Predictive Value of Pleural Cytology in the Diagnosis of Complicated Parapneumonic Effusions and Empyema Thoracis.

INTRODUCTION: Complicated parapneumonic effusions (CPE) are distinguished from uncomplicated parapneumonic effusions (UPE) by the ability to resolve without drainage. Determinants include pleural pH, pleural glucose, and pleural LDH, along with microbiologic cultures. Inflammation mediated by neutrophil chemotactic cytokines leads to fibrinous loculation of an effusion, and the degree of this inflammation may lead to a CPE. One role of the pathologist is to evaluate for the presence of malignancy in a pleural effusion; however, the ability of the pathologist to distinguish a CPE from UPE has not been evaluated. MATERIALS AND METHODS: A single-center retrospective study was performed on pleural cytology specimens from 137 patients diagnosed with a parapneumonic effusion or empyema over a five-year interval. Pleural cytology was characterized as either uncomplicated or complicated by two pathologists based on cellular composition and the presence or absence of fibrinous exudate in the fluid. Cohen's kappa was calculated for interobserver agreement. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of cytologic diagnoses were calculated. Determinants of cytologic accuracy were assessed using Wilcoxon rank sum test, unpaired t-test, and logistic regression. RESULTS: Kappa interobserver agreement between pathologists was 0.753. Pleural fluid cytology sensitivity, specificity, PPV, and NPV for CPE/empyema were 76.0%, 95% CI [65.0, 84.9]; 50%, 95% CI [29.1, 70.9]; 83.3%, 95% CI [76.7, 88.4]; and 38.7%, 95% CI [26.5, 52.5], respectively. The presence of pleural bacteria, elevated pleural LDH, and reduced pleural pH were nonsignificant determinants of cytologic accuracy. Logistic regression was significant for the presence of pleural bacteria (p = 0.03) in determining a successful cytologic diagnosis. CONCLUSION: Pleural cytology adds little value to traditional markers of distinguishing a UPE from CPE. Inflammation on pleural fluid cytology is suggestive of empyema or the presence of pleural fluid bacteria.

Effect of Renal Impairment on the Pharmacokinetics and Pharmacodynamics of Verinurad, a Selective Uric Acid Reabsorption Inhibitor.

BACKGROUND AND OBJECTIVE: Verinurad (RDEA3170) is a high-affinity, selective URAT1 transporter inhibitor in development for treating gout and asymptomatic hyperuricemia. This Phase I, single-dose study investigated the pharmacokinetics, pharmacodynamics, and safety of verinurad in adults with renal impairment and controls with normal renal function. METHODS: Males aged 18-85 years were enrolled with serum urate (sUA) 4.5-10 mg/dl and creatinine clearance 60- < 90, 30- < 60, 15- < 30, or ≥ 90 ml/min (mild, moderate, severe renal impairment and controls, respectively; n = 7/8). Verinurad 15 mg was administered orally under fasted conditions. Serial plasma/serum and urine samplings were 30 min pre-dose to 72 h post-dose. RESULTS: Compared to controls, verinurad maximum observed plasma concentration increased by 53, 73, and 128% and area under the concentration-time curve increased by 24, 148, and 130%, in subjects with mild, moderate, and severe renal impairment, respectively; renal clearance decreased by 5, 42, and 79%. Exposures of major verinurad metabolites also increased with increasing renal impairment. Verinurad decreased sUA in all groups, with greater maximal changes in control and mild renal impairment than moderate and severe impairment groups (- 38.3, - 36.9, - 20.5, - 12.6%, respectively). There were no adverse event-related withdrawals or clinically meaningful changes in laboratory values. CONCLUSION: Exposures of verinurad and metabolites increased with decreasing renal function. Consistent with the renal-dependent mechanism of action of verinurad, increasing severity of renal impairment was associated with decreased sUA lowering. Verinurad safety assessments were similar regardless of renal impairment. Continued investigation of verinurad is warranted in patients with gout and renal impairment. CLINICALTRIALS. GOV IDENTIFIER: NCT02219516.

Conservative management of vesicouterine fistula. A report of 2 cases.

BACKGROUND: Vesicouterine fistulas usually require laparotomy for repair. CASES: A vesicouterine fistula occurring after cesarean section was successfully managed hormonally. In another case it developed in association with an intrauterine device and was repaired translaparoscopically. CONCLUSION: Laparotomy may be avoidable in the management of a vesicouterine fistula.

Cavernous hemangioma of the cervix with intractable bleeding. A case report.

BACKGROUND: Cavernous hemangioma of the cervix is rare and may cause serious bleeding. CASE: A 33-year-old woman developed intractable cervical bleeding following pregnancy termination. Bleeding persisted despite curettage and suturing, and ultimately required hysterectomy. Cavernous hemangioma was confirmed histologically. CONCLUSION: This condition is a potential cause of uncontrollable cervical bleeding.

Prevention of homocysteine thiolactone induced atherogenesis in rats.

Thioretinamide was conjugated to coenzyme B12 to produce thioretinaco. Thioretinamide, thioretinaco, and coenzyme B12 were injected weekly into Rattus rattus that were also given atherogenic doses of homocysteine thiolactone. The presence or absence of lesions in aorta-intercostal artery junctions was examined. Control rats injected with homocysteine thiolactone (CON-Hcy) had 56.6 +/- 5.8% lesions when compared to 34.8 +/- 3.4% in control rats injected with saline (CON-Sal). Rats that received homocysteine thiolactone injection with thioretinamide (NHTR-Hcy), thioretinaco ((NHTR)2B12-Hcy), and coenzyme B12 (B12-Hcy) had 30.1 +/- 4.2%, 27.5 +/- 3.5%, and 22.8 +/- 3.0% lesions, respectively. These lesion rates were not different from those of rats receiving thioretinamide (NHTR-Sal), thioretinaco ((NHTR)2B12-Sal), and coenzyme B12 (B12-Sal) which were 31.3 +/- 1.8%, 29.8 +/- 3.9%, and 32.0 +/- 4.6%, respectively. In this study the percentage of intercostal artery lesions in rats receiving thioretinamide and homocysteine (NHTR-Hcy), coenzyme B12 and homocysteine (B12-Hcy), and thioretinaco and homocysteine ((NHTR)2/B12-Hcy) were significantly lower, 53.2%, 48.6%, and 40.3% respectively, compared to than that of the control group receiving homocysteine (CON-Hcy). Thioretinaco, thioretinamide, and coenzyme B12 provided protective effects against the atherogen homocysteine thiolactone. A new method for the synthesis of the N-substituted derivative of homocysteine thiolactone, thioretinamide, was also reported.