Pneumoperitoneum Secondary to Necrotic Intra-abdominal Lymph Node.

Pneumoperitoneum is often treated as a surgical emergency as the most common etiology is perforated hollow viscus. Here, we present the case of a man in his 70s who presented to the emergency department with fever and abdominal pain. On physical exam, he was diffusely tender in the bilateral lower quadrants with guarding. Imaging demonstrated moderate volume pneumoperitoneum. On review of his imaging, the pneumoperitoneum was centered around a 7 cm necrotic lymph node. Repeat CT scan with positive oral (PO) and rectal contrast demonstrated no extraluminal contrast extravasation, but air bubbles were seen extending from the necrotic lymph node into the lower abdominal cavity. He underwent CT-guided drain placement and was started on antibiotics, and improved without surgical intervention. In stable patients presenting with pneumoperitoneum and known intra-abdominal lymphadenopathy, perforated viscus should be ruled out prior to surgical intervention, and necrotic intra-abdominal lymph node should be considered as a differential diagnosis.

Clinical outcomes for patients on antiplatelet and anticoagulants in thoracoabdominal trauma.

Introduction: Trauma outcomes can be greatly affected by antiplatelet and anticoagulant (AP/AC) use. The goal of this study was to compare outcomes in trauma patients on AP/AC undergoing emergent surgery for thoracoabdominal trauma at 35 level 1 and 2 trauma centers from 2014 to 2021. Methods: This was a retrospective cohort study of 2460 adult patients with a chest, abdomen, or pelvis abbreviated injury score (AIS) of 2 or more who underwent surgery within 24 h of admission. These patients were segregated into four main cohorts based on antiplatelet/anticoagulation use: those not on AP/AC, those taking direct-acting oral anticoagulants (DOACs), those taking clopidogrel, and those taking warfarin. Patients were excluded if they had surgery >24 h after presentation, were dead on arrival, or had any other body system AIS score of 3 or higher. Results: The mean injury severity score (ISS) in all four groups ranged from 16.3 to 18.6 (p = 0.834) with a mean time to operating room from 208 to 478 min (p < 0.001). Laparotomy was performed in 60 to 71 % (p > 0.01) of patients, regardless of AP/AC status, and thoracic procedures were performed in 3.1 to 9.3 % (p = 0.42) of patients. In-hospital mortality and hospice rates were highest in the clopidogrel group at 21.9 %, followed by warfarin at 13 %, DOACs at 15 %, and no AP/AC at 7.63 % (p = 0.008). Serious complications occurred in 61 % of patients on warfarin, 50 % of those on DOACs, and 44 % of those on clopidogrel. All of these groups demonstrated significantly higher complication rates than patients in the no AP/AC control group at 25 % (p < 0.001). Total transfusion of packed red blood cells and fresh frozen plasma did not differ significantly between the groups; however, 24-h platelet transfusion did. Patients on clopidogrel received 14 packs of platelets, while those on warfarin and DOACs received 8 and 13 packs respectively (p = 0.011). Patients on warfarin had the longest hospital length of stay (LOS) at 13 days and ICU LOS at 9 days, compared to those on DOACs (8 and 4), those on clopidogrel (7 and 3), and those not taking AC/AP (7 and 4) (hospital LOS p = 0.03, ICU LOS p = 0.019). Those on AC/AP were also noted to be significantly older than those on neither, with those taking these medications averaging out to be approximately 69 years old and those not on these medications averaging 37 years old (p < 0.001). Conclusion: There was significantly higher mortality in patients on clopidogrel and increased length of stay and risk of serious complications in patients taking DOACs and warfarin. In patients on AP/AC there was also a significantly longer time to surgery than in those not taking either. Given these associations trauma surgeons should consider intervening sooner on patients taking AP/AC on admission, as the delay to intervention may contribute to the risks for trauma patients and result in worse outcomes as well as higher rates of mortality.

Early VTE prophylaxis in severe traumatic brain injury: A propensity score weighted EAST multicenter study.

