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A 75-year-old man was referred to our urology service with painless haematuria. The delayed phase on a subsequent computed tomography (CT) abdomen and pelvis showed a filling defect in the left renal pelvicalyceal system, suspicious for a transitional cell carcinoma. The patient underwent ureteroscopic biopsy suggestive of a papillary neoplasia, before progressing to a laparoscopic radical left nephrouretectomy. Final histology revealed a fumarate hydratase-deficient renal cell carcinoma with clear margins. The patient was subsequently referred for genetic counselling.

A 55-year-old male presented to our emergency department with haematuria and abdominal pain. Investigations including a computed tomography (CT) scan revealed an intraluminal filling defect within the left collecting system, consistent in appearance with blood clot. With an initial working diagnosis of upper tract urothelial cell carcinoma, he was discharged with plans for an urgent cystoscopy and ureteroscopy. He subsequently represented with ongoing frank haematuria, anasarca, dropping haemoglobin and new right collecting system blood clot. Subsequent investigations showed that the patient had acquired haemophilia A resulting in the episodes of haematuria, highlighted after an elevated activated partial thromboplastic time prompted a thrombophilia screen. The patient was subsequently treated with factor eight inhibitor bypass activity, corticosteroids and cyclophosphamide.

The number of Australian patients undergoing ventral hernia repair has seen a significant increase in the last twenty years. With the obesity epidemic, the general surgeon is frequently seeing patients with hernias and significant abdominal aprons and is being asked to address this at the time of the hernia repair. This can be performed utilising a general surgery and plastic surgery team, but there may be some advantages to general surgeon being able incorporate this into their practice. We present our approach to patients undergoing ventral hernia repair and simultaneous panniculectomy (VHR + PAN) by a single general surgeon. Data were analysed from a single surgeon’s experience performing VHR + PAN at the same operation. Data were collected prospectively from 2009 to 2020. 146 cases of patients undergoing VHR + PAN were identified and included in this study. The mean age of patients undergoing VHR + PAN was 58 years. The mean BMI was 35, with 59% of patients losing weight loss prior to surgery. 66% of patients had a hernia repair with biosynthetic mesh and 91% of patients had retro-rectus or pre-peritoneal mesh approach to the repair. 42% of patients had a post-operative complication with 80.6% of these being related to surgical-site occurrences. Other complications included gastrointestinal (14%), respiratory (13%) and venous thromboembolism, such as a deep vein thrombus or pulmonary embolism (6%). There were 2 deaths in the series (1.3%). The hernia recurrence rate was 6%. Simultaneous PAN is possible in patients with an abdominal apron who are undergoing VHR, with an acceptable risk of SSOs and other complications. This technique provides excellent exposure and with appropriate training is well within the remit of the general surgeon. This may save further operative management in the future and can offer patients improved self-esteem, mobility, and independence. Patient optimisation is key, paying careful attention to pre-operative weight loss, diabetic control, smoking cessation and respiratory function. VHR + PAN is an important technique that should be in the repertoire of all abdominal wall reconstruction units.

Transposable elements (TEs) are a reservoir of new transcription factor binding sites for protein-coding genes1–3. Developmental programs that activate TE-derived regulatory elements could, in principle, manifest in lineage-specific TE mobility. While somatic LINE-1 (L1) retrotransposon insertions have been detected in human neurons4–6, the impact of L1 insertions on neurodevelopmental gene regulation, and whether L1 mobility is restricted to certain neuronal lineages, is unknown. Here, we reveal programmed L1 activation by SOX6, a transcription factor critical for parvalbumin (PV+) interneuron development7–9. PV+ neurons harbor unmethylated and euchromatic L1 promoters, express L1 mRNA, and permit L1 transgene mobilization in vivo. Elevated L1 expression in adult dentate gyrus PV+ neurons is however attenuated by environmental enrichment. Nanopore sequencing of PV+ neurons identifies unmethylated L1 loci providing alternative promoters to core PV+ neuron genes, such as CAPS2. These data depict SOX6-mediated L1 activation as an ingrained component of the mammalian PV+ neuron developmental program.

The retrotransposon LINE-1 (L1) is central to the recent evolutionary history of the human genome and continues to drive genetic diversity and germline pathogenesis. However, the spatiotemporal extent and biological significance of somatic L1 activity are poorly defined and are virtually unexplored in other primates. From a single L1 lineage active at the divergence of apes and Old World monkeys, successive L1 subfamilies have emerged in each descendant primate germline. As revealed by case studies, the presently active human L1 subfamily can also mobilize during embryonic and brain development in vivo. It is unknown whether nonhuman primate L1s can similarly generate somatic insertions in the brain. Here we applied approximately 40× single-cell whole-genome sequencing (scWGS), as well as retrotransposon capture sequencing (RC-seq), to 20 hippocampal neurons from two rhesus macaques (Macaca mulatta). In one animal, we detected and PCR-validated a somatic L1 insertion that generated target site duplications, carried a short 5′ transduction, and was present in ∼7% of hippocampal neurons but absent from cerebellum and nonbrain tissues. The corresponding donor L1 allele was exceptionally mobile in vitro and was embedded in PRDM4, a gene expressed throughout development and in neural stem cells. Nanopore long-read methylome and RNA-seq transcriptome analyses indicated young retrotransposon subfamily activation in the early embryo, followed by repression in adult tissues. These data highlight endogenous macaque L1 retrotransposition potential, provide prototypical evidence of L1-mediated somatic mosaicism in a nonhuman primate, and allude to L1 mobility in the brain over the past 30 million years of human evolution.

