Increased Intact Proinsulin in the Oral Glucose Challenge Sample is an Early Indicator for Future Type 2 Diabetes Development - Case Reports and Evidence from the Literature.

BACKGROUND: Increased intact proinsulin in plasma is a highly specific biomarker for a major disruption of insulin-processing in the pancreatic ß-cells with associated insulin resistance. Increased intact proinsulin in morning fasting plasma indicates not only incipient diabetes, but also increased risk of macrovascular events in the patient - of ten times before an actual diagnosis of diabetes - due to the convergence of ß-cell dysfunction, insulin resistance, and chronic systemic inflammation. This has raised the question as to whether a marked increase in intact proinsulin levels after oral glucose load in healthy subjects might be considered as indicative for ß-cell dysfunction and prediabetes. METHODS: A previous study from 2011 examined, inter alia, intact proinsulin levels in blood samples from twenty healthy study participants at baseline and two hours after an oral glucose tolerance test (OGTT) with 75 g glucose. Seventeen of the participants showed normal glucose levels at baseline and at two hours compared to 4 participants with normal intact proinsulin levels at baseline but increased intact proinsulin levels at two hours. RESULTS: All four patients went on to develop type 2 diabetes in the following 5 years. None of the other subjects from the previous investigation developed type 2 diabetes. CONCLUSIONS: As also confirmed by recent literature, intact proinsulin provides a powerful, easily measured biomarker for ß-cell dysfunction and insulin resistance in type 2 diabetes, as well as risk of future cardiovascular events regardless of the stage of diabetes.

Chondroblastoma-like Osteosarcoma.

CONTEXT.­: Chondroblastoma-like osteosarcoma is an exceedingly rare variant of osteosarcoma, with 22 cases reported in the English-language literature. The tumor is slightly more common in males, with a broad age range (from childhood to elderly). The most commonly involved bones are the metatarsus and tibia, followed by the femur. Most tumors have malignant or worrisome radiographic findings. Prognosis is variable, depending on the presence or absence of lung metastases, local recurrence, and probably tumor location. Histologically, chondroblastoma-like osteosarcoma is characterized by monotonous, minimally to moderately atypical rounded cells with ovoid nuclei resembling chondroblastoma, and abnormal osteoid deposition with destruction of the bone. OBJECTIVE.­: To review the clinical, radiographic, and histopathologic features of chondroblastoma-like osteosarcoma. DATA SOURCES.­: PubMed-published chondroblastoma-like osteosarcoma cases in the English-language literature. CONCLUSIONS.­: Although exceedingly rare, chondroblastoma-like osteosarcoma should be considered in the differential diagnosis of chondroblastoma, especially in the presence of radiologic findings suggestive of an aggressive lesion.

Effects of Periodic Intensive Insulin Therapy: An Updated Review.

BACKGROUND: Traditional insulin treatment for diabetes mellitus with insulin administered subcutaneously yields nonpulsatile plasma insulin concentrations that represent a fraction of normal portal vein levels. Oral hypoglycemic medications result in the same lack of pulsatile insulin response to blood glucose levels. Intensive treatments of significant complications of diabetes are not recommended due to complicated multidrug regimens, significant weight gain, and the high risk of hypoglycemic complications. Consequently, advanced complications of diabetes do not have an effective treatment option because conventional therapy is not sufficient. Intensive insulin therapy (IIT) simulates normal pancreatic function by closely matching the periodicity and amplitude of insulin secretion in healthy subjects; however, the mechanisms involved with the observed improvement are not clearly understood. OBJECTIVE: The current review aims to analyze the pathophysiology of insulin secretion, discuss current therapies for the management of diabetes, provides an updates on the recent advancements of IIT, and proposes its mechanism of action. METHODS: A literature search on PubMed, MEDLINE, Embase, and CrossRef databases was performed on multiple key words regarding the history and current variations of pulsatile and IIT for diabetes treatment. Articles reporting the physiology of insulin secretion, advantages of pulsatile insulin delivery in patients with diabetes patients, efficacy and adverse effects of current conventional insulin therapies for the management of diabetes, benefits and shortcomings of pancreas and islet transplantation, or clinical trials on patients with diabetes treated with pulsed insulin therapy or advanced IIT were included for a qualitative analysis and categorized into the following topics: mechanism of insulin secretion in normal subjects and patients with diabetes and current therapies for the management of diabetes, including oral hypoglycemic agents, insulin therapy, pancreas and islet transplantation, pulsed insulin therapy, and advances in IIT. RESULTS: Our review of the literature shows that IIT improves the resolution of diabetic ulcers, neuropathy, and nephropathy, and reduces emergency room visits. The likely mechanism responsible for this improvement is increased insulin sensitivity from adipocytes, as well as increased insulin receptor expression. CONCLUSIONS: Recent advancements show that IIT is an effective option for both type 1 diabetes mellitus and type 2 diabetes mellitus patient populations. This treatment resembles normal pancreatic function so closely that it has significantly reduced the effects of relatively common complications of diabetes in comparison to standard treatments. Thus, this new treatment is a promising advancement in the management of diabetes. (Curr Ther Res Clin Exp. 2019; 80:XXX-XXX).

