Background: The aim of this paper is to discuss the impact of COVID-19 on patients with urological malignancies  and to review the available recommendations reported in the literature. Methods: A review was performed, through the PubMed database, regarding available recommendations reported in the literature, to identify studies examining the impact of COVID-19 on treatment and clinical outcomes  for uro-oncological patients. Results: The COVID-19 pandemic dramatically changed the urological guidelines and patients’ access to screening programs and follow-up visits. Great efforts were undertaken to guarantee treatments to high-risk patients although follow up was not always possible due to recurrent surges, and patients with lower risk cancers had to wait for therapies. Conclusions: Physically and mentally, uro-oncological patients paid a heavy price during the COVID-19 pandemic. Long term data on the “costs” of clinical decisions made during the COVID-19 pandemic are still to be revealed and analyzed. As of 1 December 2022, 6.63 million fatalities and 643 million cases of COVID-19 had been documented globally . Since tThis paper is the second in a series of literature reviews regarding urology and public health that our research group has completed .A narrative review of available recommendations reported in the literature regarding the impact of COVID-19 on patients with uro-oncologic cancers was performed.The following search terms were used to identify eligible articles through the PubMed database:(“COVID-19” OR “SARS-CoV-2” OR COVID OR Coronavirus) AND .The search was limited to articles written in English, published from the beginning of the pandemic (February 2020)) up until the search was performed (December 2022), and no other filters were applied.Bladder cancer (BC);Prostate cancer (PCa);Renal cell carcinoma (RCC);Upper tract urothelial carcinoma (UTUC);Penile cancer and Testicular cancer.Articles investigating the impact of COVID-19 on treatment and clinical outcomes  of patients with:Manuscripts that did not investigate the impact of COVID-19 on the treatment and clinical outcomes of patients with uro-oncologic cancers were excluded.Two researchers (F.G. and C.A.) performed data extraction from the included articles and reported the results in an Excel worksheet. One author (F.G.) extracted data from the included studies, and the second author (C.A.) checked the extracted data. Disagreements were resolved by a consensus-based discussion between the two review authors (F.G. and C.A.); if agreement could not be reached, a third author (N.F.) was scheduled to inter-vene.The research findings are reported by uro-oncologic tumor type as follows.With the explosive increase of patients with COVID-19, unprecedented limits were placed to stop the spread of SARS-CoV-2 and to reorganize the healthcare system and prevention campaigns as a whole . The comThe first year of the COVID-19 pandemic has changed our urologic practice dramatically for both patients with benign and malignant diseases ,30. The Pharmacological treatments for prostate cancer include androgen deprivation therapy (ADT). In recent years, articles on how ADT can help to prevent or lessen the severity of COVID-19 were published ,38,39. BBernstein et al.  conducteHematuria is a worrisome symptom and can be a sign of bladder cancer. During COVID-19, its management is even more challenging. Although there is no widely acknowledged standard procedure, visible hematuria always needs to be investigated because its presence indicates a risk of roughly 20.4% malignancy, compared to 2.7% in the case of microscopic hematuria ,44,45. ACystoscopy is still the gold standard for the diagnosis of bladder cancer, although in the worst months of the COVID-19 pandemic, cystoscopy appointments were cancelled for most patients. An important factor delaying diagnosis or therapy may be a patient’s psychological state and fear of contracting COVID-19. Delaying routine treatment could inevitably result in progression or recurrence for patients with bladder cancer or suspected bladder cancer who require long-term surgical management and have locally advanced tumors or rapid tumor growth. Urologists should not stop screening since bladder cancer has a far higher fatality rate than COVID-19, which can be as high as 52% .Bladder cancer can be classified in four categories:1. Low-grade non–muscle-invasive bladder cancer (NMIBC)NMIBC, or low-grade non-muscle-invasive bladder cancer, is a condition that is often not aggressive. Active surveillance (AS) is a key management strategy for recurrent low- and intermediate-risk NMIBCs, which have long-term BC-specific death rates of approximately 1–2%. If the patient is recurrence-free, guidelines recommend discharge after 12 or 60 months .2. High-grade NMIBCIn high-grade NMIBC, 15–40% of patients proceed to muscle invasion/metastases, and 10–20% of people may pass away from BC. Radical cystectomy (RC) and immunotherapy with bacillus Calmette-Guérin (BCG) are the main therapies . Up to 83. Muscle-invasive bladder cancerSeveral studies showed that delays between neoadjuvant chemotherapy and radical chemotherapy were connected to poor survival results, while another research showed that delays were connected to upstaging .4. Advanced or metastatic BCFor the majority of patients with advanced or metastatic BC, cytotoxic chemotherapy with or without immunotherapy continued to be the preferred course of action.The European Association of Urology (EAU) updated their guidelines according to the current COVID-19 pandemic . DelayinCT urography is still essential to investigate possible upper urinary tract urothelial cancer (UTUC). Focused research on UTUC has shown that treatment rescheduling resulted in poorer prognostic outcomes overall, including worse pathologic staging, the presence of carcinoma in situ (CIS), tumoral infiltration, and other factors ,54. The The EAU advised that regimens of intravesical bacillus Calmette-Guérin treatment lasting more than a year might be safely stopped for patients with high-risk NMIBC during the COVID-19 pandemic. Moon et al.  reportedDespite the guidelines’ updates, during the COVID-19 pandemic, routine oncological follow up controls and screening procedures and elective surgeries were deprioritized . For indThe expression of the ACE2 and transmembrane protease serine 2 (TMPRSS2) receptors is upregulated in the urinary system, particularly in the kidneys, designating these organs as crucial targets for SARS-CoV-2 infection. Although mesangial cells and glomerular endothelial cells do not express ACE2 or TMPRSS2, they are expressed by proximal tubular cells and, to a lesser extent, podocytes ,63. AKI Patients with localized renal cell carcinoma (RCC) are often treated with resection, radiographic monitoring, and adjuvant immunotherapy, depending on the tumor stage. During imaging procedures, patients under radiographic monitoring may be exposed to COVID-19 ,67. PatiAccording to some studies, immune checkpoint inhibitor therapy exposure may be a separate risk factor for the emergence of a more severe clinical course of COVID-19 infection. This may be because immune checkpoint inhibitors exposure may cause immune-related pulmonary toxicities and increased T-cell cytokine production . ContrarSome retrospective investigations have found no correlation between acquiring immune checkpoint inhibitors and having a COVID-19 infection, and no increase in the severity or mortality of the infection . No dataIn the face of COVID-19, doctors may have suggested de-escalating therapy and monitoring according to the EAU guidelines . During Apparently a delay of less than 3 months in surgical treatment of patients with a diagnosis of T1b or T2b renal cell carcinoma did not significantly increase the risk of tumor progression and change of surgical approach . Wai-ShuOther studies reported a significant decrease in diagnostic procedures and treatment, the consequences of which are still to be investigated ,79. GiveMoreover, Khene et al.  demonstrPenile cancer is a rare condition, representing 1% of all cancers in men. The highest incidence is between 60 and 80 years of age. Due to the low incidence of penile cancers, few resources were invested during the COVID-19 pandemic . In ordeOn the other hand, delaying penile cancer therapy might cause the underlying tumor’s disease to advance to the point where organ-preserving surgery may no longer be an option for treating the disease since penile cancer patients typically wait too long to be attended . ConsensTesticular cancer is an uncommon neoplasm that accounts for 1–2% of tumors in men. In most cases, it is curable, but it has the highest incidence in young adults (14–34 years) . One tesStudies conducted before the COVID-19 pandemic have shown a significant increase of tumor progression in 30 days between early orchiectomy group and delayed orchiectomy group . RadicalSeminomas are usually radiosensitive and chemo-sensitive, while non-seminomas are less sensitive to radiation. In case of metastatic disease, chemotherapy and surgery are usually required ,88,89.There is not as much data on the impact of postponing surgical therapy due to COVID-19 for testicular cancer. According to a recent analysis, testicular cancer patients would benefit from minimizing delays and their management should be prioritized .The healthcare system is under tremendous strain because of the COVID-19 epidemic. As of 1 December 2022, 6.63 million fatalities and 643 million cases of COVID-19 had been documented globally . It is wThe diagnosis of cancer has a great psychological burden on patients. During the COVID-19 pandemic, it was likely magnified due to uncertainty and treatment delays. Physicians had to reallocate resources and prioritized treatment as the guidelines suggested, considering age, comorbidities, symptoms, and life expectancy. Physically and mentally, uro-oncological patients paid a heavy price during the COVID-19 pandemic. Finally, despite scientific societies efforts to rewrite guidelines for the pandemic period, all oncology patients suffered from delayed controls, treatments and diagnosis. Long term data on the “costs” of such decisions are still to be revealed and analyzed.


