Androgen receptor expression is associated with adverse pathological features in ureteral but not in pelvicalyceal urothelial carcinomas of the upper urinary tract.

PURPOSE: This study aims to determine the significance of androgen receptor (AR) expression in urothelial carcinoma of the upper urinary tract (UTUC). METHODS: AR expression was assessed on tissue microarrays containing specimens of 737 patients with UTUC who underwent radical nephroureterectomy with curative intent. AR expression was correlated with clinical and pathological tumor features as well as recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). RESULTS: Overall, AR was expressed in 11 % of tumors. AR expression was significantly associated with tumor necrosis as well as sessile and multifocal tumor growth but not with RFS, CSS or OS. AR was detected nearly twice as often in tumors of the ureter than of the pelvicalyceal system (p = 0.005). Subgroup analyses showed that the significant associations of AR with unfavorable pathologic features were exclusively attributable to tumors located in the ureter. However, in both ureteral and pelvicalyceal tumors, AR status was independent of RFS, CSS and OS. CONCLUSIONS: In this cohort of patients treated with RNU, AR expression was found in approximately 10 % of UTUCs, twice as often in ureteral than in pelvicalyceal tumors. While AR expression had no impact on postoperative prognosis, it was significantly associated with unfavorable pathologic features in ureteral tumors. Steroid hormone signaling might be relevant for future investigations of differences between ureteral and pelvicalyceal tumors.

Salty, Sweet and Difficult to Treat: A Case of Profound Hypernatremia in the Setting of Hyperosmotic Hyperglycemic State.

Hyperosmolar hyperglycemic state (HHS) is a disorder that occurs most frequently in type 2 diabetics and is associated with high mortality - up to 50%. Hypernatremia, when associated with HHS, worsens the prognosis. Encephalopathy is evident at a serum sodium level greater than 160 mOsm/kg. Additional symptoms include lethargy, weakness, seizures, and coma. Rhabdomyolysis can rarely occur in hyperosmolar states. Here we describe a case of severe hypernatremia in the setting of HHS leading to profound encephalopathy and report to the best of our knowledge the highest serum sodium level published in the literature. A 50-year-old female with no past medical history (PMH) of diabetes presented to the ED obtunded and found to have a glucose level of 1400 mg/dL without metabolic acidosis or ketosis. Her sodium on presentation was 169 mOsm/kg but subsequently rose to 200 mOsm/kg when corrected for hyperglycemia. Plasma osmolality was 340 mOsm/kg. She developed pre-renal acute kidney injury (AKI) secondary to the osmotic diuresis from severe hyperglycemia as well as rhabdomyolysis with a peak creatine kinase(CK) level of 2493. The free water deficit was 14L which was corrected. New-onset anisocoria raised concern for osmotic demyelination which was further investigated with MRI. An acute ischemic stroke in the right caudate was found. Fortunately, the patient survived the endocrine emergency. This case emphasizes the importance of an appropriate rate of sodium correction. This case is particularly unique because the degree of hypernatremia seen here was in the absence of intentional salt loading (for example by the administration of hypertonic saline), or psychiatric disease (as psychogenic adipsia). In conclusion, we report the case of severe hypernatremia and the highest documented serum sodium level was seen in literature in the background of HHS, rhabdomyolysis and septic shock.

Primary Sinonasal Lymphoma: A Rare Cause of Cranial Neuropathies.

Primary sinonasal lymphomas are a rare type of non-Hodgkin lymphoma (NHL) with an overall incidence of about 1% of all head and neck cancers. Diffuse large B-cell lymphoma (DLBCL) is the most common type of NHL and it most commonly occurs in elderly men. The diagnosis of such a lymphoma is difficult because of its varied presentation, which usually occurs late after a significant mass effect has taken place. Symptoms vary significantly, from simply nasal obstruction or epistaxis to varied cranial neuropathies or the confusion seen with central nervous system (CNS) spread. Patients may present with a large orbital mass and proptosis. Therefore, emphasis should be placed on earlier detection by using appropriate imaging modalities to reveal such masses. A biopsy is necessary to confirm the diagnosis. The prognosis is scored by the International Prognostic Index. Staging scans with whole-body computed tomography (CT) with contrast and positron emission tomography-fluorodeoxyglucose (PET-FDG) are required to determine other areas of involvement. Treatment is with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) with the case-dependent use of intrathecal chemoprophylaxis (methotrexate) to prevent CNS spread. Here, we present a case series of two patients who were found to have a primary sinonasal lymphoma of the DLBCL type. In both cases, the presenting symptoms were vague. A high index of suspicion is required to diagnose NHL early on, which portends the best chance of a successful outcome. This article seeks to emphasize the role of including primary sinonasal lymphoma as a differential in the presentation of unrelenting cranial neuropathies or facial mass.