Race-associated expression of MHC class I polypeptide-related sequence A (MICA) in prostate cancer.

Despite the lack of a complete understanding of the disparities involved, prostate cancer (PCa) has both higher incidence and death rates in African American Men (AAM) relative to those of Caucasian American Men (CAM). MHC class I polypeptide related sequence A (MICA) is an innate immunity protein involved in tumor immunoevasion. Due to a lack of reports of race-specific expression of MICA in PCa, we evaluated MICA expression in patients' tumors and in cell lines from a racially diverse origin. Immunohistochemistry was done on a tissue microarray (TMA) with antibodies against MICA. Tumor MICA mRNA was assessed by data mining using Oncomine and PROGeneV2. Surface MICA and release rate of soluble (s) MICA was evaluated in PCa cell lines originally derived from African American (MDA-PCa-2b) or Caucasian (LNCaP and DU-145) PCa patients. Prostate tumor tissue had a 1.7-fold higher MICA expression relative to normal tissue (p < .0001). MICA immunoreactivity in PCa tissue from AAM was 24% lower (p = .002) compared to CAM. Survival analysis revealed a marginal association of low MICA with poor overall survival (OS) (p = .058). By data mining analysis, a 2.9-fold higher level of MICA mRNA was evidenced in tumor compared to normal tissue (p < .0001). Tumors from AAM had 24% lower levels of MICA mRNA compared to tumors from CAM (p = .038), and poor prognosis was found for patients with lower MICA mRNA (p = .028). By flow cytometry analysis, cell fraction positive for surface MICA was of 3% in MDA-PCa-2b cells, 54% in DU-145 cells, and 67% in LNCaP cells (p < .0001). sMICA was detected in DU-145 and LNCaP cells, but was not detected in MDA-PCa-2b cells. Both LNCaP and DU-145 cells were sensitive to cytolysis mediated by Natural killer (NK) cells. MDA-PCa-2b cells, however were between 1.3-fold at 10:1 Effector:Target (E:T) ratio (p < .0001) and 2-fold at 50:1 E:T ratio (p < .0001) more resistant to NK-mediated cytolysis relative to cells from Caucasian origin. These results suggest that MICA expression may be related to the aggressive nature of PCa. Our findings also demonstrate for the first time that there are variations in MICA expression in the context of racial differences. This study establishes a rationale for further investigation of MICA as a potential race-specific prognostic marker in PCa.

Cyto-histological correlation of Xp11.2 translocation/TFE3 gene fusion associated renal cell carcinoma: Report of a case with review of literature.

The MiT family translocation renal cell carcinomas (RCCs) are relatively rare in comparison to the conventional RCC. The cytologic features overlap with conventional clear cell RCC and papillary RCCs, thereby making the diagnosis extremely challenging. Here, we describe a case of TFE3 translocation associated RCC in a 58-year-old patient, with emphasis on cytomorphologic features and clues toward this diagnostic entity. Correlating the cytohistologic findings and review of touch imprints revealed that presence of hyaline nodules resembling leisegang rings and psammoma bodies in cytologic smears from kidney tumors serve as an important clue in raising a suspicion for the diagnosis of MiT family translocation RCCs.

Targeting MTA1/HIF-1α signaling by pterostilbene in combination with histone deacetylase inhibitor attenuates prostate cancer progression.