Primary CNS tumors are rare. Coexistence of two glial tumors of different histological origins in the same patient is even rarer. Here we describe two unique cases of coexisting distinct glial tumors in opposite hemispheres.Patient 1 is a 38-year-old male who presented with a seizure in February/2016. MRI showed a left parietal and a right frontal infiltrating nonenhancing lesions. Both lesions were resected revealing an oligodendroglioma WHO grade-2 and an astrocytoma WHO grade-2. Patient 2 is a 34-year-old male who presented with a seizure in November/2021. MRI showed a left frontal and a right mesial temporal lobe infiltrating nonenhancing lesions. Both lesions were resected revealing an oligodendroglioma WHO grade-2 and a diffuse low-grade glioma, MAPK pathway-altered (BRAF V600E-mutant). Patient 1 underwent adjuvant treatment. Both patients are without recurrence to date.Two histologically distinct glial tumors may coexist, especially when they are non-contiguous. Pathological confirmation of each lesion is imperative for appropriate management. We highlight the different management of gliomas based on the new CNS WHO 2021 classification compared to its 2016 version, based on NCCN guidelines. Although more molecular markers are being incorporated into glioma classification, their clinical impact of it is yet to be determined. Primary Central Nervous System (CNS) tumors are rare and account for about 2% of all cancers with an overall incidence of 22 per 100,000 population –29. HereA 38-year-old male presented to the ED after experiencing a new onset GTC seizure in February 2018. MRI brain was eventually obtained revealing two infiltrating, expansile, and non-contiguous T2-FLAIR hyperintense lesions on the left parietal and right frontal lobes. Faint enhancement was seen in the posterior aspect of the left temporal lesion Figure 1He underwent a craniotomy and GTR of the left parietal lesion on 6/2018. Pathology revealed oligodendroglioma, WHO grade 2, IDH-mutant, 1p/19q-codeleted. One month later, he underwent a second craniotomy and GTR of the right frontal lesion. Pathology revealed an astrocytoma, WHO grade 2, IDH-mutant, ATRX-mutant, and 1p/19q-intact Figure 2The patient did well postoperatively and remains seizure-free while on antiepileptic monotherapy. He developed chronic right homonymous hemianopsia but is otherwise cognitively and physically intact. The decision was made to treat the astrocytic right frontal lesion with intensity-modulated radiation therapy (IMRT)  followed by temozolomide for a total of 12 cycles to treat both pathologies. He is currently doing well without recurrence or worsening neurological symptoms at his last follow-up on 1/11/2022. He continues to work three jobs and is excited about getting married in February.A 34-year-old right-handed male presented to the emergency department (ED) in September 2021 after new-onset episodes of expressive aphasia, each lasting less than 2 minutes. While in the ED, he developed two generalized tonic-clonic (GTC) seizures. MRI brain demonstrated two expansile, non-enhancing, and non-contiguous T2-FLAIR hyperintense lesions on the left frontal and right mesial temporal lobes Figure 3He underwent an uncomplicated awake craniotomy and gross total resection (GTR) of the left frontal lesion with intraoperative MRI. Pathology was consistent with oligodendroglioma, WHO grade 2, IDH-mutant, 1p/19q-codeleted.After he recovered from the first surgery, he underwent a right temporal craniotomy and subtotal resection of the contralateral lesion on the right mesial temporal lobe. Morphologic and molecular findings from this specimen were most suggestive of diffuse low-grade glioma, MAPK pathway altered as the tumor showed evidence of BRAF mutation (V600E). The tumor is notably IDH wildtype, H3 wildtype, 1p/19q not co-deleted, and no evidence of CDKN2A deletion, indicating a favorable prognosis Figure 4The patient did well after both surgeries and remained seizure-free while on monotherapy antiepileptic. He remained both clinically and radiographically stable at his 6-month follow-up visit. He is currently doing well without recurrence; the most recent follow-up was on 6/7/2022. He works full-time as an engineer but has transitioned to an office job as he had trouble with extreme temperatures. He feels back to his baseline with infrequent memory problems.Here we describe two unique cases of co-existing glial tumors from distinct cellular lineages on opposite brain hemispheres. Both patients initially presented following new-onset seizures. They both underwent two separate craniotomies for maximal safe resection of each of the lesions. Both patients had coexistence of oligodendroglial and an astrocytic tumor, one in each hemisphere.To our knowledge, this is the first report of co-existing glial tumors from distinct histologic and molecule profiles on opposite brain hemispheres. It is critical to recognize this as part of the differential diagnosis when evaluating patients with two discrete, non-contiguous lesions, as historically  these may have been misdiagnosed as gliomatosis and/or multifocal pathologies. A literature review conducted by Tunthanathip et al. identified 6 cases of coexisting intracranial tumors and summarized the author’s experiences. They then identified 65 similar cases described in the literature. They noted that the most common association was a meningioma and pituitary adenoma, and that meningioma was present in most of their reported cases . AdditioThe strikingly different mutation and methylation profiles observed in the two tumors in each case 4 suggesAnother important point is the impact of the new 2021WHO classifications on management when compared to the 2016 WHO classification , 34. PriThis manuscript describes two rare cases of coexisting glial tumors in opposite brain hemispheres, and it illustrates the differences in glioma classification comparing the 2021 WHO classification to its previous 2016 version. It also highlights the difference in the management of brain tumors based on an integrated diagnosis strategy as recommended by NCCN guidelines.The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.FP and MK contributed to the conception and design of the case report. IS wrote the first draft of the manuscript. FP, MK, and IS wrote sections of the manuscript. DC provided histologic imaging. MS contributed to the acquisition of the data, its analysis, and interpretation. All authors contributed to the manuscript revision, read, and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


We describe the case of a 7-year-old girl with anti-leucine-rich glioma-inactivated 1 (anti-LGI1) antibodies (Abs) who presented with isolated epileptic seizures. Her refractory focal seizures did not respond to anti-seizure medicines but responded rapidly to immunotherapy. She remained seizure-free at 2 years follow-up. Reviewing the literature, isolated epileptic seizures have not been reported as the phenotype of anti-LGI1 autoimmunity in children. Our study indicated that screening for anti-LGI1 Abs is necessary for children with severe and/or drug-resistant new-onset focal epileptic seizures. Anti-leucine-rich glioma-inactivated 1 (anti-LGI1) encephalitis is the second most frequent type of autoimmune encephalitis in adults . Anti-LGI1 Abs was detected at a titer of 1:30  was normal. Electroencephalography (EEG) revealed slow background activity  and epil of 1:30  in the sOxcarbazepine (OXC) was administered to control frequent seizures after admission (17th day after onset), with poor response. The etiology of the patient’s epilepsy is important for treatment. The six etiologies of epilepsy include structural, genetic, infectious, metabolic, and immune disorders, and also an unknown group. Structural etiology was excluded by the normal brain MRI. The patient was previously healthy, with normal developmental milestones, and all metabolic examinations were normal, hence metabolic etiology was excluded. She had acute onset with no family history of seizures, which did not support genetic epilepsy. Infectious etiology was excluded for the absence of infection symptoms, normal CSF test results, and infectious agents. Since she had an acute onset condition with positive anti-LGI1 antibody in serum and slow background activity in EEG, autoimmune epilepsy should be considered. Hence, we tried immunotherapy. Immunotherapy was initiated on the 21st day after onset. Intravenous immunoglobulin  was administered, and the number of seizures significantly decreased. On the 25th day after onset, high-dose intravenous methylprednisolone (20 mg/kg) was administered once a day for 3 days, followed by oral prednisolone treatment for 6 months. The seizure frequency gradually decreased 2 days after intravenous methylprednisolone, and the seizures disappeared. One month later, serum anti-LGI1 Abs were negative . The sloAntibodies directed against LGI1 were discovered in 2010. Anti-LGI Abs are recognized as one of the anti-cell surface Abs associated with autoimmune encephalitis. Their presence is associated with characteristic symptoms such as faciobrachial dystonic seizures (FBDS), temporal lobe seizures, memory dysfunction, hyponatremia, and neuropsychiatric symptoms. Association with tumor occurs in up to 11–13% of cases with anti-LGI1 Abs, which has been mostly reported in adults. More than 80% of the adult patients with anti-LGI1 encephalitis had epileptic seizures. Focal epileptic seizures were also prominent. Most patients had frequent seizures and responded poorly to anti-seizure medicines. However, Status epilepticus (SE) is rare.Recently, only a small number of children with this condition have been reported. To date, there has not been a well-defined description of the clinical spectrum in children. Encephalitis is one of the most common clinical symptoms of pediatric LGI1 autoimmunity . With thFaciobrachial dystonic seizures are specific to anti-LGI1 encephalitis, although only in a minority of patients. FBDS are involuntary contractions lasting 1–2 s, are unilateral, and occur up to 100 times a day. FBDS are considered as non-epileptic episodes due to the common absence of ictal EEG abnormalities. However, the underlying mechanism of FBDS remains controversial. Some researchers found that the percentage of abnormal basal ganglia signals in patients with FBDS was significantly higher than in non-FBDS patients. Therefore, they thought that FBDS were related to the function of the basal ganglia, making them a type of movement disorder. FBDS present as high-frequency attacks (40 ± 17 times per day) with short episodes (2.1 ± 0.7 s) and are always unilateral , so theyThe attacks in our patient showed prominent unilateral motor seizures, but most