BACKGROUND: Patients with traumatic brain injury (TBI) are at high risk of venous thromboembolism events (VTE). We hypothesized that early chemical VTE prophylaxis initiation (≤24 hours of a stable head CT) in severe TBI would reduce VTE without increasing risk of intracranial hemorrhage expansion (ICHE). METHODS: A retrospective review of adult patients 18 years or older with isolated severe TBI (Abbreviated Injury Scale score, ≥ 3) who were admitted to 24 Level I and Level II trauma centers from January 1, 2014 to December 31 2020 was conducted. Patients were divided into those who did not receive any VTE prophylaxis (NO VTEP), who received VTE prophylaxis ≤24 hours after stable head CT (VTEP ≤24) and who received VTE prophylaxis >24 hours after stable head CT (VTEP>24). Primary outcomes were VTE and ICHE. Covariate balancing propensity score weighting was utilized to balance demographic and clinical characteristics across three groups. Weighted univariate logistic regression models were estimated for VTE and ICHE with patient group as predictor of interest. RESULTS: Of 3,936 patients, 1,784 met inclusion criteria. Incidences of VTE was significantly higher in the VTEP>24 group, with higher incidences of DVT in the group. Higher incidences of ICHE were observed in the VTEP≤24 and VTEP>24 groups. After propensity score weighting, there was a higher risk of VTE in patients in VTEP >24 compared with those in VTEP≤24 (odds ratio, 1.51; 95% confidence interval, 0.69-3.30; p = 0.307), however was not significant. Although, the No VTEP group had decreased odds of having ICHE compared with VTEP≤24 (odds ratio, 0.75; 95% confidence interval, 0.55-1.02, p = 0.070), the result was not statistically significant. CONCLUSION: In this large multi-center analysis, there were no significant differences in VTE based on timing of initiation of VTE prophylaxis. Patients who never received VTE prophylaxis had decreased odds of ICHE. Further evaluation of VTE prophylaxis in larger randomized studies will be necessary for definitive conclusions. LEVEL OF EVIDENCE: Therapeutic Care Management; Level III.

Effect of Antiplatelet and Anticoagulant Agents on Outcomes Following Emergent Surgery for Traumatic Brain Injuries.

PURPOSE: Traumatic brain injury (TBI) is the largest cause of death from injury in the United States. This study utilized the Michigan Trauma Quality Improvement Program (MTQIP) database to determine the effect that antiplatelets and anticoagulants (AP/AC) have on outcomes following emergent surgery for TBI patients. BASIC PROCEDURES: Patients were included with age ≥18 years, maximum head/neck abbreviated injury score (AIS) ≥2, and underwent a neurosurgical procedure within 24 hours. Patients were excluded if they had an AIS ≥3 in other body region or no signs of life at initial evaluation. MAIN FINDINGS: Within the 1,932 patients analyzed, 139 (8.74%) were in the warfarin with or without (+/-) aspirin cohort, 101 (6.35%) in the direct oral anticoagulants (DOAC) +/- aspirin cohort, 169 (10.62%) in the clopidogrel +/- aspirin cohort, and 1,182 (74.29%) in the no AP/AC cohort (control group). After controlling for demographic and clinical characteristics, no significant difference in mortality rates was observed in the treatment groups (P > 0.05). However, our subgroup analysis did reveal a significantly higher mortality rate within the warfarin and aspirin subgroup when compared to the control group (odds ratio [OR], 2.368; confidence interval [CI], 1.306-4.294, P = 0.005). With regards to hospital complications, there was a significant increase in this outcome within the DOAC +/- aspirin (OR, 1.825; CI, 1.143-2.915, P = 0.012) and clopidogrel +/- aspirin (OR, 1.82; CI, 1.244-2.663, P=0.002) groups. CONCLUSION: Patients on AP/AC who experience a TBI requiring an emergent operation do not have an increased risk of mortality compared to patients not on AP/AC.

Academic Medical Centers Experienced Higher Rates of Post-Operative Health-Care-Associated Infections during the COVID-19 Pandemic: A Post Hoc Analysis of an Eastern Association for the Surgery of Trauma Multicenter Trial.