Reactive Perforating Collagenosis; An Uncontrolled Pruritus That Left You Scratching Your Head.

Acquired perforating collagenosis is a rare disease of altered collagen formation that is extruded through the epidermis. It is most commonly seen in patients with microvascular disease including longstanding diabetes and chronic kidney disease (CKD). Due to the rarity of the disease, no large randomized clinical studies have been performed to determine the most efficacious method of treatment. Therefore, most of the knowledge available for treatment is secondary to the information collected through case reports, case series, and retrospective analyses. In this report, we present the case of a 68-year-old male with history of stage IV CKD who presented with a severe skin rash that was present over his body, including the chest, arms, back, neck, and buttocks. It did not involve the mouth, legs, palms or soles of the feet. He did not have a significant history of diabetes and had been placed on steroids with the concern that this rash may have been secondary to a drug reaction, erythema multiforme, or bullous pemphigoid. Two skin biopsies were performed as the patient was not responding to systemic and topical steroid or oral antibiotic therapy. The final biopsy ultimately revealed a diagnosis of acquired perforating collagenosis. This is unusual in our case because although our patient had advanced CKD, he was not on dialysis, and had no significant longstanding history of diabetes. Additionally, as the prevalence of CKD is increasing in the population, it becomes more pertinent for providers to be aware of dermatological conditions associated with advanced CKD. This case report seeks to raise awareness of this disease. Furthermore, as the initial skin biopsy was unrevealing, this case also emphasizes the importance of repeating a biopsy to reduce the chance of sampling error.

Maintaining focus on administering effective malaria treatment during the COVID-19 pandemic.

As September marks the start of the malaria season in South Africa (SA), it is essential that healthcare professionals consider both COVID- 19 and malaria when a patient who lives in or has recently travelled to a malaria area presents with acute febrile illness. Early diagnosis of malaria by either a rapid diagnostic test or microscopy enables prompt treatment with the effective antimalarial, artemether-lumefantrine, preventing progression to severe disease and death. Intravenous artesunate is the preferred treatment for severe malaria in both children and adults. Adding single low-dose primaquine to standard treatment is recommended in endemic areas to block onward transmission. Use of the highly effective artemisinin-based therapies should be limited to the treatment of confirmed malaria infections, as there is no clinical evidence that these antimalarials can prevent or treat COVID-19. Routine malaria case management services must be sustained, in spite of COVID-19, to treat malaria effectively and support SA's malaria elimination efforts.

A Rare Cause of Bilateral Corneal Ulcers: Vitamin A Deficiency in the Setting of Chronic Alcoholism.

Vitamin A deficiency is rarely encountered in the western world. When encountered, vitamin A deficiency is seen as a component of the malabsorption spectrum of disease. Given the infrequency of nutritional deficits in the developed world, vitamin A-associated ophthalmologic disease is rarely encountered. We report a case of a 56-year-old male with severe vitamin A deficiency in the setting of alcoholic liver cirrhosis. This case emphasizes two important points. First, it considers vitamin A deficiency as a cause of corneal ulceration in patients with chronic alcoholism. Second, it raises awareness of hepatotoxicity that can result after the supplementation of vitamin A in patients with chronic alcoholism. Although an uncommon diagnosis, it should be considered when other causes, such as infectious and autoimmune conditions, are ruled out.

Varicella-Zoster Meningitis With Hypoglycorrhachia in an Immunocompetent Patient Presenting With Disseminated Varicella-Zoster Infection.

Varicella-zoster virus (VZV) infection is rarely reported in immunocompetent hosts. We report the case of a 40-year-old male who presented with altered mental status. One week prior, he was seen at his outpatient physician's office for a rash along the lateral right thigh. Erythema of the right gluteal region was noted, but no vesicles were present. He was treated for shingles rash with acyclovir with improvement. After a period of initial improvement in the rash, the patient developed a persistent headache. Given his migraine history, he overlooked the headache. He then developed fever, followed by confusion and was brought to the ED for further evaluation. CT head was unremarkable. Lumbar puncture revealed aseptic meningitis. This case highlights the unusual presentation of disseminated VZV infection in an immunocompetent host. It stresses the importance of maintaining high suspicion for disseminated VZV infection despite the patient being immunocompetent.