lasted longer than 10 s, and the epileptic wave discharge on EEG during the episode did not display the features of typical FBDS. Few studies on FBDS in children have been conducted. Whether FBDS have different characteristics in children requires further investigation.We describe a pediatric case of isolated focal seizures associated with anti-LGI1 Abs that responded poorly to anti-seizure medicines but responded well to immunotherapy. This phenomenon has prompted the study of the role of autoimmunity in epileptic seizures. Immunity has been reported as one of the possible etiologies of new-onset epilepsy or established epilepsy of unknown etiology , 12. AmoCurrently, there are several criteria for selecting and sorting patients with putative autoimmune epilepsy. One is the Antibody Prevalence in Epilepsy (APE) score proposed by Dubey et al. . An APE Our study had several limitations. The patient was not subjected to proper cognitive tests during an acute episode or follow-up. Because the best assay technologies were not available to us at the time of our study, we could not perform assays such as end-point titer determination and tissue-based antibody assays. We will incorporate them in future cases.In summary, epileptic seizures may be isolated manifestations of LGI1 autoimmunity in children. For pediatric patients with severe and/or drug-resistant new-onset focal epileptic seizures, routine antineuronal antibody screening is recommended to avoid delay of immunotherapy and improve prognosis.15811076790@163.com; YuW, 13838393216@163.com.The datasets for this article are not publicly available due to concerns regarding participant/patient anonymity. Requests to access the datasets should be directed to W-HZ, Written informed consent was obtained from the individual(s), and minor(s)’ legal guardian/next of kin, for the publication of any potentially identifiable images or data included in this article.YiW drafted the manuscript and attended the patient. YuW did the follow-up with the patient. W-HZ and YuW edited the manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


To report a novel combining a 25-gauge retrobulbar needle with a built-in 30-gauge needle surgical technique for subfoveal perfluorocarbon liquid (PFCL) removal.Fourteen eyes of 14 patients who underwent subfoveal PFCL removal with a 25-gauge retrobulbar needle combined with a built-in 30-gauge needle were studied. The 30-gauge needle was inserted into the 25-gauge retrobulbar needle. The bent tip of the built-in 30-gauge needle was used to create a 30-gauge retinotomy at the farthest edge of the subfoveal PFCL droplet. Then, a flute cannula was used to aspirate the PFCL through the previously created retinotomy. The best-corrected visual acuity (BCVA) was determined, previous surgical history and post-operative complications were recorded.p = 0.006). Post-operative complications included a self-healing macular hole in one eye and vitreous hemorrhage in one eye. Post-operative optical coherence tomography confirmed removal of the subfoveal PFCL with restoration of the macular fovea.Fourteen cases were analyzed. Most eyes (92.85%) showed an improvement in BCVA after surgery. The mean change in the BCVA was −0.7 ± 0.72 logarithm of the minimum angle of resolution (logMAR) units (Combining a 25-gauge retrobulbar needle with a built-in 30-gauge needle to remove subfoveal PFCL is easy to perform and carries little potential risk of subretinal impairment. This method also provides relatively good macular contour with functional improvement. The application of perfluorocarbon liquid (PFCL) in intraocular surgery is well established . Its uniAlthough many adverse effects associated with subretinal PFCL retention have been reported, the existence of such tiny droplets will only be of concern for symptomatic patients. Extrafoveal PFCL usually does not migrate into the subfoveal space, nor does it cause significant complications. The long-term existence of subfoveal PFCL droplets may constitute a risk of retinal degeneration, gravity deformation, barrier effects, retinal pigment epithelium (RPE) and photoreceptor toxicity, which can induce irreversible glial proliferation, retinal damage and vision loss , 8. The Fourteen eyes of 14 patients who underwent subfoveal PFCL removal with a 25-gauge retrobulbar combined with a built-in 30-gauge needle between December 2017 and June 2021 were retrospectively evaluated. All surgeries were performed by the same experienced surgeon (PZ) at Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. This study adhered to the tenets of the Declaration of Helsinki. Ethics Committee approval was obtained from the Xinhua Hospital review board. Informed consent was obtained from all patients or their guardians, and possible complications of the procedure were explained.® PLC, Dunfermline, Scotland, United Kingdom), were also obtained. The BCVA was measured as the total number of letters on the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart when assessed at a starting distance of 4 m.Medical records containing information on demographics and previous surgical manipulations were obtained. Standard ophthalmological examination records, such as the pre-operative and final best-corrected visual acuity (BCVA), slit-lamp evaluation findings, intraocular pressure (IOP), follow-up duration, spectral domain optical coherence tomography (SD-OCT) findings , and ultrawide-field scanning laser ophthalmoscopy (UWF-SLO) imaging findings .For statistical convenience, the BCVA results were converted into logarithm of the minimum angle of resolution (logMAR) units for calculation. The Wilcoxon signed-rank test was used to determine the significance of any association between the pre-operative and post-operative BCVA. A ®, Zhejiang, China) with a built-in 30-gauge needle  was used to remove subfoveal PFCL droplets. An ophthalmic needle holder was used to pull out the 30-gauge needle and then insert it into the 25-gauge retrobulbar needle  was performed. A combined needle consisting of a 25-gauge retrobulbar needle  as the primary indication for the use of PFCL, including 5 cases of traumatic RD, 4 cases of recurrent RD, 1 case of exudative RD (ERD) caused by retinitis pigmentosa (RP), 1 case of hemorrhagic RD secondary to polypoidal choroidal vasculopathy (PCV) with massive subretinal hemorrhage, 1 case of tractional RD (TRD) caused by retinal capillary hemangioma (RCH), 1 case of combined ERD and TRD caused by familial exudative vitreoretinopathy (FEVR) and 1 case of TRD that lasted for 8 years after congenital cataract surgery. Since nearly all patients had complicated primary vitreoretinopathies, 9 of them had a history of multiple surgeries for RD, and the number of previous operations varied from 1 to 8. Only one patient mentioned central scotoma, which significantly improved after the operation. All other patients were asymptomatic, and retained subfoveal PFCL droplets were not detected until the first post-operative follow-up visit. The mean post-operative follow-up period was 17.43 ± 11.86 months, ranging from 6 to 48 months.p = 0.006). The mean change in the BCVA was −0.7 ± 0.72 logMAR units. In case 13, the patient had RD for 8 years after congenital cataract surgery. He underwent 8 operations before the subfoveal PFCL removal surgery because of recurrent RD. However, vitreous hemorrhage (VH) was found at his 1-month post-operative follow-up, and he underwent another PPV with silicone oil tamponade. Based on his underlying pathology and rapid progression, he had unsatisfactory visual outcomes.When comparing the last follow-up to pre-operative visual acuity, the BCVA was better in 13 eyes (92.85%) and worse in 1 eye (7.15%). The mean pre-operative BCVA was 1.62 ± 0.58 logMAR units, which improved to 0.92 ± 0.51 logMAR units after subfoveal PFCL removal at the last follow-up visit post-operatively  in 1 eye (case 7) and VH in 1 eye (case 13). No other intraoperative or post-operative complications  related to this PFCL removal technique were noted. Post-operative OCT confirmed removal of the subfoveal PFCL droplets a few days after surgery . Table 1Perfluorocarbon liquid is commonly used in complicated intraocular surgeries to improve the surgical management of vitreoretinal diseases . SpontanThe toxicity of subfoveal PFCL has been thoroughly studied both in animal experimental models and in humans . PFCL drDifferent surgical techniques to remove subfoveal PFCLs have been reported, and these techniques can be broadly classified based on either direct aspiration or indirect displacement. One approach is direct aspiration with a small-gauge cannula or needle, ranging from 25 to 50 G, –14 with Another approach is indirect displacement with or without removal of the PFCL. One method is to create a localized macular RD outside the fovea and gently perform subretinal infusion. However, direct flushing in the subretinal space may lead to damage to the RPE or photoreceptor cells, especially when saline solution is rapidly and forcefully injected. Full-thickness MH formation may be another potential operative complication of this procedure, and areas of retinal thinning overlying the PFCL droplets may rupture secondary to an unstable injection pressure, which is experience dependent , 17. TurAnother method is to create a site of temporary RD at the posterior pole and a retinotomy near the inferotemporal vessels, followed by fluid-air exchange. After these procedures, the patient is asked to maintain an upright position for a short period post-operatively to allow displacement of the PFCL droplets . HoweverSørensen et al. found that large expansion of the subretinal space and repeated subretinal injection of fluid can damage the RPE, while retinotomy and limited RPE damage are well tolerated. Surgical manipulation and instrumentation in the subretinal space involve a risk of mechanical RPE damage and visual function decline . Our tecAccording to previous studies, eyes with subfoveal PFCL have better visual outcomes after PFCL removal or displacement . AlthougThe most common complications of subfoveal PFCL removal surgery were RPE damage, subretinal hemorrhage, proliferation and MH formation . The majThere are limitations to our study, including the small sample size, limited follow-up period, and lack of a control group. A longer follow-up period is needed to further assess retinal morphological restoration, visual functional improvement and post-operative complications. Our results show that using a 25-gauge retrobulbar needle combined with a built-in 30-gauge needle to remove subfoveal PFCL seems to be a safe and effective technique with good visual outcomes and few potential complications.In conclusion, our technique combining a 25-gauge retrobulbar needle with a built-in 30-gauge needle might be useful for subfoveal PFCL displacement. This technique is easy to perform, achieves relatively good macular contour with functional improvement, and carries little risk of subretinal impairment. However, a longer follow-up observation period is required to examine the long-term anatomical and functional outcomes associated with this technique.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.This studies involving human participants were reviewed and approved by the Xinhua Hospital review board. Written informed consent was obtained from the minor(s)’ legal guardian/next of kin for the publication of any potentially identifiable images or data included in this article.PZ and JP: conceptualization and funding acquisition. YY and PZ: methodology. YY, HX, XZ, and WM: data curation and writing – original draft preparation. XW and HY: writing – review and editing. YW: supervision. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