The metastasis-associated protein 1(MTA1)/histone deacetylase (HDAC) unit is a cancer progression-related epigenetic regulator, which is overexpressed in hormone-refractory and metastatic prostate cancer (PCa). In our previous studies, we found a significantly increased MTA1 expression in a prostate-specific Pten-null mouse model. We also demonstrated that stilbenes, namely resveratrol and pterostilbene (Pter), affect MTA1/HDAC signaling, including deacetylation of tumor suppressors p53 and PTEN. In this study, we examined whether inhibition of MTA1/HDAC using combination of Pter and a clinically approved HDAC inhibitor, SAHA (suberoylanilide hydroxamic acid, vorinostat), which also downregulates MTA1, could block prostate tumor progression in vivo. We generated and utilized a luciferase reporter in a prostate-specific Pten-null mouse model (Pb-Cre+ ; Ptenf/f ; Rosa26Luc/+ ) to evaluate the anticancer efficacy of Pter/SAHA combinatorial approach. Our data showed that Pter sensitized tumor cells to SAHA treatment resulting in inhibiting tumor growth and additional decline of tumor progression. These effects were dependent on the reduction of MTA1-associated proangiogenic factors HIF-1α, VEGF, and IL-1ß leading to decreased angiogenesis. In addition, treatment of PCa cell lines in vitro with combined Pter and low dose SAHA resulted in more potent inhibition of MTA1/HIF-1α than by high dose SAHA alone. Our study provides preclinical evidence that Pter/SAHA combination treatment inhibits MTA1/HIF-1α tumor-promoting signaling in PCa. The beneficial outcome of combinatorial strategy using a natural agent and an approved drug for higher efficacy and less toxicity supports further development of MTA1-targeted therapies in PCa.

Histiocytic Sarcoma in a Kidney Transplant Patient: A Case Report and Review of the Literature.

Objective. Histiocytic sarcoma (HS) is an aggressive neoplasm with only limited number of reported series of cases and rare case reports of occurrence as a posttransplant neoplastic disorder. The etiology and pathogenesis of the disease is unknown and the optimal treatment is still under investigation. We describe an unusual case of HS in a patient with a remote history of kidney transplant. Method and Results. A 54-year-old male with a remote history of renal transplantation under maintenance immunosuppression presented with features of sepsis. CT abdomen revealed multiple heterogeneous masses in bilateral native kidneys and liver and enlarged abdominal and retroperitoneal lymph nodes. Viral serology work-up was negative. Needle core biopsy revealed a highly undifferentiated neoplasm comprised of highly atypical large cells with eosinophilic to vacuolated cytoplasm and hemophagocytosis. Extended panel of immunohistochemistry proved histiocytic lineage for the tumor cells. The patient expired 2 weeks following the diagnosis. Conclusion. Our case along with three previously published case reports raised the possibility of HS as a treatment-related neoplasm or a posttransplantation neoplastic disorder in solid organ transplant recipients.

Acute oxalate nephropathy associated with orlistat.

BACKGROUND: Obesity is a major world-wide epidemic which has led to a surge of various weight loss-inducing medical or surgical treatments. Orlistat is a gastrointestinal lipase inhibitor used as an adjunct treatment of obesity and type 2 diabetes mellitus to induce clinically significant weight loss via fat malabsorption. CASE PRESENTATION: We describe a case of a 76-year-old female with past medical history of chronic kidney disease (baseline serum creatinine was 1.5-2.5 mg/dL), hypertension, gout and psoriatic arthritis, who was admitted for evaluation of elevated creatinine, peaking at 5.40 mg/dL. She was started on orlistat 120 mg three times a day six weeks earlier. Initial serologic work-up remained unremarkable. Percutaneous kidney biopsy revealed massive calcium oxalate crystal depositions with acute tubular necrosis and interstitial inflammation. Serum oxalate level returned elevated at 45 mm/l (normal <27). Timed 24-hour urine collection documented increased oxalate excretion repeatedly (54-96 mg/24 hour). After five renal dialysis sessions in eighth days she gradually regained her former baseline kidney function with creatinine around 2 mg/dL. Given coexisting proton-pump inhibitor therapy, only per os calcium-citrate provided effective intestinal oxalate chelation to control hyperoxaluria. CONCLUSIONS: Our case underscores the potential of medically induced fat malabsorption to lead to an excessive oxalate absorption and acute kidney injury (AKI), especially in subjects with pre-existing renal impairment. Further, it emphasizes the importance of kidney biopsy to facilitate early diagnosis and treatment.