Amyloidosis of the lower genitourinary tract is an extremely rare condition and often mimics urothelial malignancy. In this paper, we report two cases of ureteral and urethral amyloidosis that initially presented as urothelial carcinoma and were successfully treated with laparoscopic nephroureterectomy and trans-urethral resection, respectively. This disease, with its various atypical presentations, presents a diagnostic challenge to urologists. Awareness is important as excision can be curative, and presence of systemic disease must be excluded.

A recent study proposed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hijacks the LINE-1 (L1) retrotransposition machinery to integrate into the DNA of infected cells. If confirmed, this finding could have significant clinical implications. Here, we apply deep (>50×) long-read Oxford Nanopore Technologies (ONT) sequencing to HEK293T cells infected with SARS-CoV-2 and do not find the virus integrated into the genome. By examining ONT data from separate HEK293T cultivars, we completely resolve 78 L1 insertions arising in vitro in the absence of L1 overexpression systems. ONT sequencing applied to hepatitis B virus (HBV)-positive liver cancer tissues located a single HBV insertion. These experiments demonstrate reliable resolution of retrotransposon and exogenous virus insertions by ONT sequencing. That we find no evidence of SARS-CoV-2 integration suggests that such events are, at most, extremely rare in vivo and therefore are unlikely to drive oncogenesis or explain post-recovery detection of the virus., Graphical abstract, In response to a recent claim that SARS-CoV-2 can be incorporated into human DNA by LINE-1 retrotransposon proteins, Smits et al. apply long-read DNA sequencing to cultured HEK293T cells infected with SARS-CoV-2. They find no evidence for genomic integration of the virus, despite demonstrated availability of the LINE-1 protein machinery.

SUMMARYA recent study proposed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hijacks the LINE-1 (L1) retrotransposition machinery to integrate into the DNA of infected cells. If confirmed, this finding could have significant clinical implications. Here, we applied deep (>50×) long-read Oxford Nanopore Technologies (ONT) sequencing to HEK293T cells infected with SARS-CoV-2, and did not find the virus integrated into the genome. By examining ONT data from separate HEK293T cultivars, we completely resolved 78 L1 insertions arisingin vitroin the absence of L1 overexpression systems. ONT sequencing applied to hepatitis B virus (HBV) positive liver cancer tissues located a single HBV insertion. These experiments demonstrate reliable resolution of retrotransposon and exogenous virus insertions via ONT sequencing. That we found no evidence of SARS-CoV-2 integration suggests such events are, at most, extremely rarein vivo, and therefore are unlikely to drive oncogenesis or explain post-recovery detection of the virus.

The number of Australian patients undergoing ventral hernia repair has seen a significant increase in the last twenty years. With the obesity epidemic, the general surgeon is frequently seeing patients with hernias and significant abdominal aprons and is being asked to address this at the time of the hernia repair. This can be performed utilising a general surgery and plastic surgery team, but there may be some advantages to general surgeon being able incorporate this into their practice. We present our approach to patients undergoing ventral hernia repair and simultaneous panniculectomy (VHR + PAN) by a single general surgeon.Data were analysed from a single surgeon's experience performing VHR + PAN at the same operation. Data were collected prospectively from 2009 to 2020. 146 cases of patients undergoing VHR + PAN were identified and included in this study.The mean age of patients undergoing VHR + PAN was 58 years. The mean BMI was 35, with 59% of patients losing weight loss prior to surgery. 66% of patients had a hernia repair with biosynthetic mesh and 91% of patients had retro-rectus or pre-peritoneal mesh approach to the repair. 42% of patients had a post-operative complication with 80.6% of these being related to surgical-site occurrences. Other complications included gastrointestinal (14%), respiratory (13%) and venous thromboembolism, such as a deep vein thrombus or pulmonary embolism (6%). There were 2 deaths in the series (1.3%). The hernia recurrence rate was 6%.Simultaneous PAN is possible in patients with an abdominal apron who are undergoing VHR, with an acceptable risk of SSOs and other complications. This technique provides excellent exposure and with appropriate training is well within the remit of the general surgeon. This may save further operative management in the future and can offer patients improved self-esteem, mobility, and independence. Patient optimisation is key, paying careful attention to pre-operative weight loss, diabetic control, smoking cessation and respiratory function. VHR + PAN is an important technique that should be in the repertoire of all abdominal wall reconstruction units.

Level of evidence: IV