To establish a nationwide epidemiological profile of transfusion-transmittable infection (TTI) markers among seemingly healthy blood donors to update policies required to ensure blood safety.A nationwide, cross-sectional study was designed to examine donor demographics and TTI prevalence during 2020 using data provided by the Ministry of Health, Saudi Arabia.Collectively, a total of 375,218 whole blood units were donated, of which 32,758 (8.7%) were excluded due to TTI-related risk. The exclusion was based on a positive nucleic acid amplification test (NAT) or seroreactivity to hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), human T-cell lymphotropic virus (HTLV-I/II), syphilis, or malaria. Notably, the central (37.6%) and southern (33%) regions were the epicenters of TTI-reactive blood donors. Hepatitis B virus markers accounted for 85.7% and were the overall most prevalent of TTI-positive donations, followed by HCV at 5.9% and syphilis at 5.6%. In particular, anti-HBc and HBsAg were most prevalent in the south, while HBV NAT was highest in the center.Hepatitis B virus, HCV, and syphilis carry the greatest risk of TTI in Saudi Arabia. Including HBsAg screening is a necessary precautious measure to maintain blood safety. Blood transfusion plays a pivotal role in the management of hemorrhage and other hematological diseases. In Saudi Arabia, the healthcare system is overseen by the Ministry of Health (MOH), which has authority over the 13 national provinces. Besides formulating healthcare policies, the MOH has been providing free healthcare services through governmental hospitals and blood donation centers since its inception. All blood donors undergo screening for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), hepatitis C virus anti-body (anti-HCV), human immunodeficiency virus antibodies (anti-HIV-1/-2), human T-cell lymphotropic virus-I and -II antibodies (anti-HTLV I/II), syphilis, and malaria. In addition, nucleic acid testing (NAT) is also performed for hepatitis B virus (HBV), HCV, and HIV-1/-2 on all blood donations to curtail the risk of infection transmission. Thanks to established quality blood screening protocols, the global and local residual risk of transfusion-transmissible infections (TTIs) has been reduced over tim. However, number of challenges have been recognized by the National Transformation Plan (NTP) of Vision 2030 including population growth, increased financial burden, and inconsistent statistical reports submitted by the fragmented administration of MOH’s healthcare institutes.  To tackle these concerns within the context of transfusion medicine, mitigation strategies to curtail TTIs are often influenced by local epidemiology and cost-effectiveness considerations. In addition, accurate statistical reporting can offer the chance of investigating the prevalence of TTI rates in the asymptomatic infectious phase of seemingly healthy blood donors who pose the greatest risk to blood safety.Approximately, an average of 325,847 whole blood units are annually collected from 128 governmental blood banks distributed among the Kingdom’s 13 province. In this report, we carried out a nationwide, cross-sectional study to analyze the frequency of TTI markers among seemingly asymptomatic blood donors in Saudi Arabia in 2020.Available literature on TTI prevalence in Saudi Arabia is limited to regional or single-center studies, hemodialysis patients who underwent frequent blood transfusions, or to at-risk populations (such as heroin addicts or HIV-positive patients) where the prevalence of TTI is expected to be higher.This retrospective cross-sectional study included all blood donations performed in Saudi Arabia during the year 2020. Demographic data and TTI-reactivity were retrieved and analyzed from the MOH annual statistics report. Based on national blood donation and screening protocols, eligible donors must be between 18-60 years of age with no history or current of TTI disease, weigh >50 kg, with a hemoglobin level of >12.5 g/dL, and with normal blood pressure. All donations were screened for HBsAg, anti-HBc, anti-HCV, anti-HIV-1 and -2, anti-HTLV I/II, syphilis, and malaria by chemiluminescence and NAT. Unscreened whole blood units are initially quarantined until all blood units are screened. Confirmed TTI-positive cases are automatically registered in the Health Electronic Surveillance Network (HESN) for further management and are banned from blood donation.This study was approved by the Ethical Committee of the MOH (21-71 E). All blood donors were requested to give informed consent prior to donation as per MOH regulations. The annual statistics report for the year 2020 was retrieved from the Blood Transfusion Services overseen by the MOH. Raw numbers of TTI reactivity were anonymously obtained without donors’ identification. For HBV and HCV serological screening, trademarks Architect i1000SR or Architect i2000 analyzers  operated by Abbott AxSym system with the ARCHITECT HBsAg Qualitative II Reagent kit, the ARCHITECT anti-HBs reagent kit, the ARCHITECT anti-HBc II Reagent kit, and the ARCHITECT anti-HCV Reagent were used. Readings >1.00 were labeled reactive.It was difficult to track all screening kits and equipment used over the study period; however, all were Food and Drugs Administration-approved as required by the MOH.For anti-HTLV-I/II screening the Abbott-Murex HTLV I/II enzyme immunoassay (EIA) , latex immunoassay , or chemiluminescent microparticle immunoassay (CMIA) Abbott ARCHITECT i2000SR were used. To confirm the initial screening results, positive samples were further tested by western blot . The Architect system HIV antigen/antibody combo CMIA was used for the detection of HIV p24 antigen and HIV-1/-2 antibodies. Human immunodeficiency virus Ab-Ag positive results were confirmed by INNO-LIA HIV I/II score. In addition, all donations were subject to NAT using CobasTaqScreenMPX Test, version 2.0  for the simultaneous detection of HBV-DNA and RNA of HCV and HIV.For syphilis screening, the CMIA Siemens immulite® 2000 XPi Immunoassay System was used to detect anti-Treponema pallidum (TP) antibodies, and the rapid RPR-carbon test and the Syphilis TP reagent Kit for the ARCHITECT i1000SR analyzer  were used to confirm positive findings. For malaria, a thick blood smear stained with Giemsa stain and EIA  tests were performed.Transfusion-transmissible infections frequency rate was estimated according to the formula:TTI incidence=(confirmed cases)/ x 100,000 independence test followed by post-hoc pairwise Fisher exact test due to low expected frequencies. The graph was illustrated in a mosaic plot using HSV shading with user-defined cutoffs (2 and 4) based on heuristics to display the absolute value of the residuals associated with each tile. Correspondence analysis was performed to explore the relationships between each geographical region and each TTI marker frequency by cross-tabulation with total variance of 98.8%. The contingency table was graphically illustrated as a biplot. Mosaic plot and biplot were generated by factoextra R package version 4.1.2. .The nationwide prevalence of confirmed TTI markers was expressed in percentages relative to total TTIs using GraphPad Prism 9.0 . Association between TTI markers and geographical regions was evaluated using χA total of 375,218 donations were registered nationwide, of which 32,785 (8.7%) were found to be reactive to TTI biomarkers by routine chemiluminescence or NAT screening assays. Subsequent confirmatory tests performed on reactive donors revealed a total of 8,466 confirmed cases . RepeateThe nationwide TTI prevalence is estimated to be 2,256 per 100,000 blood donors and the prevalence of TTI-positive donors per infectious agent is illustrated in  It is therefore not surprising for the central region to have the highest TTI prevalence among blood donors with 3,188 cases representing 4.2% of regional donations, as shown in The central region is the most populated region in Saudi Arabia and accounts for 15.1% of the national blood pool supply.Stratification of TTI prevalence against the 5 main geographical areas demonstrated that anti-HBc seropositivity was the dominant TTI biomarker in all but the central region, which instead had the highest HBV NAT prevalence . Anti-HBInterestingly, 76% of nationwide HBV NAT-positive donors were reported in Riyadh . Qassim Hepatitis C virus markers (anti-HCV and HCV NAT) were most prevalent in the central and Southern regions . Most anDiscarded blood units due to HIV, HTLV, syphilis, or malaria reactivity were predominantly reported in the central and Southern regions. The prevalence of anti-HIV was 0.041% in the central region and 0.027% in the Southern region . Prevale The WHO global status report on blood safety and availability, published in 2013, demonstrated that the median rate of global blood donor deferral was 12%, and that of Saudi Arabia was 6.5%. However, the reported rates did not clarify whether donor deferral was solely due to TTI reactivity or to absence of donor selection criteria.The prevalence of TTI-reactivity among blood donors in Saudi Arabia during 2020 is reported in this study. Blood donors with confirmed TTI reactivity represented 8.7% of nation-wide asymptomatic donors, mostly reported from the center (37%) and the South (33%), thus urging the need to investigate the reasons for the increased TTI reactivity in those regions. This rate of donor deferral due to TTI reactivity is lower than that of other Eastern Mediterranean countries. Anti-HBc represented 52.5% of all TTI-positive markers, followed by HBV NAT (22.8%) and HBsAg (10.4%). These distributions are in agreement with local regional studies. Anti-HBc is a valuable marker for HBV exposure irrespective