACKGROUND AND AIM: The synchronous occurrence of renal cell carcinoma and urothelial carcinoma of the renal pelvis in the same kidney is extremely rare, although previously reported. With this study we aim to present our case and provide a literature review on this entity. METHODS: An otherwise healthy 43-year-old military male with the chief complaint of left plank pain was seen in the office. Imaging revealed the presence of a 3.5 cm left renal mass. Left laparoscopic radical nephrectomy was performed for presumed renal malignancy. Pathology confirmed the presence of a clear cell RCC and revealed an area of low-grade UC arising from the ipsilateral renal pelvis, not visible in the preoperative imaging. Furthermore, a Pubmed database search in English language was conducted, up to June 2021, to identify the rate of simultaneous RCC and UC of the renal pelvis or ureter in RN specimen performed for presumed RCC or renal malignancy and subsequent management in these cases. RESULTS: A total of 53 articles reporting on 56 patients with synchronous ipsilateral RCC and UC of the renal pelvis were identified, together with our case. Eight cases (14%) were initially managed with RN, thereby requiring further management of the ureteral stump. Of these, six (75%) were managed with distal ureterectomy, one (12.5%) with active surveillance of the ureteral stump, while one case (12.5%) did not report subsequent management. To our knowledge, we present the youngest patient recorded in the literature, with this histology combination presenting synchronously in the same kidney. CONCLUSIONS: Although uncommon, the final pathology report may reveal neoplasms of dissimilar histology that may involve the renal pelvis. It is crucial for urologists and pathologists to be vigilant of such cases during a solid renal mass workup. Additional therapeutic adjustments may be necessitated, derailing the initial treatment plan.

Alientoma, a Dynamic Database for Alien Insects in Greece and Its Use by Citizen Scientists in Mapping Alien Species.

Invasive alien species have been increasingly acknowledged as a major threat to native biodiversity and ecosystem services, while their adverse impacts expand to human health, society and the economy on a global scale. Insects represent one of the most numerous alien organismic groups, accounting for about one fifth of their total number. In Greece, a large number of alien insects have been identified, currently reaching 469 species. In recent decades, the contribution of citizen science towards detecting and mapping the distribution of alien insects has been steeply increasing. Addressing the need for up-to-date information on alien species as well as encouraging public participation in scientific research, the Alientoma website-derived from "alien" and the Greek word "entoma", meaning insects, is presented. The website aims towards providing updated information on alien species of insects to the public as well as the scientific community, raising awareness about biological invasions and addressing their distribution and impacts inter alia. By maintaining a dynamic online database alongside a strong social media presence since its launch, Alientoma has attracted individuals mainly from Greece and Cyprus, interacting with the website through a total of 1512 sessions. Alientoma intends to establish a constantly increasing network of citizen scientists and to supplement early detection, monitoring and management efforts to mitigate the adverse impacts of alien insects in Greece.

Base-edited CAR T cells for combinational therapy against T cell malignancies.

Targeting T cell malignancies using chimeric antigen receptor (CAR) T cells is hindered by 'T v T' fratricide against shared antigens such as CD3 and CD7. Base editing offers the possibility of seamless disruption of gene expression of problematic antigens through creation of stop codons or elimination of splice sites. We describe the generation of fratricide-resistant T cells by orderly removal of TCR/CD3 and CD7 ahead of lentiviral-mediated expression of CARs specific for CD3 or CD7. Molecular interrogation of base-edited cells confirmed elimination of chromosomal translocations detected in conventional Cas9 treated cells. Interestingly, 3CAR/7CAR co-culture resulted in 'self-enrichment' yielding populations 99.6% TCR-/CD3-/CD7-. 3CAR or 7CAR cells were able to exert specific cytotoxicity against leukaemia lines with defined CD3 and/or CD7 expression as well as primary T-ALL cells. Co-cultured 3CAR/7CAR cells exhibited highest cytotoxicity against CD3 + CD7 + T-ALL targets in vitro and an in vivo human:murine chimeric model. While APOBEC editors can reportedly exhibit guide-independent deamination of both DNA and RNA, we found no problematic 'off-target' activity or promiscuous base conversion affecting CAR antigen-specific binding regions, which may otherwise redirect T cell specificity. Combinational infusion of fratricide-resistant anti-T CAR T cells may enable enhanced molecular remission ahead of allo-HSCT for T cell malignancies.

Retroperitoneal ganglioneuroma causing chronic lower back and leg pain in an 80-year-old man: A case report.