Dietary pterostilbene is a novel MTA1-targeted chemopreventive and therapeutic agent in prostate cancer.

Overexpression of the epigenetic modifier metastasis-associated protein 1 (MTA1) is associated with aggressive human prostate cancer. The purpose of this study was to determine MTA1- targeted chemopreventive and therapeutic efficacy of pterostilbene, a natural potent analog of resveratrol, in pre-clinical models of prostate cancer. Here, we show that high levels of MTA1 expression in Pten-loss prostate cooperate with key oncogenes, including c-Myc and Akt among others, to promote prostate cancer progression. Loss-of-function studies using human prostate cancer cells indicated direct involvement of MTA1 in inducing inflammation and epithelial-to-mesenchymal transition. Importantly, pharmacological inhibition of MTA1 by pterostilbene resulted in decreased proliferation and angiogenesis and increased apoptosis. This restrained prostatic intraepithelial neoplasia (PIN) formation in prostate-specific Pten heterozygous mice and reduced tumor development and progression in prostate-specific Pten-null mice. Our findings highlight MTA1 as a key upstream regulator of prostate tumorigenesis and cancer progression. More significantly, it offers pre-clinical proof for pterostilbene as a promising lead natural agent for MTA1-targeted chemopreventive and therapeutic strategy to curb prostate cancer.

The potential cost-effectiveness of the Diamondback 360® Coronary Orbital Atherectomy System for treating de novo, severely calcified coronary lesions: an economic modeling approach.

BACKGROUND: Patients who undergo percutaneous coronary intervention (PCI) for severely calcified coronary lesions have long been known to have worse clinical and economic outcomes than patients with no or mildly calcified lesions. We sought to assess the likely cost-effectiveness of using the Diamondback 360(®) Orbital Atherectomy System (OAS) in the treatment of de novo, severely calcified lesions from a health-system perspective. METHODS AND RESULTS: In the absence of a head-to-head trial and long-term follow up, cost-effectiveness was based on a modeled synthesis of clinical and economic data. A cost-effectiveness model was used to project the likely economic impact. To estimate the net cost impact, the cost of using the OAS technology in elderly (⩾ 65 years) Medicare patients with de novo severely calcified lesions was compared with cost offsets. Elderly OAS patients from the ORBIT II trial (Evaluate the Safety and Efficacy of OAS in Treating Severely Calcified Coronary Lesions) [ClinicalTrials.gov identifier: NCT01092426] were indirectly compared with similar patients using observational data. For the index procedure, the comparison was with Medicare data, and for both revascularization and cardiac death in the following year, the comparison was with a pooled analysis of the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI)/Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trials. After adjusting for differences in age, gender, and comorbidities, the ORBIT II mean index procedure costs were 17% (p < 0.001) lower, approximately US$2700. Estimated mean revascularization costs were lower by US$1240 in the base case. These cost offsets in the first year, on average, fully cover the cost of the device with an additional 1.2% cost savings. Even in the low-value scenario, the use of the OAS is cost-effective with a cost per life-year gained of US$11,895. CONCLUSIONS: Based on economic modeling, the recently approved coronary OAS device is projected to be highly cost-effective for patients who undergo PCI for severely calcified lesions.

Follicular Thyroid Carcinoma Metastatic to the Kidney: Report of a Case with Cytohistologic Correlation.