of the current infectious state, especially at the end of a resolving infection when HBsAg and HBV NAT may not be positive. Hepatitis B surface antigen is indicative of active infection whereas HBV NAT is a marker of chronic infection. The relatively high frequencies of HBsAg and HBV NAT among blood donors is an interesting observation given that HBV vaccination has been mandatory in Saudi Arabia since 1989. In addition, the country follows stringent screening programs for all pilgrims and non-Saudi employees. In our study, donor ages and vaccination profiles were not included in the annual statistics report; thus, we were not able to stratify HBV seroprevalence based on age groups or explore whether a booster vaccine is recommended for isolated anti-HBc vaccinated subjects. It has been reported that even after HBV vaccination, the prevalence of anti-HBs (such as a marker of immunization that was not reported here) can progressively decrease with age in the presence or absence of anti-HBc.Donors with confirmed reactivity to HBV biomarkers comprised 85.6% of all confirmed TTI cases. This is not surprising given that Saudi Arabia has a low to moderate prevalence of HBV chronic disease (such as ≥2% of population). It was hypothesized that HBV prevalence in these regions might be influenced by populations of neighboring countries known to be HBV endemic. Three decades later, our study demonstrated a different HBV prevalence pattern with the Southern and central regions emerging as areas with the highest HBV prevalence.An earlier, population-based survey in Saudi Arabia identified the Southern region and Tabouk province as hyperendemic areas for HBV. Such a strategy was based on periodic epidemiological studies confirming the low endemic state of HBV in Germany. Hepatitis B surface antigen screening is considered of minimal value in reducing HBV-associated risk when performed in combination with HBV NAT and anti-HBc tests. Whether HBsAg screening is crucial for blood safety was not analyzed here. This is attributed to the nature of the retrieved data which provided the sum of TTI-reactive donors per province without detailing each donor’s serology and NAT profile. Given that Saudi Arabia is considered a high-income country and is a destination for working force from all around the world, the inclusion of HBsAg test in the screening protocol may be justified as an affordable precautious measure. Additionally, the possible transmission of occult HBV from NAT-negative donors and the low-moderate HBV endemicity similarly justify the inclusion of HBsAg in the routine screening panel.Every country must establish its own screening strategy based on its unique epidemiology and economy. For instance, in Germany, mandatory HBV screening includes HBsAg and anti-HBc, while HBV NAT is optional and only considered on a case-by-case basis. Likewise, the prevalence of other TTIs was considered very low and within the range of upper-middle income countries.The prevalence of HCV markers was relatively low among blood donors. This finding was expected provided that the Saudi Arbaia has a very low hepatitis C viremic prevalence (0%-0.6%).It is important to stress that the nature of our data merits cautious interpretation and limits the generalizability of our findings. A major limitation of this study was that the sum of TTI-reactive donors in each province was reported instead of detailed serology and NAT profile per donor. This did not allow for further investigation of disease epidemiology among blood donors or for assessment of variance between screening and confirmation.Our findings strongly support the health sector’s NTP initiative, which proposes establishing a centralized blood bank management model with interconnected systems. This is critical as the current fragmented system resulted in inconsistent data reporting, inability to determine blood bank shortage or overload, and which departments are associated with the most waste or inappropriate blood usage. Thus, a centralized management system with a database where blood donor information could be integrated would allow for continuous and accurate TTI surveillance and provide support to preventive plans and risk management for emerging viruses (such as Zika or Dengue viruses). The initiative would also improve financial management by setting up a single national inventory to accommodate supply and demand and to establish comprehensive metrics for quality performance.In conclusion, the current study demonstrates that reactivity to HBV dominated other TTI markers on a national level, with the central and Southern regions being hyperendemic for HBV. Until a detailed public epidemiology profile is available, the inclusion of HBsAg test in the current screening strategy seems to be a necessary precautious measure to ensure the highest standards of blood safety. However, a consensus is required to determine the clinical utility and financial feasibility of routinely testing for HBsAg. Such a consensus could be achieved through an integrated, nationwide network with a single inventory.We also recommend that future MOH statistical reports provide detailed donor demographics and essential variables  and report TTI pro-files per donor for more efficient data analysis.


Pancreatic cancer is one major digestive malignancy with a poor prognosis. Given the clinical importance of lncRNAs, developing a novel molecular panel with lncRNAs for pancreatic cancer has great potential. As a result, an 8-lncRNA-based robust prognostic signature was constructed using a random survival forest model after examing the expression profile and prognostic significance of lncRNAs in the PAAD cohort from TCGA. The efficacy and effectiveness of the lncRNA-based signature were thoroughly assessed. Patients with high- and low-risk defined by the signature underwent significantly distinct OS expectancy. Most crucially the training group’s AUCs of ROC approached 0.90 and the testing group similarly had the AUCs above 0.86. The lncRNA-based signature was shown to behave as a prognostic indicator of pancreatic cancer, either alone or simultaneously with other factors, after combined analysis with other clinical-pathological factors in Cox regression and nomogram. Additionally, using GSEA and CIBERSORT scoring methods, the immune landscape and variations in biological processes between high- and low-risk subgroups were investigated. Last but not least, drug databases were searched for prospective therapeutic molecules targeting high-risk patients. The most promising compound were Afatinib, LY-303511, and RO-90-7501 as a result. In conclusion, we developed a novel lncRNA based prognostic signature with high efficacy to stratify high-risk pancreatic cancer patients and screened prospective responsive drugs for targeting strategy. Pancreatic cancer is known as a highly lethal malignancy with a poor prognosis. Accounting for approximately 496,000 new patients per year worldwide, pancreatic cancer ranks 14th in new cases among 36 major types of cancer . HoweverNot surprisingly, considerable amounts of studies have revealed the possibility and value of molecular signatures in the diagnosis and prognosis of pancreatic cancer over the last few years. For instance, Wu et al. have developed a nine-gene  panel to predict the overall survival of pancreatic cancer . Other gTherefore, this study aims to identify the clinical significance of lncRNAs for pancreatic cancer evaluation and construct a comprehensive lncRNA-based signature with high prognostic efficacy to monitor outcomes of pancreatic cancer patients. Besides, the molecular signature is used to explore the immune landscape and potential therapeutic targets and small molecules between risk subgroups. In detail, expression and clinical data of pancreatic cancer patients were acquired from public databases including The Cancer Genome Atlas (TCGA), Cbioportal, and Cancer Cell Line Encyclopedia (CCLE). An 8-lncRNA classifier was then constructed by applying Cox and random survival forest (RSF) regression in differentially expressed lncRNAs (DElncRNAs). The capacity of the signature as a prognostic indicator was evaluated in different aspects. To emphasize, the immune feature landscape, possible therapeutic targets, and molecules were subsequently checked in patients with a high-risk score according to the signature in detail, holding the potential to expand the current therapeutic strategies for the pancreatic cancer population.http://portal.gdc.cacner.gov/repository) and the Cbioportal website . Fragments per million reads (FPKM) normalized expression value was used for further analysis. The cohort was then randomly split with a 2:1 ratio into a training group and a testing group.An RNA-seq dataset of 177 pancreatic cancer patients involving RNA expression value and matched clinical information was obtained from the TCGA data portal . To search for potential therapeutic agents, sensitivity data of compounds in CCLs were achieved from the Cancer Therapeutics Response Portal, Board institute  and PRISM repurposing dataset . The algorism of drug sensitivity was described in previous studies. Briefly, the database provided the area under the curve (AUC) values as the readout of drug sensitivity. The lower AUC values indicate higher drug sensitivity. Compounds with more than 20% missing data were excluded from the dataset, and the K-nearest neighbor algorithm (K-NN) was applied to estimate the AUC values. To further investigate the mechanism of actions (MoA) of the drugs screened out, the Connectivity Map tools database  with more than 2000 small molecule perturbagen types was applied for specific analysis.Expression profiles of human cancer cell lines (CCLs) were achieved from the Broad Institute CCLE project (http://gencodegenes.org/human). After the acquisition of lncRNA expression data as described above, the lncRNAs were separated from gene-coding RNA and other non-coding RNAs. Differentially expressed lncRNAs (DElncRNAs) were identified with the criteria of absolute log2 fold-change (log2FC) > 1 and adjusted p-value < 0.05 between tumor and control tissues. Afterward, univariate Cox regression was conducted to identify prognostic lncRNAs which shared a correlation with the overall survival (OS) time of the patients in the cohort (p < 0.05). Thus, the candidate prognostic lncRNAs were determined by overlapping the DElncRNAs and prognostic lncRNAs.The human lncRNA annotation profile was obtained from the GENCODE website  scoring method were employed to assess the response to immunotherapy, extent of immune dysfunction, immune exclusion, and microsatellite instability (MSI) for patients in high-risk and low-risk groups.p < 0.05 was considered significant.All statistical