Background: We sought to examine health-care-associated infections (HAIs) among patients undergoing an appendectomy at academic medical centers (AMCs) and non-AMCs during the coronavirus disease 2019 (COVID-19) peri-pandemic. We hypothesized that AMCs would have higher rates of post-operative HAIs during the first wave of the pandemic. Patients and Methods: We performed a post hoc analysis of a prospective, observational, multi-center study of patients aged >18 years who underwent an appendectomy for acute appendicitis before (pre-CoV), during (CoV), and after pandemic restrictions were lifted (post-CoV). Patients were grouped according to hospital type (AMC vs. non-AMC). Our primary outcome was the incidence of post-operative HAIs. Results: There were 1,003 patients; 69.5% (n = 697) were treated at AMCs and 30.5% (n = 306) at non-AMCs. Patients at AMCs had greater rates of concomitant COVID-19 infections (5.5% vs. 0.7%; p < 0.0001) and worse operative appendicitis severity (p = 0.01). Greater rates of HAIs were seen at AMCs compared with non-AMCs (4.9% vs. 2%; p = 0.03). Surgical site infections were the most common HAI and occurred more often at AMCs (4.3% vs. 1.6%; p = 0.04). Only during CoV were there more HAIs at AMCs (5.1% vs. 0.3%; p = 0.02). Undergoing surgery at an AMC during CoV was a risk factor for HAIs (adjusted odds ratio [aOR], 8.55; 95% confidence interval [CI], 1.03-71.03; p = 0.04). Conclusions: During the COVID-19 pandemic, appendectomies performed at AMCs were an independent risk factor for post-operative HAIs. Our findings stress the importance of adherence to standard infection prevention efforts during future healthcare crises.

Case report: A rare presentation of high risk epithelioid hemangioendothelioma on leg treated with surgical excision.

INTRODUCTION: A rare vascular tumor, epithelioid hemangioendothelioma (EHE), can be difficult to diagnose for physicians. Although uncommon, EHE has the potential to become malignant and cause patient death. The five year mortality rate with the diagnosis of the high risk type has been reported to be as high as 41. Thus this finding requires aggressive treatment to prevent amputation or death (Deyrup et al., 2008). PRESENTATION OF CASE: In this case, a 60-year-old male patient was evaluated for a suspicious subepidermal nodule on the upper lateral aspect of the lower right leg just distal to the knee. It was excised to the level of muscle with appropriate margins of 1 cm circumferentially. The specimen underwent appropriate pathological testing and did reveal a high-risk-type epithelioid hemangioendothelioma with remaining tumor present at the deep margin. The patient had additional surgery by an orthopedic surgeon in order to obtain clear margins of the lesion and retain maximum function of leg. Despite surgical excision with ultimately clean margins, the lesion did metastasize to the right groin area seven months after surgery and the secondary metastatic site also required surgical excision. DISCUSSION: There is very little information available to the identification and treatment of a finding of EHE. The only definitive treatments to prevent malignancy is excision or amputation, possibly in conjunction with radiation therapy. The role of oncology intervention should be considered because the finding may be either a cause or an effect of malignancy. CONCLUSION: The goal of this paper is to raise awareness of the importance of pathology for soft issue lesions even if there is initially a low clinical index of suspicion. Unique characteristics in the pathology is the cornerstone to the identification and treatment. Although surgical excision can appear to be a curative treatment, EHE may inevitably metastasize, so aggressive and definitive treatment is best.

Biliary hyperkinesia, a new diagnosis or misunderstood pathophysiology of dyskinesia: A case report.

INTRODUCTION: Biliary colic, characterized by intermittent right upper quadrant abdominal pain is a common complaint in the United States population. Patients whose pain is undiagnosed by ultrasound generally undergo hepatobiliary iminodiacetic acid scan with cholecystokinin stimulation (HIDA-CCK) to assess function of the gallbladder and biliary tree. Traditionally, two outcomes are possible based on a measured ejection fraction of the gallbladder: either dyskinesia or normal function is diagnosed. Biliary dyskinesia, or hypokinesia of the gallbladder, is accepted as an ejection fraction less than 35%, while an accepted normal functioning gallbladder ejection fraction is greater than 35%. CASE: We report a case of a fifteen-year-old female who had functional gallbladder disease per Rome IV criteria due to intermittent biliary colic, with exception to the ejection fraction measurement which was elevated at 96.5%. She underwent laparoscopic cholecystectomy with complete symptom resolution. DISCUSSION: As demonstrated in the literature reviewed here, these subsets of patients, who present with normal to high ejection fractions, have undergone laparoscopic cholecystectomy with resolution of pain in several case studies. CONCLUSION: Many unknown variables still exist due to lack of prospective studies, most notably the pathophysiology and definitive indications for surgical treatment. As such, we propose that surgical options should not be limited to those who display the traditional findings of biliary dyskinesia, but also patients who demonstrate typical symptoms with normal to elevated ejection fraction, following work up to rule out the extensive differential diagnoses for right upper quadrant abdominal pain.