Here we report a case of a 45-year-old female who underwent thyroidectomy for thyroid cancer and presented 20 years later with a left renal mass. CT-guided core biopsy was performed, and imprints and histologic sections of the biopsy showed cells resembling thyroid follicular cells with a background containing colloid. Immunohistochemistry revealed positivity for thyroglobulin and thyroid transcription factor 1, consistent with metastatic follicular thyroid carcinoma (FTC). The patient later underwent radical nephrectomy; histologic sections of the resected tumor revealed an encapsulated lesion morphologically similar to the biopsy specimen. Thyroid metastases to the kidney are extremely rare and are often detected during postthyroidectomy surveillance by elevation in thyroid hormone levels, (131)I scintigraphy, or (18)F-fluorodeoxyglucose uptake in positron emission tomography studies. Treatment involves total thyroidectomy, resection of the metastatic foci, and (131)I therapy. The differential diagnoses of renal metastasis of FTC include the encapsulated follicular variant of papillary thyroid carcinoma (PTC), which possesses some of the nuclear features seen in conventional PTC but may occasionally be indistinguishable from FTC in cytologic preparations, and renal lesions such as benign thyroidization of the kidney and thyroid-like follicular carcinoma of the kidney, which mimic FTC in histologic appearance but do not stain with thyroid markers.

The clinical and cost burden of coronary calcification in a Medicare cohort: An economic model to address under-reporting and misclassification.

BACKGROUND: Coronary artery calcification (CAC) is a well-established risk factor for the occurrence of adverse ischemic events. However, the economic impact of the presence of CAC is unknown. OBJECTIVES: Through an economic model analysis, we sought to estimate the incremental impact of CAC on medical care costs and patient mortality for de novo percutaneous coronary intervention (PCI) patients in the 2012 cohort of the Medicare elderly (≥65) population. METHODS: This aggregate burden-of-illness study is incidence-based, focusing on cost and survival outcomes for an annual Medicare cohort based on the recently introduced ICD9 code for CAC. The cost analysis uses a one-year horizon, and the survival analysis considers lost life years and their economic value. RESULTS: For calendar year 2012, an estimated 200,945 index (de novo) PCI procedures were performed in this cohort. An estimated 16,000 Medicare beneficiaries (7.9%) were projected to have had severe CAC, generating an additional cost in the first year following their PCI of $3500, on average, or $56 million in total. In terms of mortality, the model projects that an additional 397 deaths would be attributable to severe CAC in 2012, resulting in 3770 lost life years, representing an estimated loss of about $377 million, when valuing lost life years at $100,000 each. CONCLUSIONS: These model-based CAC estimates, considering both moderate and severe CAC patients, suggest an annual burden of illness approaching $1.3 billion in this PCI cohort. The potential clinical and cost consequences of CAC warrant additional clinical and economic attention not only on PCI strategies for particular patients but also on reporting and coding to achieve better evidence-based decision-making.

Epigenetic potential of resveratrol and analogs in preclinical models of prostate cancer.

Lifestyle, particularly diet, is a risk factor for prostate cancer. Dietary polyphenols such as resveratrol possess anticancer properties and therefore have chemopreventive and therapeutic potential. Resveratrol has pleiotropic effects, exerting its biological activity through multiple pathways and targets, including those associated with cancer. Numerous studies have demonstrated the anticancer effects of resveratrol and, to a lesser extent, its analogs, in tissue culture, while in vivo observations are limited. Here, we provide a concise summary of our results on epigenetic mechanisms of resveratrol and analogs mediated through regulation of chromatin modifier metastasis-associated protein 1 (MTA1) and microRNAs (miRNAs), and highlight the anticancer effects of these compounds in preclinical models of prostate cancer. We suggest that the identified stilbene responsive mechanism-based biomarkers, such as MTA1 and oncogenic miRNAs, may become indicative of treatment efficacy in prostate cancer. Resveratrol analogs with better bioavailability, conferring superior pharmacological potencies and greater anticancer effects, may become stronger candidates for clinical development.

Allelic Variants in Arhgef11 via the Rho-Rock Pathway Are Linked to Epithelial-Mesenchymal Transition and Contributes to Kidney Injury in the Dahl Salt-Sensitive Rat.