analyses were conducted with the R software platform . Some major R packages included “edgeR,” “limma,” “survival,” “ROCR,” “ggplot2,” “pRRophetic,” and “randomForestSRC”. To compare variables in multiple groups, Student’s t-test and ANOVA analysis were used for parametric factors, whereas the Wilcoxon rank-sum test and Kruskal–Wallis test were applied for nonparametric factors. To measure the correlation of different variables, Spearman’s rank-order correlation and Pearson’s r correlation were set. Furthermore, Kaplan-Meier and the log-rank test were used for survival analysis. The area under the curve (AUC) was measured to judge the efficacy of the receiver operating characteristic curve. For all statistical calculations, a two-tailed n = 177) and adjacent control (n = 4) was obtained from the TCGA portal as described above. Of the 14,078 lncRNAs extracted from the RNA-seq dataset, 540 lncRNAs were identified as DElncRNA under the condition of absolute log2 FC > 1 and adjust p < 0.05 (p < 0.05) that possibly correlated to the OS time of the patients. A Venn diagram was created by overlapping DElncRNAs and univariate COX positive lncRNAs to select the candidate lncRNAs  analysis was subsequently performed. The areas under the ROC curve (AUCs) of the classifier were 0.94, 0.97 and 0.90 for 1, 3, and 5 years of anticipation in the training group , these DEGs were significantly enriched in 27 pathways in the high-risk group and 16 pathways in the low-risk group, respectively. Among them, cell cycle, DNA replication, retinol metabolism, spliceosome, and systemic lupus erythematosus were the top 5 KEGG pathways enriched in the high-risk group according to normalized enrichment score (NES), while calcium signaling pathway, hematopoietic cell lineage, neuroactive ligand-receptor interaction primary immunodeficiency and renin-angiotensin system were the most relevant pathways in low-risk group  was applied to investigate distinguished genes, pathways, and biological processes between subgroups with a different risk scores. In specific, 1755 differentially expressed genes (DEGs) were identified between the high-risk and low-risk subgroups at the condition of absolute log2FC > 1 and sk group . In addisk group .http://software.broadinstitute.org/gsea/misigdb) were also checked. Interestingly, gene clusters related to E2F targets, G2M checkpoint, glycolysis, interferon α response, and MYC targets were the top hallmarks positively correlated to the high-risk group, but only 3 clusters, allograft rejection, KRAS signaling, and pancreas β cells were relevant to the low-risk group in our whole cohort  and compared between risk subgroups  from CTRP and 5 compounds  from PRISM were identified in which all these molecules had a significantly lower value of AUC in high-risk patients compared to low-risk ones  and low-risk (bottom 20%) patients to screen out agents with lower estimated AUC values in high-risk patients (log2FC > 0.05). Subsequently, spearman correlation analysis was applied between the AUC value of specific candidates and the risk score of the patients, in which correlation coefficient isk ones .via CTRP and PRISM were evaluated in the CMap library, respectively. And all agents with CMap score less than −95 were also listed below  database including nearly 3000 small-molecule compounds was applied. The CMap algorithm compares the expression profile of DElncRNAs in different risk subgroups with the existing response pattern of gene expression for thousands of drugs and molecules in the library. In specific, the CMap score of less than −95 will be considered potentially effective. Positive agents selected ed below .As a lethal malignancy that causes the second most cancer-related death, pancreatic cancer remains a critical global health challenge. Despite tremendous progress has been made during past decades in understanding the genesis and development of this fatal disease, only a fraction of patients have the opportunity to receive radical or surgical resection. Currently, an increasing number of curative approaches including chemotherapy, targeted therapy, or immunotherapy are available for patients with unresectable or metastatic disease, but with merely reluctant effects. To improve the process of clinical decision-making, physicians and surgeons dedicated years to looking for novel strategies for better diagnosing and prognosis guiding for pancreatic cancer. At the moment, clinicians depend largely on pathological factors such as TNM classification, AJCC tumor staging, or histological grade of the tumor to select proper therapy and forecast the outcome for a certain patient. Nonetheless, novel biomarker panels with high accuracy and specificity are widely accepted as a promising approach that could shed light on improving clinical surveillance and management of pancreatic cancer.via binding to miRNA-1231 and competing for the endogenous RNA (ceRNA) mechanism , circular RNA (circRNA) and lncRNA have been increasingly emphasized in tumor biology. Numerous studies have revealed that dysregulated lncRNA participates in processes of carcinogenesis and progression of pancreatic cancer. For instance, Liu has reported that lncRNA NR2F1-AS1 promotes proliferation and invasion of pancreatic cancer by regulating the neighboring NR2F1 gene and activating AKT/mTOR signaling pathway . Huang hechanism . As our The major pursuit of the present study is to construct a lncRNA-based molecular signature that hosts high efficacy in predicting the outcomes of pancreatic cancer. We have noticed that all patients with pancreatic cancer are now treated with one universal norm mainly based on imaging experiments. The lack of corresponding biomarkers and specified measures possibly result in unsatisfactory therapeutic effects. Therefore, another purpose of the study is to develop a tailored treatment for a certain proportion of patients with possible high risk and worse outcomes.via Kaplan-Meier survival analysis. The result indicates a huge gap between the subgroups where individual samples with high-risk scores reveal remarkably worse prognoses than their counterpart in low-risk groups. In addition, the signature exhibits superior efficacy in prognosis anticipation, where the AUC value in ROC analysis exceeds over 0.90 for all 1, 3, and 5 years prediction of OS in the training group and reaches 0.75 to 0.83 overall. Furthermore, the signature was approved by the uni- and multivariate Cox as one independent predictive factor with marked significance. Last but not least, a combined prediction model that includes multiple associated factors was carried out using a nomogram to put the prognosis prediction of pancreatic cancer into practice.To achieve these goals, the TCGA-PAAD cohort was randomly split and applied for prognostic analysis. After screening out the differentially expressed lncRNAs and prognostic lncRNAs that were Cox-positive, an RSF model based on minimal depth were established to finally identify target lncRNAs and to form a lncRNA based classifier with the highest efficacy and effectiveness. Hence, the cohorts were subsequentially divided into high-risk and low-risk groups according to the median value of the risk scores by the signature. The survival status of the high-risk and low-risk groups was then compared via manipulating the methylation of miRNA-34a  has been widely accepted as one symbolic event in early and advanced tumorigenesis. Also, several studies confirmed increased M2 deviation of macrophages that promotes tumor behaviors including tumor proliferation, metastasis, and immune escape in pancreatic cancer . MoreoveBesides, the gene enrichment and tumor immune analysis unanimously observed an increased interferon-alpha response in the high-risk subgroup. As one of the oldest immune-based therapeutic options for cancer treatment, interferon-alpha is widely used to suppress tumor growth in melanoma, lymphoma, renal carcinoma and so forth. In pancreatic cancer, some clinical trials suggested that chemotherapy based on interferon might improve the overall outcome after surgical resection . NonetheIn addition, the potential responsibility for the immunotherapy was evaluated by TIDE analysis. Paradoxically, the result indicated that the high-risk group positively correlated with the declined level of TIDE score and immune dysfunction to their low-risk peer, suggesting promising anticipation of therapeutic effect in the high-risk group. To our knowledge, the TIDE algorithm was built on specific tumor types of melanoma and non-small cell lung cancer (NSCLC). The unique characteristic of heterogeneity and immunosuppression in pancreatic cancer could leave the result debatable. In sum, further studies are drastically needed to gain a deeper understanding of immune activity in pancreatic cancer before novel promising therapeutic strategies are to be developed.via CTRP, PRISM and CMap databases. As the only agent identified by CTRP and PRISM with a negative CMap score, Afatinib belongs to the tyrosine kinase inhibitor family and is mainly effective for epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2). Afatinib, under the commercial name of Gilotrif, has received approval as a first-line treatment for NSCLC. Other indication includes advanced breast cancer with HER2 positive. On-going and complete clinical trials are revealing the potential efficacy of Afatinib in lung cancer other than NSCLC, Head, and Neck squamous cell carcinoma, glioma, and prostate cancer . LY303511 inhibits the activity of casein kinase 2, which is known to prompt the translation from the G1 to G2 phase and therefore down-regulated cellular proliferation in A549 cells . AfterwaLa cells . Howevero models . Runningo models .To. conclude, this study generated a novel lncRNA-based signature based on a random forest model to predict the overall survival of pancreatic cancer. The efficacy and effectiveness of the signature were evaluated individually and combined with other clinical characteristics. This lncRNA panel, either alone or in combined efforts with other clinical factors, can provide a novel strategy for prognosis anticipation and clinical decision of pancreatic cancer. High-risk patients entitled to the signature tend to have considerably worse outcomes than their low-risk counterparts. And enhanced immunosuppression might be one reasonable explanation. Last but not least, potential therapeutic molecules were excavated from public databases. The result turns out Afatinib, LY-303511, TG-101348 and Pirarubicin could be candidates that are particularly effective for patients with a high-risk score. But before understanding all this, more efforts on validation and mechanistic exploration of these genes and drugs are still in great demand.