Mucosal Melanoma: A Rare Entity and Review of the Literature.

Mucosal melanoma is a rare variant of melanoma representing around 1% of total cases of melanoma diagnosed. The usual sites of mucosal involvement are the sino-nasal passages, the oral cavity, and less commonly the upper gastrointestinal (GI) tract. It also has been reported to occur in vulvovaginal and anorectal mucosa.  We present a rare case of mucosal melanoma that presented as recurrent epistaxis, headache, and sinus pressure. CT maxillofacial imaging revealed a large mass right nasal cavity. This was biopsied by ENT and shown to be mucosal melanoma. This was treated with palliative radiation followed by immunotherapy with nivolumab.  Along with details of the case, we also discuss current treatment options with a focus on the role of immunotherapy and its efficacy in cases of head and neck mucosal melanoma. Our review of literature supports use of combination immunotherapy (including both nivolumab and ipilimumab) as it shows greater efficacy than either therapy alone. When combined with radiation therapy (RT) the overall response rate is improved and RT induces an abscopal effect; where benefits of RT are also seen at nonirradiated locations.  In our patient, the use of radiation was essentially palliative as the patient was deemed to not be a surgical candidate. We discuss in our literature review the optimum timing of radiation in relation to definitive surgery or immunotherapy.

Implementing malaria control in South Africa, Eswatini and southern Mozambique during the COVID-19 pandemic.

The COVID-19 pandemic has strained healthcare delivery systems in a number of southern African countries. Despite this, it is imperative that malaria control and elimination activities continue, especially to reduce as far as possible the number and rate of hospitalisations caused by malaria. The implementation of enhanced malaria control/elimination activities in the context of COVID-19 requires measures to protect healthcare workers and the communities they serve. The aim of this review is therefore to present innovative ideas for the timely implementation of malaria control without increasing the risk of COVID-19 to healthcare workers and communities. Specific recommendations for parasite and vector surveillance, diagnosis, case management, mosquito vector control and community outreach and sensitisation are given.

Chilaiditi's Sign: A Case Report.

Chilaiditi's sign refers to the interposition of the colon (usually the transverse colon) between the diaphragm and the liver. When associated with abdominal pain it is referred to as Chilaiditi's syndrome. Chilaiditi's sign is rare entity with an estimated incidence of 0.025 to 0.28% worldwide. The sign occurs more frequently in males, with a male to female ratio of 4:1. Apparent pneumoperitoneum seen on imaging below the right hemidiaphragm, a life-threatening condition, may in fact be merely Chilaiditi's sign. Awareness of this phenomenon and its consideration as a differential diagnosis is essential to prevent unnecessary laparoscopic intervention. Here we present a case of a 74-year-old male who was incidentally found to have free air under the diaphragm without symptoms of abdominal pain. After further evaluation by the radiologists and surgeons it was concluded that he had Chilaiditi's sign and no further intervention was required. However, due to the lack of awareness of this radiographic finding patients can be subjected to unnecessary surgical intervention.

What factors influence the results of coronary artery bypass grafting in aged patients?

AIM: Early and late results were studied in order to improve the indication for coronary artery bypass grafting (CABG) and to enhance METHODS: A total of 1 973 patients aged 70 years and older who had undergone isolated CABG were studied. Elective operations (EL) were performed in 1 716 patients and 257 patients underwent urgent or emergency operations (UR/EM). Patients were divided into two groups; 104 patients aged 80 years and older (Oct. Group) and 1 869 patients of septuagenarians (Sept. Group). There were no differences between the groups in the number of diseased vessels. RESULTS: Total operative mortality rates in the Oct. and the Sept. groups were 7% and 4%, respectively. The operative mortality of elective surgery was 4% in both groups. The operative mortality of UR/EM CABG was significantly higher in the Oct. group than in the Sept. group (21% vs 6%). Operative mortality was significantly higher in patients with preoperative poor (<49%) left ventricular ejection fraction (LVEF) than in patients with higher (>50%) LVEF (6% vs 3%). Among preoperative risk factors, diabetes mellitus and peripheral vascular disease were significant contributory factors to operative death. In the follow-up study, 70% patients of the Oct. group and 72% patients of the Sept. group survived. Preoperative number of diseased vessels and number of CABG grafts did not influence the early and late CONCLUSION: Preoperative poor LVEF, diabetes mellitus and peripheral vascular disease were significant contributory factors to operative death. When feasible, CABG in octogenarians should be performed electively.