Previously, genetic analyses identified that variants in Arhgef11 may influence kidney injury in the Dahl salt-sensitive (S) rat, a model of hypertensive chronic kidney disease. To understand the potential mechanism by which altered expression and/or protein differences in Arhgef11 could play a role in kidney injury, stably transduced Arhgef11 knockdown cell lines as well as primary cultures of proximal tubule cells were studied. Genetic knockdown of Arhgef11 in HEK293 and NRK resulted in reduced RhoA activity, decreased activation of Rho-ROCK pathway, and less stress fiber formation versus control, similar to what was observed by pharmacological inhibition (fasudil). Primary proximal tubule cells (PTC) cultured from the S exhibited increased expression of Arhgef11, increased RhoA activity, and up regulation of Rho-ROCK signaling compared to control (small congenic). The cells were also more prone (versus control) to TGFß-1 induced epithelial-mesenchymal transition (EMT), a hallmark feature of the development of renal interstitial fibrosis, and characterized by development of spindle shape morphology, gene expression changes in EMT markers (Col1a3, Mmp9, Bmp7, and Ocln) and increased expression of N-Cadherin and Vimentin. S derived PTC demonstrated a decreased ability to uptake FITC-albumin compared to the small congenic in vitro, which was confirmed by assessment of albumin re-uptake in vivo by infusion of FITC-albumin and immunofluorescence imaging. In summary, these studies suggest that genetic variants in the S form of Arhgef11 via increased expression and/or protein activity play a role in promoting kidney injury in the S rat through changes in cell morphology (Rho-Rock and/or EMT) that impact the function of tubule cells.

Pigmented Epithelioid Angiomyolipoma of the Kidney.

Extensive melanin pigment in an epithelioid angiomyolipoma, a potentially malignant and locally aggressive renal tumor, has been rarely reported. A 53-year-old, asymptomatic man with no significant past medical history underwent partial nephrectomy for a right kidney mass discovered on CT scan. Grossly, the mass was 4 cm, well-circumscribed, dark, brown-black. Microscopically, nests of large, clear-to-eosinophilic cells with mildly atypical, vesicular nuclei and prominent nucleoli were separated by striking vascular network. Abundant, brown-black, coarsely granular pigment was noted. The tumor stained with HMB-45 and MART-1 and was negative for broad spectrum cytokeratin, CK-7, CD-10, RCC antigen, EMA, vimentin, SMA, desmin, synaptophysin, chromogranin, and S 100. Fontana-Masson stain confirmed presence of melanin. Thick-walled vessels, spindle cells, and fat were absent. The patient had no family history of tuberous sclerosis. Close follow-up was recommended. It is important to differentiate this entity from melanoma, pigmented renal cell carcinoma, and pigmented paraganglioma.

Standardized Outcome Measurement for Patients With Coronary Artery Disease: Consensus From the International Consortium for Health Outcomes Measurement (ICHOM).

BACKGROUND: Coronary artery disease (CAD) outcomes consistently improve when they are routinely measured and provided back to physicians and hospitals. However, few centers around the world systematically track outcomes, and no global standards exist. Furthermore, patient-centered outcomes and longitudinal outcomes are under-represented in current assessments. METHODS AND RESULTS: The nonprofit International Consortium for Health Outcomes Measurement (ICHOM) convened an international Working Group to define a consensus standard set of outcome measures and risk factors for tracking, comparing, and improving the outcomes of CAD care. Members were drawn from 4 continents and 6 countries. Using a modified Delphi method, the ICHOM Working Group defined who should be tracked, what should be measured, and when such measurements should be performed. The ICHOM CAD consensus measures were designed to be relevant for all patients diagnosed with CAD, including those with acute myocardial infarction, angina, and asymptomatic CAD. Thirteen specific outcomes were chosen, including acute complications occurring within 30 days of acute myocardial infarction, coronary artery bypass grafting surgery, or percutaneous coronary intervention; and longitudinal outcomes for up to 5 years for patient-reported health status (Seattle Angina Questionnaire [SAQ-7], elements of Rose Dyspnea Score, and Patient Health Questionnaire [PHQ-2]), cardiovascular hospital admissions, cardiovascular procedures, renal failure, and mortality. Baseline demographic, cardiovascular disease, and comorbidity information is included to improve the interpretability of comparisons. CONCLUSIONS: ICHOM recommends that this set of outcomes and other patient information be measured for all patients with CAD.

Resolution of C1q deposition but not of the clinical nephrotic syndrome after immunomodulating therapy in focal sclerosis.

