Weathering the COVID-19 storm: Lessons from hematologic cytokine syndromes.

A subset of patients with severe COVID-19 develop profound inflammation and multi-organ dysfunction consistent with a "Cytokine Storm Syndrome" (CSS). In this review we compare the clinical features, diagnosis, and pathogenesis of COVID-CSS with other hematological CSS, namely secondary hemophagocytic lymphohistiocytosis (sHLH), idiopathic multicentric Castleman disease (iMCD), and CAR-T cell therapy associated Cytokine Release Syndrome (CRS). Novel therapeutics targeting cytokines or inhibiting cell signaling pathways have now become the mainstay of treatment in these CSS. We review the evidence for cytokine blockade and attenuation in these known CSS as well as the emerging literature and clinical trials pertaining to COVID-CSS. Established markers of inflammation as well as cytokine levels are compared and contrasted between these four entities in order to establish a foundation for future diagnostic criteria of COVID-CSS.

A Meta-Analysis of Case Fatality Rates of Recurrent Venous Thromboembolism and Major Bleeding in Patients with Cancer.

BACKGROUND: Knowing the case fatality rates of recurrent venous thromboembolism (VTE) and major bleeding is important for weighing the relative risks and benefits of anticoagulation and deciding on the duration of anticoagulant therapy, but these rates are uncertain in patients with cancer-associated thrombosis. METHODS: We performed a systematic review and a meta-analysis to determine the incidence of recurrent VTE and major bleeding and their respective case fatality rates in patients with cancer-associated VTE. RESULTS: Our analysis included 29 studies (15 prospective cohort studies and 14 randomized controlled trials) from 1980 to January 2019. Data from 8,000 cancer patients with 4,786 patient-years of follow-up were summarized. Rates of recurrent VTE and fatal recurrent VTE were 23.7 (95% confidence interval [CI]: 20.1-27.8) and 1.9 (95% CI: 0.8-4.0) per 100 patient-years of follow-up, respectively, with a case fatality rate of 14.8% (95% CI: 6.6-30.1%). The rates of major bleeding and fatal major bleeding events were 13.1 (95% CI: 10.3-16.7) and 0.8 (95% CI: 0.3-2.1) per 100 patient-years of follow-up, respectively, with a case fatality rate of 8.9% (95% CI: 3.5-21.1%). While the estimates of case fatality vary by anticoagulation regimen and study design, the differences between them were not statistically significant. CONCLUSION: In cancer patients receiving anticoagulation, the case fatality rate of recurrent VTE is higher than the case fatality rate of major bleeding. These findings may help to inform decisions regarding the management of anticoagulation in patients with active cancer and VTE.

Case report: ischemic priapism secondary to tinzaparin.

Low-molecular-weight heparin (LMWH) therapy has recently been proposed as a cause of ischemic priapism. The evidence, however, remains scarce, as there are very few published cases of LMWH-induced priapism to date. The implications of such events are significant as ischemic priapism is a medical emergency. In current clinical practice we are seeing a trend towards LMWH therapies replacing unfractionated heparin (UFH). As LMWH therapies continue to gain favor, we will potentially see more cases of LMWH-induced priapism. As such, consideration should be given to determine the underlying pathophysiology and incidence of LMWH-induced priapism. Herein, we present the case of a 33-year-old male with priapism in the setting of tinzaparin treatment.

Upper gastrointestinal bleeding following transcatheter aortic valve replacement: A retrospective analysis.

OBJECTIVES: The aim of this study was to identify the incidence of upper gastrointestinal bleeding (UGIB) in the postprocedural period following transcatheter aortic valve replacement (TAVR). BACKGROUND: As TAVR moves into intermediate- and low-risk patients, it has become increasingly important to understand its extracardiac complications. The patient population undergoing TAVR have clinical and demographic characteristics that place them at significant risk of UGIB. Practical aspects of TAVR, including use of antithrombotic therapy, further increase risk of UGIB. METHODS: A retrospective single-center evaluation of 841 patients who underwent TAVR between January 2005 and August 2014 was performed in conjunction with analysis of referral patterns to the gastroenterology service for UGIB at the same site. RESULTS: The overall risk of UGIB following TAVR was found to be 2.0% (n = 17/841). Additionally, the risk of UGIB in patients receiving triple antithrombotic therapy was found to be 10-fold greater than patients not receiving triple antithrombotic therapy (11.8% vs 1.0%). Endoscopy findings demonstrated five high-risk esophageal lesions including erosive esophageal ulcers, visible vessels at the GE junction, erosions at distal esophagus, and an actively bleeding esophageal ring that had been intubated through by the transesophageal echocardiography (TEE) probe. CONCLUSIONS: This large cohort study demonstrates that TAVR is associated with a moderate risk of severe UGIB. The results of this study suggest that patients on triple antithrombotic therapy are at highest risk for severe UGIB. © 2016 Wiley Periodicals, Inc.