Passive ventricular constraint amends the course of heart failure: a study in an ovine model of dilated cardiomyopathy.

OBJECTIVE: Dilated cardiomyopathy (DCM) is associated with a progressive deterioration in cardiac function. We hypothesised that some of the deleterious effects of DCM could be reduced by mechanically limiting the degree of cardiac dilatation. METHODS: A Transonic 20A cardiac output (CO) flow-probe was implanted in the pulmonary artery of 12 adult (52 +/- 4 kg) sheep. Early heart failure was created by rapid right ventricular (RV) pacing for 21 days at a rate which resulted in an initial 10% decrease in CO (to a maximum of 190 bpm). A custom polyester jacket (Acorn Cardiovascular, St Paul, MN) was then placed, via a partial lower sternotomy, on the ventricular epicardium of all sheep. Animals were randomised either to jacket retention (wrap) or removal (sham). Pacing was recommenced at a higher rate (that initiated a further 10% decrease in CO) for 28 days. Haemodynamic and echocardiographic parameters were determined at baseline, implant and at termination. RESULTS: At termination, the left ventricular fractional shortening was significantly higher (p = 0.03), the degree of mitral valve regurgitation lower (scaled 0-3) (p = 0.03) and the left ventricular long axis area smaller (p = 0.02) in the wrap animals compared with sham. CONCLUSIONS: In this model of heart failure, ventricular constraint with a polyester jacket diminished the deterioration in cardiac function associated with progressive dilated cardiomyopathy. These results suggest that maintainance of a more normal cardiac size and shape may be beneficial in patients with dilated cardiomyopathy.

A second-generation enzyme immunoassay for detection of antibodies to IFN-alpha.

We have developed a solid-phase enzyme-linked immunoassay (EIA) for detecting antibodies to interferon-alpha2 (IFN-alpha2) in serum or plasma. In this assay, based on the sandwich principle, the capture antigen, IFN-alpha2, is covalently bound to the wells in 96-well plates. This novel procedure offers considerable advantages over the antigen binding by passive adsorption used in most previous EIA. Specific antibodies present in clinical specimens bind to the anchored antigen and are detected by adding peroxidase-labeled IFN-alpha2 and a peroxidase substrate mixture. The resultant color is a function of the concentration of antibody in the sample. The assay has proved to be convenient, precise, and reproducible and can detect as little as 1-5 ng/ml of specific antibody IgG.

Outcome of geometric endoventricular repair in impaired left ventricular function.

BACKGROUND: Traditionally, repair of left ventricular aneurysms has been limited to patients with large localized ventricular aneurysms. Repair of dyskinetic segments in the setting of poor left ventricular function is still contentious. METHODS: Forty patients underwent geometric endoventricular repair, a new technique of ventricular aneurysm repair, over a 2-year period. Two groups of patients undergoing coronary artery bypass grafting (CABG) for left ventricular dysfunction in the same time period were reviewed. Group 1 comprised 23 consecutive patients who underwent geometric endo-ventricular repair along with CABGs, whereas group II consisted of 22 patients who underwent CABG alone. RESULTS: The early mortality was 9.1% in group I (1 cardiac, 1 noncardiac) and 0 in group II (NS). New York Heart Association class was remarkably improved from 3.4 to 1.4 (p < 0.05) in group I and to a lesser extent in group II (3.7+/-0.5 versus 2.3+/-0.5). Diastolic dimension of left ventricle was significantly reduced from 5.6 cm to 4.4 cm (p < 0.05) in group I and virtually unchanged in group II. There was one late death in each of the groups. CONCLUSIONS: This technique of geometric left ventricular aneurysm repair is useful in patients with dyskinetic segments and may help in reducing cardiac size.

Geometric endo-ventricular patch repair of inferior left ventricular scars improves mitral regurgitation and clinical outcome.