INTRODUCTION: and importance: Retroperitoneal ganglioneuromas that cause lower back and leg pain are extremely rare and are often misdiagnosed. Surgical resection has excellent prognosis in long-term survival. CASE PRESENTATION: We present an 80-year-old man with two-year worsening left lower back and leg pain. He was treated as presumed lumbar spine spondylosis with several courses of physical therapy together with medical treatment. An abdomen CT scan disclosed a tumour in the left retrorenal space. The tumour was resected and the histopathologic examination suggested a completely excised retroperitoneal ganglioneuroma. During one-year follow-up the patient is free of pain without any local recurrence. CLINICAL DISCUSSION: Retroperitoneal ganglioneuromas are rare benign tumors that originate from neural crest-derived cells of the paravertebral sympathetic plexus and sometimes from the adrenal medulla. They are usually asymptomatic and discovered on routine clinical examination or on autopsy. Occasionally they may show symptoms due to local pressure effect or rarely they are hormonally active and present with adrenergic symptoms. Complete resection of the tumor is important in order establish the final diagnosis and alleviate symptoms from pressure effects. CONCLUSION: This case highlights the need for great vigilance among physicians in order to consider any possible retroperitoneal pathology when indicated in the differential diagnosis of lower back and leg pain, before establishing other more common diagnosis, especially in the older population.

CRISPR-Mediated Base Conversion Allows Discriminatory Depletion of Endogenous T Cell Receptors for Enhanced Synthetic Immunity.

Emerging base editing technology exploits CRISPR RNA-guided DNA modification effects for highly specific C > T conversion, which has been used to efficiently disrupt gene expression. These tools can enhance synthetic T cell immunity by restricting specificity, addressing histocompatibility leukocyte antigen (HLA) barriers, and promoting persistence. We report lentiviral delivery of a hepatitis B-virus (HBV)-specific recombinant T cell receptor (rTCR) and a linked CRISPR single-guide RNA for simultaneous disruption of endogenous TCRs (eTCRs) when combined with transient cytosine deamination. Discriminatory depletion of eTCR and coupled expression of rTCR resulted in enrichment of HBV-specific populations from 55% (SEM, ±2.4%) to 95% (SEM, ±0.5%). Intensity of rTCR expression increased 1.8- to 2.9-fold compared to that in cells retaining their competing eTCR, and increased cytokine production and killing of HBV antigen-expressing hepatoma cells in a 3D microfluidic model were exhibited. Molecular signatures confirmed that seamless conversion of C > T (G > A) had created a premature stop codon in TCR beta constant 1/2 loci, with no notable activity at predicted off-target sites. Thus, targeted disruption of eTCR by cytosine deamination and discriminatory enrichment of antigen-specific T cells offers the prospect of enhanced, more specific T cell therapies against HBV-associated hepatocellular carcinoma (HCC) as well as other viral and tumor antigens.

CD70 expression determines the therapeutic efficacy of expanded human regulatory T cells.

Regulatory T cells (Tregs) are critical mediators of immune homeostasis. The co-stimulatory molecule CD27 is a marker of highly suppressive Tregs, although the role of the CD27-CD70 receptor-ligand interaction in Tregs is not clear. Here we show that after prolonged in vitro stimulation, a significant proportion of human Tregs gain stable CD70 expression while losing CD27. The expression of CD70 in expanded Tregs is associated with a profound loss of regulatory function and an unusual ability to provide CD70-directed co-stimulation to TCR-activated conventional T cells. Genetic deletion of CD70 or its blockade prevents Tregs from delivering this co-stimulatory signal, thus maintaining their regulatory activity. High resolution targeted single-cell RNA sequencing of human peripheral blood confirms the presence of CD27-CD70+ Treg cells. These findings have important implications for Treg-based clinical studies where cells are expanded over extended periods in order to achieve sufficient treatment doses.

Be cautious of "complex hydrocele" on ultrasound in young men.

Hydrocele is the most common benign cause of painless scrotal enlargement and only very rarely can be reactive to an underlying testicular tumor. We present the case of a healthy young man, complaining of mild left scrotal discomfort and swelling. Physical examination revealed a non-tender fluctuant left scrotum and serum tumor markers were normal. Scrotal ultrasonography (US) showed a normal right hemiscrotum and testicle and a fluid collection among thickened irregular septations in the left hemiscrotum, a finding which was considered as a complex hydrocele. Intraoperatively the presumed "complex hydrocele" was in fact a multicystic testicular tumor. We proceeded with orchiectomy through the scrotal incision and pathology revealed a mixed germ cell tumor of the testis consisting of cystic teratoma, in situ germ cell neoplasia unclassified (IGCNU) and Sertoli cell tumor. This is the first reported case of this type of testis tumor presenting as complex hydrocele. The aim of this case presentation is to underline the need for an accurate preoperative diagnosis in cases of suspected scrotal pathology in young males.