After the embo: predicting non-hemorrhagic indications for splenectomy after angioembolization in patients with blunt trauma.

BACKGROUND: Successful non-operative management (NOM) of blunt splenic trauma is enhanced with splenic angioembolization (SAE). Patients may still require splenectomy post-SAE for splenic infarction/necrosis. Prior studies have used white blood cell count (WBC), platelet count (PLT), and PLT:WBC ratio after splenectomy to predict complications, but none have evaluated these findings prior to splenectomy in patients who have undergone SAE. Changes in these values may indicate clinically significant splenic infarction, facilitating management of these patients. METHODS: Patients admitted to an American College of Surgeons verified level 1 trauma center from January 2007 to August 2017 who underwent SAE were identified. Patients with successful NOM after SAE (SAE/NOM) were compared with those requiring splenectomy (SAE/SPLEN). Data included demographics, splenic injury grade, Injury Severity Score (ISS), time to SAE and splenectomy, intensive care unit and hospital length of stay (LOS), and complete blood count. Lab values were analyzed immediately post-SAE (time 1) and day 5 post-SAE (or day of discharge) for SAE/NOM patients and day of SPLEN for SAE/SPLEN patients (time 2). Data were analyzed using Mann-Whitney U, χ2 tests, and receiver operating characteristic (ROC) curves with significance attributed to P<0.05. RESULTS: Of 124 patients undergoing SAE, 16 (13%) later required SPLEN for infarction/necrosis at a median of 5 days post-SAE (IQR: 3-10 days). SAE/SPLEN and SAE/NOM patients did not differ by age, gender, ISS, or grade of splenic injury. SAE/SPLEN patients had longer hospital LOS (23 vs. 10 days, P<0.001). WBC, PLT, and PLT:WBC ratio did not differ between the groups at time 1. At time 2, WBC was higher and PLT:WBC ratio was lower in SAE/SPLEN patients. Using ROC curves at time 2, the area under the curve was 0.90 (P<0.001) for WBC and 0.71 (P<0.007) for PLT:WBC ratio. DISCUSSION: Patients requiring splenectomy for clinically significant infarction/necrosis after SAE develop leukocytosis and decreased PLT:WBC ratio when compared with SAE/NOM patients. Monitoring these parameters allows more prompt diagnosis and operative intervention. LEVEL OF EVIDENCE: Therapeutic/care management, level III.

Glial Cells Missing 1 Regulates Equine Chorionic Gonadotrophin Beta Subunit via Binding to the Proximal Promoter.

Equine chorionic gonadotrophin (eCG) is a placental glycoprotein critical for early equine pregnancy and used therapeutically in a number of species to support reproductive activity. The factors in trophoblast that transcriptionally regulate eCGß-subunit (LHB), the gene which confers the hormones specificity for the receptor, are not known. The aim of this study was to determine if glial cells missing 1 regulates LHB promoter activity. Here, studies of the LHB proximal promoter identified four binding sites for glial cells missing 1 (GCM1) and western blot analysis confirmed GCM1 was expressed in equine chorionic girdle (ChG) and surrounding tissues. Luciferase assays demonstrated endogenous activity of the LHB promoter in BeWo choriocarcinoma cells with greatest activity by a proximal 335 bp promoter fragment. Transactivation studies in COS7 cells using an equine GCM1 expression vector showed GCM1 could transactivate the proximal 335 bp LHB promoter. Chromatin immunoprecipitation using primary ChG trophoblast cells showed GCM1 to preferentially bind to the most proximal GCM1-binding site over site 2. Mutation of site 1 but not site 2 resulted in a loss of endogenous promoter activity in BeWo cells and failure of GCM1 to transactivate the promoter in COS-7 cells. Together, these data show that GCM1 binds to site 1 in the LHB promoter but also requires the upstream segment of the LHB promoter between -119 bp and -335 bp of the translation start codon for activity. GCM1 binding partners, ETV1, ETV7, HOXA13, and PITX1, were found to be differentially expressed in the ChG between days 27 and 34 and are excellent candidates for this role. In conclusion, GCM1 was demonstrated to drive the LHB promoter, through direct binding to a predicted GCM1-binding site, with requirement for another factor(s) to bind the proximal promoter to exert this function. Based on these findings, we hypothesize that ETV7 and HOXA13 act in concert with GCM1 to initiate LHB transcription between days 30 and 31, with ETV1 partnering with GCM1 to maintain transcription.