BACKGROUND: The surgical reconstruction of inferior left ventricular (LV) aneurysms and scars has been considered a difficult procedure and there has been little material published about this treatment option. In this study we report on our experience with reconstruction of the inferior wall and compare it to the outcome of anterior LV reconstructions. METHODS: Seventeen patients (group 1) underwent geometric endo-ventricular patch repair (GER) of inferior LV aneurysms and dyskinetic scars between January 1998 and December 2000. In addition to poor LV function, 5 of these patients had severe mitral valve regurgitation (MR), 8 had moderate MR, and 4 had mild MR preoperatively. These patients also underwent coronary artery bypass graft surgery or valve surgery. The perioperative course, survival, and clinical status were evaluated in this group and was compared to those of 86 patients (group 2) undergoing anterior GER during the same period. RESULTS: There was 1 early death in group 1 (5.8%) and 6 in group 2 (7%) (p = ns). At the conclusion of the operative procedure, all patients in group 1 were weaned off cardiopulmonary bypass with trivial to mild MR. There was 1 late death in group 1 (6.2%) and 2 in group 2 (2.8%) (p = ns). Eleven patients (73%) in group 1 were in New York Heart Association class 1 compared to 60 in group 2 (77%) (p = ns). Follow-up echocardiography showed that 80% of patients in group 1 had trivial MR. CONCLUSIONS: The surgical reconstruction of inferior LV aneurysms and scars can be performed safely with the expectation of a reasonable early outcome similar to that achieved with anterior LV scars. When used in this setting GER improves MR, reducing the likelihood of heart failure decompensation.

Combined endocardial and epicardial radiofrequency ablation of right and left atria in the treatment of atrial fibrillation.

BACKGROUND: The maze procedure and its modifications have been successful in treating atrial fibrillation (AF), at the expense of longer procedure times and increased morbidity. This study evaluated the early results of using radiofrequency ablation as a surgical adjunct in treating AF. METHODS: Twenty-six patients, with established or frequent intermittent AF, who were undergoing various cardiac surgical procedures, were enrolled. During their operations, the patients underwent intraoperative left and right atrial radiofrequency ablation lesions using a handheld flexible probe. Patients were followed up with echocardiography and Holter monitoring. RESULTS: All 26 patients were weaned off cardiopulmonary bypass in sinus rhythm. There were 2 early noncardiac deaths in high-risk patients; 23 surviving patients (95%) remained in sinus rhythm at a mean follow-up of 175 days (range 96 to 400 days). Three patients were defibrillated into sinus rhythm 30, 40, and 60 days after their operation. Test epicardial lesions on the right atrial appendage in 12 patients showed full-thickness coagulation of tissue in 10 (83%). CONCLUSIONS: A combined endocardial and epicardial set of radiofrequency lesions in both atria abolished AF in most patients at 6 months and facilitated easy conversion of recurrent AF into sinus rhythm. The transmural nature of the epicardial lesions has implications for further development.

Homograft aortic root replacement to correct infective endocarditis requiring seven open cardiac procedures.

Infective endocarditis, presumably from a septic dental focus, affecting the aortic valve was seen as acute aortic regurgitation in a 20-year-old woman. Seven open cardiac procedures for replacement of the aortic valve and left ventricular outflow tract were performed over the subsequent 6 years. Aortic root replacement using a fresh antibiotic-sterilized homograft was performed as the last definitive operative procedure. This article is presented to highlight (1) the use of homograft aortic root replacement for extensive involvement of aortic valve and left ventricular outflow tract in cases of infective endocarditis and (2) the feasibility of multiple sternal reentries when indicated.

Exclusive Y graft operation for multivessel coronary revascularization.

BACKGROUND: The pedicled (in-situ) left internal mammary artery grafted to the left anterior descending artery has a very high late patency and reduces late mortality following coronary artery bypass surgery. A technique is described which achieves total arterial revascularization in patients with multivessel coronary disease and which is also entirely pedicled. METHODS: Using the left internal mammary artery and radial artery joined as a composite Y graft, all coronary territories may be grafted. RESULTS: One in-hospital death from 464 patients (0.2%) occurred. Age (mean +/- standard error) was 64.7 +/- 0.5 years and number of distal anastomoses 3.4 +/- 0.04. Of 1,681 patients from Royal Melbourne Hospital, 346 had this operation. Comparison found no preoperative selection bias and no postoperative differences in complications. Actuarial survival was 0.98 +/- 0.01 at 36.1 +/- 0.3 months. CONCLUSIONS: Total arterial revascularization may be performed using the left internal mammary artery and radial artery as a composite Y graft. There was no increase in complications. This technique preserves the left internal mammary artery to left anterior descending artery graft.