Cutaneous squamous cell carcinoma (cSCC) is an increasingly prevalent and morbid cancer worldwide. Management of this cancer has changed significantly in the last decade through improved risk stratification and new therapies offering patients with locally advanced and metastatic disease more effective, less toxic, and more durable treatment options. Ongoing clinical trials are assessing new therapeutic options as well as optimizing existing regimens in efforts to better manage this cancer. The recent developments highlight the need for multidisciplinary care, especially for those with locally advanced and metastatic disease.cSCC is increasing in prevalence due to increased lifespans and improvements in survival for conditions that increase the risk of cSCC. The absolute mortality of cSCC exceeds melanoma in the United States and approaches that of melanoma worldwide. This review presents significant changes in the management of cSCC, focusing on improvements in risk stratification, new treatment options, optimization of existing treatments, and prevention strategies. One major breakthrough in cSCC treatment is the advent of immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1), which have ushered in a renaissance in the treatment of patients with locally advanced and metastatic disease. These agents have offered patients with advanced disease decreased therapeutic toxicity compared to traditional chemotherapy agents, a more durable response after discontinuation, and improved survival. cSCC is an active field of research, and this review will highlight some of the novel and more developed clinical trials that are likely to impact cSCC management in the near future. The risk of metastatic disease in a patient with cSCC is approximately 2–4%, most commonly to the regional lymph nodes; however, the overall risk depends on the tumor subtype, location, and patient comorbidities ,2. It waShifts in patient demographics are influencing the incidence and development of cSCC. Patients with a history of drug-induced immunosuppression, HIV, lymphoma, leukemia, certain genetic syndromes , and solid organ transplant recipients (SOTR) are at higher risk of developing cSCC with a more aggressive clinical course ,7,8,9,10Identifying trends in cSCC epidemiology is challenging due to a multifactorial etiology coupled with inconsistent registry tracking—currently the CDC’s National Cancer Registry does not track cSCC. The annual incidence of cSCC is estimated to be 1.8 million cases . For comUnlike BCC, cSCC typically portends a worse prognosis. It is estimated that over 15,000 people die of cSCC in the United States annually . Despiten = 231) of cSCC diagnosed at a single institution were considered high-risk based on then-current guidelines, suggesting the guidelines are highly sensitive [The 2022 National Comprehensive Cancer Network (NCCN) guidelines define high-risk and very high-risk cSCC based on the presence of risk factors for local recurrence, metastasis, or death . In contensitive . While tDespite the overall low risk of metastasis, cSCC is the second most common cancer worldwide, and the absolute number of patients with metastatic cSCC is increasing. Metastatic cSCC is associated with decreased survival compared to local disease, leading to attempts to stratify patients based on risk for metastasis ,2,27. ThSeveral staging systems have been proposed to predict risk of metastasis in cSCC . The 7thSchmitt et al. conducted a meta-analysis comparing the performance of AJCC7 to BWH in predicting sentinel lymph node biopsy (SLNB) positivity . The ratRuiz et al. compared AJCC8 performance with BWH when applied to a large cohort at a single center institution, focusing on metastases and deaths . The higGiven the predilection of cSCC for regional lymph nodes, SLNB is well suited to detect occult metastatic disease. The overall rate of SLNB positivity is 13.9% and false negativity is 4.6% . PatientA recently developed prognostic 40-gene expression profile test performed on biopsied cSCC tissue allows patients to be stratified into three groups based on three-year metastasis risk . A retroExpression of individual tumor markers is prognostic in cSCC. Tumor expression of programmed death-1 ligand (PD-L1) carries increased risk of nodal metastasis according to a meta-analysis of seven studies (odds ratio 2.34) . AdditioStaging imaging studies are not indicated for all cases of cSCC due to the low overall risk for metastasis. Imaging is most commonly employed to screen for subclinical regional metastasis. Although limited data are available regarding imaging of cSCC, it is recommended that imaging of the regional lymph node basin be considered for BWH stage T2b and T3 cSCCs ,49,50.In the United States, nodal basins are typically evaluated by computed tomography (CT) with contrast due to the relatively low cost, high speed, ability to assess cortical bone involvement, and spatial information provided . UltrasoImaging may be considered for locally advanced disease or pre-operative planning purposes . FurtherSurgical excision is the gold standard treatment for cSCC, but topical therapies are often employed for lower risk cSCCis and may be utilized as an adjunct in non-surgical candidates or those who refuse surgery. The most frequently used agents are 5-fluorouracil (5-FU), imiquimod, and destructive acid . There are limited quality data regarding efficacy, but Bennardo et al. conducted a systematic review encompassing 49 patients treated with 5% 5-FU, 3.75–5% imiquimod, 0.1% tazarotene, and/or 80% trichloroacetic acid . The resIn the author’s experience, adjunctive topical therapy with either 5-FU or imiquimod is a valuable tool to decrease surgical mobidity and disfigurement, particularly for Mohs cases, in which there is residual cSCCis on a peripheral margin after clearing the invasive tumor, or when operating in a patient with field cancerization. Topical therapies are well-suited for human papillomavirus (HPV)-associated cSCCis that are multifocal  and have been reported as an adjunct when surgical margins are positive in HPV-associated cSCC .Destruction with liquid nitrogen or curettage and electrodesiccation (C&E) are treatment options for low-risk cSCC. A pooled analysis of eight retrospective observational studies revealed a recurrence rate of 1.7% and 0.8% for C&E and cryotherapy, respectively . HoweverSurgical excision is effective for most cSCCs. Both NCCN and AAD recommend 4- to 6-mm clinical margins for standard excision of low-risk cSCC, with the AAD specifically recommending excision to the depth of the subcutaneous adipose tissue ,40.Mohs micrographic surgery (MMS) results in superior histopathologic verification of complete tumor extirpation and allows for maximum conservation of tissue compared to standard surgical excision . This teRT is an option for primary treatment of cSCC when surgery is contraindicated, associated with high morbidity, or not preferred by the patient. Because of potential long-term sequelae, patients over the age of 60 years old are preferred candidates. High-level evidence of this treatment modality is lacking; current data are limited by small patient numbers, variable follow-up durations, and heterogeneity of RT modality employed. Cure rates of RT have been shown to be lower than standard surgical excision . SmallerPhotodynamic therapy (PDT) is widely used for field treatment actinic keratoses and involves topical application of a photosensitizer, such as aminolevulinic acid or methyl aminolevulinate. Due to reports of high recurrence with PDT, as well as a lack of high-level evidence for its use, PDT is generally not recommended for cSCC ,62,63. P2 demonstrated a 6.8% recurrence rate at 18 months mean follow-up [Limited data exist for laser treatment of cSCC in the literature . No studollow-up .Laser-assisted drug delivery augments the distribution and penetration of topically applied treatments by utilizing ablative fractional laser (AFL). Two randomized controlled trials showed clearance of cSCCis with AFL-PDT was 87.0–87.5% versus 50.0–55.3% for the PDT-only arm at 12 months ,67. A caLocally advanced or metastatic cSCCs not amenable to surgical excision or radiation therapy require a more aggressive therapeutic approach . Prior tTreatment-related toxicities are a significant concern for patients undergoing cytotoxic chemotherapy . More thIntralesional interferon represented the first use of immunotherapy for the treatment of cSCC in 1992 ,78. SincRepeated skin exposure to mutagens such as ultraviolet radiation is a major pathogenic factor in the development of cSCC . Tumor cPD-1 is a transmembrane receptor expressed on T-cells, B-cells, and natural killer cells and serves as an immune regulating checkpoint. PD-L1, its ligand, is expressed on tumor and antigen-presenting cells . The binCemiplimab is a human monoclonal immunoglobulin G4 antibody directed against PD-1 . In 2018A 43-month follow-up analysis of the phase II study  is an immune checkpoint receptor expressed on T-cells. The binding of CTLA-4 to B7, its costimulatory protein receptor on antigen presenting cells, decreases T-cell regulatory activation ,95. BlocIpilimumab is a human monoclonal antibody against CTLA-4 and is FDA-approved for treatment of unresectable or metastatic melanoma . While gThe epidermal growth factor receptor (EGFR) is a tyrosine kinases receptor involved in signaling pathways critical for cell proliferation, migration, differentiation, regulation, and survival . Tumor dData supporting the efficacy of EGFR inhibitors in the treatment of cSCC are limited to a few prospective studies that are summarized in Side effects of EGFR inhibitors are typically less severe than those seen with cytotoxic chemotherapy. The most common adverse event is an acneiform eruption, reported in 50–100% of patients and a major cause of drug cessation or poor treatment adherence . InterescSCC is most commonly limited to the skin, allowing direct access of therapeutics to the tumor site. While systemic agents can elicit a variety of adverse events, intratumoral injection increases local drug concentrations and potentially diminishes systemic toxicities . IntraleMethotrexate (MTX) is an anti-metabolite therapy commonly used for its anti-tumoral and immunosuppressive effect against tumors and autoimmune disease . As a co2 versus 7.72 cm2 in the non-responder group, and all tumors were treated with the same protocol, two 20 mg treatments spaced 1 week apart, regardless of the tumor size [Intralesional methotrexate has had some success in the treatment of localized cutaneous squamous cell carcinoma without metastasis. In a single-center, prospective study that included 65 cases of cSCC treated with intralesional MTX prior to surgical treatment, 92.3% of patients showed a clinical response, with 58.5% of patients having no residual dysplasia on the subsequent excision pathology . The meamor size . Annest mor size . On avermor size . MTX is mor size . MTX toxmor size .5-FU is fluoropyrimidine that is converted to its active metabolite in the cell and disrupts RNA synthesis . IntraleWhile surgical excision of cSCC is often the standard of care, combining therapeutic modalities has been common practice since for high-risk cSCC. Systemic therapy can be coupled with surgery or RT as adjuvant or neoadjuvant therapy .Adjuvant RT reduces the likelihood of recurrence and metastasis after surgical excision . HoweverAdjuvant chemotherapy includes the use of various antitumor agents including platinum-based agents  as well as anti-metabolites . Similar to adjuvant RT, studies on adjuvant chemotherapy are predominantly retrospective in nature with small patient cohorts . Due to For locally advanced cSCC, consideration of immunotherapy and/or RT is recommended when surgery is unable to clear the tumor or would result in significant disfigurement or loss of function . NumerouOral retinoids have been shown to reduce the incidence of cSCC in patients with certain high-risk factors—SOTR, genetic predisposition , and prior PUVA exposure; however, the retinoids do not produce a durable response and benefits quickly abate after cessation of therapy ,128,129.The benefits of chemoprevention are less distinct for other therapies and patient groups at high risk. Weinstock et al. demonstrated a 75% reduced risk of developing cSCC at 12 month follow-up with the prophylactic use of 5-FU cream compared to placebo in patients with a history of NMSC . Study pNicotinamide, a variant of vitamin B-3, has shown efficacy in the chemoprevention of actinic keratoses and NMSC in those at elevated risk. In a phase 3 double-blinded randomized controlled trial, nicotinamide 500 mg BID resulted in a 30% reduction in cSCC after 12 months of therapy . SmallerCapecitabine is an oral precursor to 5-FU, an agent commonly used as a topical treatment of NMSC and actinic keratoses. Lewis et al. first reported capecitabine-associated inflammation of actinic keratoses in a patient treated for metastatic colorectal carcinoma . This anDespite early evidence that NSAIDs may decrease the risk of cSCC, a subsequent meta-analysis showed no chemopreventive benefit . Both thPDT is widely used for field treatment of actinic keratoses and has been used off-label for multiple indications, including the treatment of low-risk NMSC, as discussed earlier. Data on the use of PDT for prevention of NMSC are limited. One study of 12 SOTR patients found a 79% and 95% reduction in the number of cSCC at 12 and 24 months, respectively, when treated with cyclic PDT every 4–8 weeks . AdverseAs of May 2022, there are 179 clinical trials for cSCC. The biggest trend with the current trials is the use of ICIs, including three novel agents targeting PD-1 and/or PD-L1 ,143,144.Investigational drugs targeting CD-47, CD-40, TGFβ1, COX-2, and the STING pathway are being studied as monotherapy for cSCC ,155,156.Oncolytic viruses, viruses that have been genetically modified or selected for anti-tumoral activity, have been used previously in melanoma and other solid tumors. Talimogene laherparepvec (T-VEC) is a genetically modified herpes virus used in the treatment of stage III and IV melanoma and was the first to be FDA approved in the US. T-VEC is currently being studied in small trials for the treatment of cSCC as monotherapy or in combination with panitumumab or nivolumab ,164,165.Treatment of locally advanced and metastatic cSCC in SOTR patients poses significant challenges. First-line treatments, including RT with chemotherapy or EGFR inhibitors, are limited by their modest efficacy and low tolerability. ICI treatment is limited by the risk of grafted organ rejection, which approaches 42% in renal transplants . NCT0433Given the variable and dynamic response of ICI therapy, several trials are assessing factors that may better predict response to therapy. Based on data from murine studies and patients with melanoma, two trials are evaluating fecal microbiota, including one that involves fecal transplant from ICI responders to ICI non-responders ,172. TwoTraditional surgical and destructive methods remain the standard of care for low-risk cSCC; however, management of high-risk, locally advanced, and metastatic cSCC has evolved significantly in the last decade to include more efficacious, durable, and tolerable therapeutic options. With the increasing incidence of cSCC and growing number of patients with high risk factors, it is imperative that clinicians continue to expand their treatment armamentarium to include the most recent advances.