Convergent evolution of pregnancy-specific glycoproteins in human and horse.

Pregnancy-specific glycoproteins (PSGs) are members of the carcinoembryonic antigen cell adhesion molecule (CEACAM) family that are secreted by trophoblast cells. PSGs may modulate immune, angiogenic and platelet responses during pregnancy. Until now, PSGs are only found in species that have a highly invasive (hemochorial) placentation including humans, mice and rats. Surprisingly, analyzing the CEACAM gene family of the horse, which has a non-invasive epitheliochorial placenta, with the exception of the transient endometrial cups, we identified equine CEACAM family members that seem to be related to PSGs of rodents and primates. We identified seven genes that encode secreted PSG-like CEACAMs Phylogenetic analyses indicate that they evolved independently from an equine CEACAM1-like ancestor rather than from a common PSG-like ancestor with rodents and primates. Significantly, expression of PSG-like genes (CEACAM44, CEACAM48, CEACAM49 and CEACAM55) was found in non-invasive as well as invasive trophoblast cells such as purified chorionic girdle cells and endometrial cup cells. Chorionic girdle cells are highly invasive trophoblast cells that invade the endometrium of the mare where they form endometrial cups and are in close contact with maternal immune cells. Therefore, the microenvironment of invasive equine trophoblast cells has striking similarities to the microenvironment of trophoblast cells in hemochorial placentas, suggesting that equine PSG-like CEACAMs and rodent and primate PSGs have undergone convergent evolution. This is supported by our finding that equine PSG-like CEACAM49 exhibits similar activity to certain rodent and human PSGs in a functional assay of platelet-fibrinogen binding. Our results have implications for understanding the evolution of PSGs and their functions in maternal-fetal interactions.

Urinalysis: case presentations for the primary care physician.

Urinalysis is useful in diagnosing systemic and genitourinary conditions. In patients with suspected microscopic hematuria, urine dipstick testing may suggest the presence of blood, but results should be confirmed with a microscopic examination. In the absence of obvious causes, the evaluation of microscopic hematuria should include renal function testing, urinary tract imaging, and cystoscopy. In a patient with a ureteral stent, urinalysis alone cannot establish the diagnosis of urinary tract infection. Plain radiography of the kidneys, ureters, and bladder can identify a stent and is preferred over computed tomography. Asymptomatic bacteriuria is the isolation of bacteria in an appropriately collected urine specimen obtained from a person without symptoms of a urinary tract infection. Treatment of asymptomatic bacteriuria is not recommended in nonpregnant adults, including those with prolonged urinary catheter use.

Assessment of asymptomatic microscopic hematuria in adults.

Although routine screening for bladder cancer is not recommended, microscopic hematuria is often incidentally discovered by primary care physicians. The American Urological Association has published an updated guideline for the management of asymptomatic microscopic hematuria, which is defined as the presence of three or more red blood cells per high-power field visible in a properly collected urine specimen without evidence of infection. The most common causes of microscopic hematuria are urinary tract infection, benign prostatic hyperplasia, and urinary calculi. However, up to 5% of patients with asymptomatic microscopic hematuria are found to have a urinary tract malignancy. The risk of urologic malignancy is increased in men, persons older than 35 years, and persons with a history of smoking. Microscopic hematuria in the setting of urinary tract infection should resolve after appropriate antibiotic treatment; persistence of hematuria warrants a diagnostic workup. Dysmorphic red blood cells, cellular casts, proteinuria, elevated creatinine levels, or hypertension in the presence of microscopic hematuria should prompt concurrent nephrologic and urologic referral. The upper urinary tract is best evaluated with multiphasic computed tomography urography, which identifies hydronephrosis, urinary calculi, and renal and ureteral lesions. The lower urinary tract is best evaluated with cystoscopy for urethral stricture disease, benign prostatic hyperplasia, and bladder masses. Voided urine cytology is no longer recommended as part of the routine evaluation of asymptomatic microscopic hematuria, unless there are risk factors for malignancy.