A novel endoscopic treatment for renal arteriopelvic fistula post-percutaneous nephrolithotomy (PCNL).

MAIN FINDINGS: We describe the use of a novel endoscopic approach in the management of unremitting gross hematuria following post-percutaneous nephrolithotomy (PCNL) in a 65-years-old male. This approach proved successful and cost-effective in managing haemorrhage post-PCNL when renal angiography failed to localize the source of bleeding. Case hypothesis: The recommended treatment modality for renal calculi ≥ 2cm is PCNL. It is essential that clinicians are aware of the various complications that can arise from PCNL, including arteriovenous fistula, which is typically managed with renal angio--embolization. The development of a renal arteriopelvic fistula (APF) is an extremely rare complication, and accounts of haemorrhage from renal APF and its treatment have not been well-described in the literature. We successfully hypothesized that the ureteroscopic localization, fulguration, and closure with a fibrin sealant at the site of the arterial bleed results in optimal treatment for this clinical presentation. We report this case in detail. Promising Future Implications: The successful and cost-effective endoscopic approach described here for treatment of post-PCNL renal APF and unremitting gross hematuria ought to be considered as an adjunct to renal angiography and embolization when the source of bleeding cannot be accurately identified using traditional imaging modalities.

A novel endoscopic treatment for renal arteriopelvic fistula post-percutaneous nephrolithotomy (PCNL)

Main findings We describe the use of a novel endoscopic approach in the management of unremitting gross hematuria following post-percutaneous nephrolithotomy (PCNL) in a 65-years-old male. This approach proved successful and cost-effective in managing haemorrhage post-PCNL when renal angiography failed to localize the source of bleeding. Case hypothesis The recommended treatment modality for renal calculi ≥ 2cm is PCNL. It is essential that clinicians are aware of the various complications that can arise from PCNL, including arteriovenous fistula, which is typically managed with renal angio-embolization. The development of a renal arteriopelvic fistula (APF) is an extremely rare complication, and accounts of haemorrhage from renal APF and its treatment have not been well-described in the literature. We successfully hypothesized that the ureteroscopic localization, fulguration, and closure with a fibrin sealant at the site of the arterial bleed results in optimal treatment for this clinical presentation. We report this case in detail. Promising Future Implications The successful and cost-effective endoscopic approach described here for treatment of post-PCNL renal APF and unremitting gross hematuria ought to be considered as an adjunct to renal angiography and embolization when the source of bleeding cannot be accurately identified using traditional imaging modalities. .

Are physicians performing neonatal circumcisions well-trained?