Safe provision of systemic anti-cancer treatment (SACT) during the COVID-19 pandemic remains an ongoing concern amongst clinicians.Retrospective analysis on uro-oncology patients who continued or started SACT between 1st March and 31st May 2020 during the pandemic (with 2019 as a comparator).p < 0.0001) and 94.44% fewer patients receiving radical treatment (p = 0.00194). The number of patients started on a new line of SACT was similar between both years  but with 53.45% fewer patients started on chemotherapy in 2020 (p < 0.001). Overall, 5 patients tested positive for COVID-19 . Compared to 2019, 30-day mortality was similar  whereas 6-month mortality was lower  in 2020.441 patients received SACT in 2020  compared to 518 patients in 2019 . In 2020, there were 75.00% fewer patients with stage 3 cancers receiving SACT (This study suggests that delivery of SACT to uro-oncology patients during COVID-19 pandemic may be safe in high-incidence areas with appropriate risk-reduction strategies.The online version contains supplementary material available at 10.1186/s12894-022-01023-6. On the 23rd of March 2020, the UK government officially announced the first national lockdown in response to the COVID-19 pandemic. Over the past two years, we have seen dramatic changes in healthcare service provision, repurposing of drugs for severe COVID-19 infections, and the arrival of COVID-19 vaccines. Coming out of the third wave with anticipation of emerging new variants of COVID-19, we need to address ongoing concerns on how to deliver essential non-COVID-19 services to the public.All aspects of cancer services have been significantly impacted by the pandemic, resulting in a backlog of patients who may present with more aggressive disease or in extremis. During the early stages of the pandemic, initial observational studies suggested that having active cancer and receiving systemic anti-cancer treatments (SACT) increased a patient’s risk of severe COVID-19 and subsequent death . Since tWhilst the national institute for health and care excellence (NICE) and international experts have provided recommendations on the prioritisation of cancer treatments, the ability to deliver these will vary depending on resources available to the healthcare provider. There have been several published articles providing practical recommendations on the management of patients with cancer during the COVID-19 pandemic , 14. OurDuring the first wave of COVID-19 there were several key changes in how we restructured our cancer services in order to provide essential cancer services whilst minimising the risk of COVID-19  [All patients at a tertiary cancer centre in London receiving at least one SACT cycle for a urological cancer between 1st March 2020 and 31st May 2020 were included for data analysis. We used the same timeframe in 2019 as a comparator group. Patient demographics, oncological characteristics, SACT information, and COVID-19 status were extracted using our patient electronic records and chemotherapy prescribing system. Socioeconomic status was categorised into low, middle, and high using the English Indices of Multiple Deprivation (IMD) ranking based on postcodes. Cancers were staged according to the UICC 8th staging system. COVID-19 infection was defined as a positive RT-PCR test. Patients with only radiological changes or symptoms suggestive of COVID-19 without a positive RT-PCR test were excluded. COVID-19 positive patients were then categorised into asymptomatic, mild, moderate, or severe disease as defined by the WHO criteria . Chi-squNW/0297) .p < 0.0001) which made it difficult to comment on any differences.In the study period, there was a total of 441 patients who received SACT in 2020  compared to 518 patients in 2019  with an overall decline of 14.86% (Table p < 0.0001) compared to stage 4 cancers  in 2020. This difference was best observed with prostate cancer where there were 18 fewer patients with stage 3 cancers who received SACT in 2020  . There was a greater decline in the proportion of patients who received SACT with stage 3 cancers  and targeted therapy . This was particularly evident in renal cancers with a decline of 42.71% in the number of patients receiving targeted therapy (p < 0.0001) , there was no significant difference in the number of patients receiving hormone therapy  and fewer patients going onto 3rd line palliative SACT  (Table p = 0.790).Hormone treatment was the most common type of SACT delivered followed by chemotherapy, targeted therapy, and immunotherapy in both 2019 and 2020. The largest reductions were seen with chemotherapy . However, further subgroup analysis suggests that there were less patients with prostate cancer being started on SACT  and less patients with urological cancers started on chemotherapy  in 2020 (Table p = 0.649) compared with 2019 (Table p = 0.0209).The number of patients that were started on a new line of SACT was similar between both years  . The low rates of COVID-19 infections in our patients during the first wave would have also been impacted by national lockdown procedures and high levels of shielding due to our clinically vulnerable groups. Of the urological cancers, patients with prostate and renal cancers were most affected with reductions in delivery of both chemotherapy and targeted therapy respectively. This reflects clinical decision making whereby on a case-by-case basis treatment was either deferred or commenced without delay based on symptoms, growth rate of cancer, and patient factors. For instance, patients with slow growing metastatic renal cancers might have been advised to delay starting SACT for a short number of months in order to avoid hospital visits, risk of infection, and toxicities. Whereas patients diagnosed with advanced urothelial carcinoma were generally recommended to start SACT since a delay would likely lead to progressive disease over a short time period. Although there was a small increase in the number of patients receiving combination targeted/immunotherapy, this reflects the availability of axitinib/avelumab for untreated advanced renal cancers rather than an effect of the pandemic . ReassurThese differences reflect initial concerns regarding chemotherapy as a potential risk factor for severe COVID-19 . HoweverThe decline in 6-month all-cause mortality during COVID-19 was another interesting finding. However, this figure does not take into account the proportion of patients who died from cancer and did not receive SACT due to the potential risk of contracting COVID-19 outweighing any survival benefits. There may also be an element of selection bias as the patients who were receiving SACT during COVID-19 were generally younger and of good performance status. There may also be a general decline in deaths from other nosocomial and community infectious diseases due to shielding, social distancing, and increased vigilance in infection control protocols –25.It is important to appreciate the certain limitations to our study. The main limitation was that we only included patients who received SACT during COVID-19 and did not include all patients who were potentially eligible for SACT but were not given it either due to patient decision or as a result of treatment prioritisation with risk of COVID-19 infection. Therefore, we cannot comment on mortality outcomes due to this. We also only included patients with a positive COVID-19 RT-PCR test. This would have likely missed patients who were self-isolating with mild symptoms who did not get tested, death certificate diagnosis of COVID-19 in patients presenting in extremis without time for an RT-PCR test, and false negative RT-PCR results. Another limitation is the proportion of patients with incomplete data on ethnicity and performance status in the patient electronic records. This is particularly relevant as there is growing evidence that there are significant racial and socioeconomic disparities in healthcare access during COVID-19. The method of data extraction from our electronic chemotherapy prescribing system also underrepresents the number of patients with prostate cancer receiving anti-gonadotropic monotherapy  as the prescriptions are continued by GPs. Finally, we do not have data regarding the provision of SACT during the second wave of COVID-19. This would be an important aspect for us to study as there were more variables to consider including availability of COVID-19 treatments, emerging safety evidence of SACT, expert consensus statements, and the arrival of novel vaccines.This single-centre retrospective study demonstrated that patients could receive a range of SACT during COVID-19 with a low incidence of infection rate and mortality. Although shifts in the type of SACT delivered were observed with less chemotherapy administered, we were able to continue to start patients on SACT. With emerging new variants and easing of national lockdown measures, we hope that our data provides reassurance that SACT can be safely delivered during a pandemic with appropriate safety provisions in place. Furthermore, current strategies should also include stringent vaccination programs for patients with cancer considering the availability of COVID-19 vaccines and emerging data on its reduced efficacy in this population .Additional file 1: Table S1. Patient demographics of prostate, renal, urothelial, and testicular cancer groups. Table S2. Oncological characteristics of prostate, renal, urothelial, and testicular cancer groups.