Testicular torsion: diagnosis, evaluation, and management.

Testicular torsion is a twisting of the spermatic cord and its contents and is a surgical emergency affecting 3.8 per 100,000 males younger than 18 years annually. It accounts for 10% to 15% of acute scrotal disease in children, and results in an orchiectomy rate of 42% in boys undergoing surgery for testicular torsion. Prompt recognition and treatment are necessary for testicular salvage, and torsion must be excluded in all patients who present with acute scrotum. Testicular torsion is a clinical diagnosis, and patients typically present with severe acute unilateral scrotal pain, nausea, and vomiting. Physical examination may reveal a high-riding testicle with an absent cremasteric reflex. If history and physical examination suggest torsion, immediate surgical exploration is indicated and should not be postponed to perform imaging studies. There is typically a four- to eight-hour window before permanent ischemic damage occurs. Delay in treatment may be associated with decreased fertility, or may necessitate orchiectomy.

Regulation of glucocorticoid metabolism in the boar testis and caput epididymidis by the gonadotrophin-cAMP signalling pathway.

In target tissues, cortisol is metabolised by two 11ß-hydroxysteroid dehydrogenase (11ßHSD) isoenzymes, namely 11ßHSD1 and 11ßHSD2, both of which are co-expressed in the boar testis and reproductive tract. The present study has assessed whether cortisol-cortisone metabolism in boar testis and caput epididymidis can be regulated via the gonadotrophin-cAMP signalling pathway. 11ßHSD activities were measured by using a radiometric conversion assay in static tissue culture. In both testis and caput epididymidis, the net reduction of cortisone but not the net oxidation of cortisol, was significantly decreased by luteinising hormone (by 53 ± 20% and 45 ± 9%, respectively, P < 0.05), forskolin (by 60 ± 7% and 57 ± 9%, respectively, P < 0.01) and 8-bromo-cAMP (by 54 ± 4% and 64 ± 1%, respectively, P < 0.01). This suppression of 11-ketosteroid reductase activity in the boar testis by forskolin could be attenuated by the protein kinase A (PKA) inhibitor, H89. Hence, within the boar testis and the caput epididymidis, the local actions of glucocorticoids are modulated by gonadotrophin-cAMP-PKA signalling via their selective effects on the reductase activity of 11ßHSD.

A novel treatment strategy for ovarian cancer based on immunization against zona pellucida protein (ZP) 3.

We tested the principle of treating malignant ovarian tumors by vaccination against their ectopically expressed protein, zona pellucida glycoprotein (ZP) 3, using as the experimental model the granulosa cell tumors that develop in transgenic mice expressing the simian virus 40 T-antigen under the inhibin-α promoter (inhα/Tag). We found high ZP3 expression in granulosa cell tumors of the transgenic mice, in human surface ovarian cancer and granulosa cell lines, and in human granulosa cell tumors and their metastases. Early preventive immunization (between 2 and 5.5 mo of age) of transgenic mice with recombinant human (rh) ZP3 prevented ovarian tumorigenesis, and delayed therapeutic immunization (between 4.5 and 7 mo) reduced weights of existing tumors by 86 and 75%, respectively (P<0.001), compared to vehicle-treated control mice. No objective side effects of the immunizations were observed. Liver metastases were found in nontreated/vehicle-treated controls (n=7/39), but none following active rhZP3 immunizations (n=0/36; P<0.05). Immunization with rhZP3 was highly effective, as demonstrated by the induction of anti-ZP3 antibodies, as well as proliferative responses to the ZP3 antigen. These results signal rhZP3 immunization as a novel strategy to be developed for the immunotherapy of ovarian granulosa cell tumors, as well as for that of other malignancies that may express ZP3.

Epstein-Barr virus myelitis and Castleman's disease in a patient with acquired immune deficiency syndrome: a case report.