'Mini' U6 Pol III promoter exhibits nucleosome redundancy and supports multiplexed coupling of CRISPR/Cas9 effects.

RNA polymerase III (Pol III) promoters express short non-coding RNAs and have been adopted for expression of microRNA, interference RNA, and CRISPR single guide RNA (sgRNA). Vectors incorporating H1 and U6 Pol III promoters are being applied for therapeutic genome editing, including multiplexed CRISPR/Cas9 effects. We report a nucleosome-depleted, minimal U6 promoter, which when embedded within lentiviral long terminal repeat (LTR) regions, supports high level transcriptional activity. Furthermore, duplex minimal H1 & U6 promoters transcribed dual sgRNAs for simultaneous disruption of T cell receptor (TCR) and human leukocyte antigen (HLA) molecules, supporting efficient generation of 'universal' CAR T cells.

Human Mesenchymal Stromal Cells Engineered to Express Collagen VII Can Restore Anchoring Fibrils in Recessive Dystrophic Epidermolysis Bullosa Skin Graft Chimeras.

Recessive dystrophic epidermolysis bullosa (RDEB) is a debilitating genodermatosis caused by loss-of-function mutations in COL7A1 encoding type VII collagen (C7), the main component of anchoring fibrils at the dermal-epidermal junction. With no curative treatments presently available, retrovirally transduced autologous epidermal grafts and intradermal lentivirally engineered fibroblast injections are being investigated. Alternative approaches aim to infuse allogeneic mesenchymal stromal cells (MSCs) to provide a more generalized treatment for RDEB. We investigated whether healthy human MSCs could be engineered to overexpress C7 and correct RDEB in a human:murine chimeric model. Initially, engineered MSCs incorporated ex vivo into RDEB grafts, their presence confirmed by fluorescence in situ hybridization, revealed recovery of function of the dermal-epidermal junction with no signs of blister formation. Importantly, the detection of anchoring fibrils by transmission electron microscopy corroborated structural recovery. Next, MSCs cotransduced to express C7 and luciferase were delivered intradermally into grafted RDEB skin, resulting in localized MSC persistence with deposition of de novo C7 at the site. Notably, C7 expression was sufficient to restore anchoring fibril density to normal levels. In contrast, intravenously injected engineered MSCs were undetectable within grafts and lacked anchoring fibril reconstitution. Our data suggest that although localized correction may be achievable using engineered MSCs, strategies for systemic administration require further modeling.

Safety and early efficacy outcomes for lentiviral fibroblast gene therapy in recessive dystrophic epidermolysis bullosa.

BACKGROUNDRecessive dystrophic epidermolysis bullosa (RDEB) is a severe form of skin fragility disorder due to mutations in COL7A1 encoding basement membrane type VII collagen (C7), the main constituent of anchoring fibrils (AFs) in skin. We developed a self-inactivating lentiviral platform encoding a codon-optimized COL7A1 cDNA under the control of a human phosphoglycerate kinase promoter for phase I evaluation.METHODSIn this single-center, open-label phase I trial, 4 adults with RDEB each received 3 intradermal injections (~1 × 106 cells/cm2 of intact skin) of COL7A1-modified autologous fibroblasts and were followed up for 12 months. The primary outcome was safety, including autoimmune reactions against recombinant C7. Secondary outcomes included C7 expression, AF morphology, and presence of transgene in the injected skin.RESULTSGene-modified fibroblasts were well tolerated, without serious adverse reactions or autoimmune reactions against recombinant C7. Regarding efficacy, there was a significant (P < 0.05) 1.26-fold to 26.10-fold increase in C7 mean fluorescence intensity in the injected skin compared with noninjected skin in 3 of 4 subjects, with a sustained increase up to 12 months in 2 of 4 subjects. The presence of transgene (codon-optimized COL7A1 cDNA) was demonstrated in the injected skin at month 12 in 1 subject, but no new mature AFs were detected.CONCLUSIONTo our knowledge, this is the first human study demonstrating safety and potential efficacy of lentiviral fibroblast gene therapy with the presence of COL7A1 transgene and subsequent C7 restoration in vivo in treated skin at 1 year after gene therapy. These data provide a rationale for phase II studies for further clinical evaluation.TRIAL REGISTRATIONClincalTrials.gov NCT02493816.FUNDINGCure EB, Dystrophic Epidermolysis Bullosa Research Association (UK), UK NIHR Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust and King's College London, and Fondation René Touraine Short-Exchange Award.