INTRODUCTION: Notwithstanding the recommendations from the Canadian Pediatric Association and the American Academy of Pediatrics on the indications for neonatal circumcision, this procedure is still common in North America and throughout the world. Our purpose is not to argue whether this procedure should be done, but rather to examine who is doing it, their training, how it is performed and how can we prevent unsatisfactory results and complications. The objective is to identify what fields of knowledge require improvement and then design a teaching module to improve the outcomes of neonatal circumcision. METHODS: A 19-question cross-sectional survey, including a visual identification item, was submitted to 87 physicians who perform neonatal circumcisions in Southwestern Ontario, Canada. To improve our response rate, study subjects were contacted in a variety of ways, including mail and fax and telephone. Once the survey was completed, we produced a surgical technique training video on using the Gomco clamp and the Plastibell techiques. A knowledge dissemination workshop was held with survey participants to discuss contraindications and the use of anesthesia and management of complications of neonatal circumcision and to evaluate the surgical technique training video. A 6-month follow-up questionnaire was completed to determine the impact of the teaching course on participants' daily practice. RESULTS: In total, we received 54 responses (62% response rate). From these, 46 (85%) were family doctors and pediatricians, while the remaining 8 (15%) were pediatric general surgeons and urologists. The circumcisions were carried out with the Gomco clamp 35 (63%) and the Plastibell 21 (37%). No respondent admitted to learning the procedure through a structured training course. Of the non-surgeons, 19 (43%) learned to perform a circumcision from a non-surgeon colleague. A little over a third of the participants (17, 31%) were happy to perform a circumcision in a child born with a concealed penis, where circumcision is contraindicated. With respect to the early complications post-circumcision, 8 (100%) surgeons versus 29 (63%) non-surgeons felt comfortable dealing with bleeding (p = 0.046). In total, 7 (88%) surgeons versus 16 (35%) non-surgeons were comfortable dealing with urinary retention (p = 0.01). Also, 8 (100%) surgeons versus 24 (52%) non-surgeons were comfortable dealing with a wound dehiscence (p = 0.02). Moreover, 6 (75%) surgeons and 5 (10%) non-surgeons were comfortable managing meatal stenosis (p < 0.01). Five (63%) surgeons versus 15 (33%) non-surgeons were confident in dealing with a trapped penis post-circumcision (p = 0.24). CONCLUSIONS: Our survey findings indicate that most physicians performing neonatal circumcisions in our community have received informal and unstructured training. This lack of formal instruction may explain the complications and unsatisfactory results witnessed in our pediatric urology practice. Many practitioners are not aware of the contraindications to neonatal circumcision and most non-surgeons perform the procedure without being able to handle common post-surgical complications. Based on our survey findings, we planned and carried out a formal training course to address these issues.

Buried penis: An unrecognized risk factor in the development of invasive penile cancer.

One of the documented benefits of neonatal circumcision is protection against invasive penile cancer. To date there have been a handful of published cases of invasive penile cancer in men circumcised as neonates. We report a case of a 73-year-old man, with a history of neonatal circumcision with no evidence of previous human papillomavirus exposure, who developed a buried penis secondary to obesity. He was diagnosed with Grade 2, pT3N0 squamous cell carcinoma of the penis. This report suggests that buried penis may pose a risk factor for the development of penile cancer despite the protective effects of neonatal circumcision. Thus periodic examination of a buried penis is warranted even in patients with no risk factors for penile cancer. A review of the literature is provided.

Emerging novel therapies in the treatment of castrate-resistant prostate cancer.

The treatment options for patients with castration-resistant prostate cancer (CRPC), until very recently, only included docetaxel. In the past 10 months, newly Federal Drug Administration (FDA) approved agents in the United States have shown survival benefit for patients with CRPC. This review takes a closer look at these newer agents: sipuleucel-T (immune therapy) and cabazi-taxel (cytotoxic therapy). We also review the evidence supporting the FDA's approval of denosumab (bone-targeted therapy) as a treatment option for men with CRPC and bony metastases. Newer agents currently being investigated in phase III clinical trials for their potential role in metastatic CRPC are also reviewed. These agents include abiraterone (hormonal therapy), TAK-700 (hormonal therapy), MDV3100 (hormonal therapy), ipilimumab (immune therapy), zibotentan (endothelin-A receptor antagonist) and dasatinib (tyrosine kinase inhibitor). As ongoing studies using all the aforementioned agents continue to evolve, our understanding of how and where these agents fit into the treatment paradigm for patients with CRPC will become clearer.

Scrotal syringocystadenoma papilliferum: case report.

Syringocystadenoma papilliferum (SCAP) is a benign rare adnexal skin neoplasm, which in a third of cases arises from a nevus sebaceous and is most commonly found on the head and neck and in very rare instances found on the genitalia. We report on a 59-year-old man with SCAP on the scrotum. The clinical scenario and histopathological findings are outlined. Following excision and histological confirmation of a noninfiltrative process, the patient remains asymptomatic. To our knowledge, only three other cases of such a lesion on the scrotum have been reported in the literature.