INTRODUCTION: Few cases of Epstein-Barr virus myelitis have been described in the literature. Multi-centric Castleman's disease is a lymphoproliferative disorder that is well known for its associations with the human immunodeficiency virus, human herpes virus 8, and Kaposi's sarcoma. The concurrent presentation of these two diseases in a patient at the same time is extremely unusual. CASE PRESENTATION: We describe the case of a 43-year-old Caucasian man with acquired immune deficiency syndrome who presented with fever, weight loss and diffuse lymphadenopathy, and was diagnosed with multi-centric Castleman's disease. He presented three weeks later with lower extremity weakness and urinary retention, at which time cerebrospinal fluid contained lymphocytic pleocytosis and elevated protein. Magnetic resonance imaging demonstrated abnormal spinal cord signal intensity over several cervical and thoracic segments, suggesting the diagnosis of myelitis. Our patient was ultimately diagnosed with Epstein-Barr virus myelitis, as Epstein-Barr virus DNA was detected by polymerase chain reaction in the cerebrospinal fluid. CONCLUSION: To the best of our knowledge, this is the first case of multi-centric Castleman's disease followed by acute Epstein-Barr virus myelitis in a human immunodeficiency virus-infected patient. Clinicians caring for human immunodeficiency virus-infected patients should be vigilant about monitoring patients with increasing lymphadenopathy, prompting thorough diagnostic investigations when necessary.

The relationship between lower urinary tract symptom severity and sleep disturbance in the CAMUS trial.

PURPOSE: Bothersome lower urinary tract symptoms, including nocturia, significantly impact general health related quality of life in men, as does sleep disturbance. However, few groups have examined the relationship between urinary symptom severity and sleep disturbance. MATERIALS AND METHODS: Men enrolled in a clinical trial of saw palmetto (Serenoa repens) were studied at baseline. Lower urinary tract symptom severity, as determined by the American Urological Association symptom index and quality of life scores, and the degree of sleep disturbance were determined by the Jenkins sleep scale. Analysis was done, adjusting for baseline characteristics, to identify predictors of severe sleep disturbance. RESULTS: A total of 366 men with a mean ± SD age of 60.9 ± 8.3 years who had moderate-severe lower urinary tract symptoms (mean American Urological Association symptom index score 14.58 ± 4.6 points) and a mean Jenkins sleep score of 7.3 ± 4.7 points were included in analysis. Overall there were significant associations between the American Urological Association symptom index score and sleep disturbance severity. Multivariate analysis revealed that obstructive and irritative symptoms were significantly associated with severe sleep disturbance. Further analysis showed that lower serum prostate specific antigen and post-void residual urine volume were also significantly associated with the degree of sleep disturbance. CONCLUSIONS: Lower urinary tract symptom severity is a risk factor for severe sleep disturbance in men. While nocturia was significantly associated with sleep disturbance, other lower urinary tract symptoms were also independent predictors of sleep dysfunction.

Targeted inactivation of the androgen receptor gene in murine proximal epididymis causes epithelial hypotrophy and obstructive azoospermia.

The epithelial lining of the epididymal duct expresses the androgen receptor (Ar) along its entire length and undergoes rapid and profound degeneration when androgenic support is withdrawn. However, experiments involving orchidectomy with systemic testosterone replacement, and testicular efferent duct ligation, have indicated that structural and functional integrity of the initial segment cannot be maintained by circulating androgen alone, leaving the role of androgen in this epididymal zone unclear. We addressed this question in a mouse model with intact testicular output and selective Ar inactivation in the proximal epididymis by creating double-transgenic males carrying a conditional Ar(loxP) allele and expressing Cre recombinase under the promoter of Rnase10, a gene specifically expressed in proximal epididymis. At 20-25 d of life, on the onset of Rnase10 expression, Ar became selectively inactivated in the principal cells of proximal epididymis, resulting in epithelial hypoplasia and hypotrophy. Upon the subsequent onset of spermiation, epididymal obstruction ensued, with the consequent development of spermatic granulomata, back pressure-induced atrophy of the seminiferous epithelium, orchitis, and fibrosis of the testicular parenchyma. Consistent with these findings, the mice were infertile. When the effect of Ar knockout on gene expression in the proximal epididymis was compared with that of efferent duct ligation and orchidectomy, we identified genes specifically regulated by androgen, testicular efferent fluid, and both. Our findings demonstrate that the development and function of the epididymal initial segment is critically dependent on direct androgen regulation. The phenotype of the produced knockout mouse provides a novel model for obstructive azoospermia.