Urothelial neoplasm in a 19-year-old male patient with urine discoloration, negative lab, and imaging workup: Should we investigate the findings or the symptom?

With few cases of PUNLMPs in young adults being reported in the literature, we hope to raise clinical awareness of prompt and effective diagnosis, while maintaining a high index of suspicion among health professionals. Even in the absence of red blood cells in the urine and subsequent negative imaging workup, clinicians should not delay performance of diagnostic cystoscopy.

Incidental finding of Zinner syndrome in a Greek military recruit: a case report of a rare clinical entity.

BACKGROUND: Zinner syndrome represents a rare congenital malformation of the urinary tract. It comprises a constellation of Wolffian duct anomalies and is almost exclusively encountered as a classic triad of seminal vesicle cysts, ejaculatory duct obstruction and renal agenesis. Patients can be either asymptomatic or symptomatic. Recently, minimally invasive surgical techniques have emerged, superseding traditional surgery for select symptomatic cases. Our case highlights the finding of a rare clinical syndrome that was incidentally detected during a routine mass screening of military recruits in the Greek Armed Forces. CASE PRESENTATION: Herein, we present a case of a 19-year-old male who reported having a solitary right kidney when examined in a military training center of Northern Greece. No additional clinical information was available; thus, referral to a tertiary urology department for further investigation ensued. Imaging studies, namely, computed tomography and magnetic resonance imaging, revealed left renal aplasia, multiple left seminal vesicle cysts, and ejaculatory duct obstruction. Laboratory values and urinalysis were within normal range. Semen analysis was significant for cryptozoospermia. Our patient remained asymptomatic during the entire hospitalization. Long-term follow-up was recommended. Nevertheless, he declined further investigation and sought treatment in a private practice setting. CONCLUSIONS: This article aims to present the incidental diagnosis of a rare syndrome in a military setting. Population screening conducted in the armed forces permits the identification of undiagnosed diseases that warrant further investigation. To the best of our knowledge, this was the first report of Zinner syndrome in a military recruit and the second case cited of a Greek patient in the published literature. Regular follow-up is the key to timely intervention in conservatively managed cases.

Emerging CRISPR/Cas9 applications for T-cell gene editing.

Gene editing tools are being rapidly developed, accelerating many areas of cell and gene therapy research. Each successive gene editing technology promises increased efficacy, improved specificity, reduced manufacturing cost and design complexity; all of which are currently epitomised by the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein (Cas9) platform. Since its conceptualisation, CRISPR-based gene editing has been applied to existing methodologies and has further allowed the exploration of novel avenues of research. Implementation of CRISPR/Cas9 has been instrumental to recent progress in the treatment of cancer, primary immunodeficiency, and infectious diseases. To this end, T-cell therapies have attempted to harness and redirect antigen recognition function, and through gene editing, broaden T-cell targeting capabilities and enhance their potency. The purpose of this review is to provide insights into emerging applications of CRISPR/Cas9 in T-cell therapies, to briefly address concerns surrounding CRISPR-mediated indel formation, and to introduce CRISPR/Cas9 base editing technologies that hold vast potential for future research and clinical translation.

Vesicouterine Fistula (VUF) as a Rare Urogenital Complication Managed with Delayed Surgical Repair: A Case Report and Review of the Literature.

Vesicouterine fistula (VUF) represents a rare urogenital complication. It is considered to be the least common type of urogenital fistulas. Iatrogenic reasons have been shown to be the most prominent cause, with lower segment caesarean section accounting for approximately two-thirds of the cases. The highest incidence concerns young females of reproductive age. VUF can present with clinical symptoms varying from cyclic hematuria, amenorrhea, and vaginal leakage of urine to secondary infertility and first-trimester abortion. Quality of life (QoL) for patients having this pathology is strongly affected due to the psychological burden. Surgical excision of the fistula remains the mainstay of treatment, as less than 5% of patients respond to conservative therapy. Recently laparoscopic and robotic-assisted VUF repair started gaining ground with comparable results to open surgery. Herein, we presented the successful delayed surgical repair of VUF in a 32-year-old female patient. A review of the published literature was also performed, summarizing all the available evidence regarding this rare clinical entity.