BACKGROUND: The natural evolution of C1q nephropathy (C1qNP) during immunosuppressive treatment is relatively little studied or understood. CASE PRESENTATION: A 30 year-old Caucasian female was referred to us for further management of biopsy-proven C1qNP and severe nephrotic syndrome. Serologic work-up remained negative, including complement C3 and C4 levels and repeated testing for antinuclear antibodies. A renal biopsy revealed minimal change nephropathy vs. focal sclerosis on light microscopy and C1qNP on immunopathology. She has failed trials of high-dose oral prednisone, mycophenolate mofetil 1,500 mg twice a day and a subsequent regimen of monthly IV cyclophosphamide 750 mg × 9 cycles. She also received the maximum tolerated angiotensin-converting enzyme inhibitor and spironolactone therapy. Random urine protein-to-creatinine (UPC) ratio predicted proteinuria in the range between 5-35 gm/day, while serum creatinine rose progressively from 1.0 mg/dL to 1.4 mg/dL (to convert to µmol/L, multiply by 88.4). A decision was made to repeat renal biopsy to reassess the underlying histology. The biopsy revealed focal sclerosis but no C1q deposition. CONCLUSIONS: Our case illustrates at least two points: first, an established pathologic diagnosis does not obviate the need for repeated renal biopsy later on, should diagnostic uncertainty persist. Second, histological diagnoses may evolve over time, especially in a patient receiving active and powerful immune-modulating treatment. In our case, the clinical nephrosis did not change with immunosuppressive therapy while C1q deposition ceased, making this latter entity likely the immunologically mediated process.

Cytomegalovirus colitis in a critically ill, dialysis-dependent, acute kidney injury patient without immunosuppressive therapy.

BACKGROUND: Historically, cytomegalovirus (CMV) infection in immunocompetent patients has been considered to have a relatively indolent and self-limited course, not warranting specific treatment. CASE PRESENTATION: We are presenting a 72-year-old African-American male transferred to our intensive care unit (ICU) with methicillin-resistant Staphylococcus aureus bacteremia, respiratory failure, and dialysis-dependent acute kidney injury. While he recovered from bacteremia, he remained difficult to wean from respiratory support, had labile blood pressure, and manifested persistent diarrhea. Stool antigen testing for C. difficile colitis returned repeatedly negative. Flexible sigmoidoscopy described diffuse ulceration, attributed to ischemic colitis. The colon biopsy specimen, however, described tissue-invasive cytomegalovirus (CMV) infection. Polymerase chain reaction (PCR) testing confirmed viremia with 8,900 copies/mL viral DNA. Human immunodeficiency virus antibody and PCR testing were both negative. Absolute lymphocyte count varied between 80 and 450/mm3 during the admission. After IV ganciclovir initiation, diarrhea and respiratory failure resolved, while renal function recovered to the patient'€™s baseline. CONCLUSION: The combination of critical illness and recent bacteremia likely represented a state of profound immunosuppression in this formerly healthy patient. CMV colitis may be under-diagnosed in sick ICU patients with renal failure and otherwise unexplained diarrhea. Serum PCR testing may aid the diagnosis.

Primary renal sclerosing epithelioid fibrosarcoma: report of 2 cases with EWSR1-CREB3L1 gene fusion.

We report the first 2 genetically confirmed cases of primary renal sclerosing epithelioid fibrosarcoma (SEF), occurring in a 17-year-old boy and a 61-year-old woman. In both cases, the tumors demonstrated the typical epithelioid clear cell morphology associated with extensive hyalinizing fibrosis, raising the differential diagnosis of solitary fibrous tumor, metanephric stromal tumor, and the sclerosing variant of clear cell sarcoma of the kidney. Both neoplasms demonstrated diffuse immunoreactivity for MUC4, a highly specific marker for SEF, and both demonstrated evidence of rearrangement of both the EWSR1 and CREB3L1 genes, which have recently been shown to be fused in this entity. Both neoplasms presented with metastatic disease. Primary renal SEF represents yet another translocation-associated sarcoma now shown to arise primarily in the kidney.

Cystic adenomatoid tumor of the uterus.

We present a case of a cystic adenomatoid tumor in a 40-year-old woman. The tumor was an intramural multicystic mass, histologically similar to a multicystic mesothelioma. Cystic adenomatoid tumors of the uterus are extremely rare. They present with a wide differential diagnosis in radiology. The tumors are known to be benign and awareness of this rare entity is the key to its diagnosis for a pathologist.