Dural sinus narrowing in patients with spontaneous anterior skull base cerebrospinal fluid leak.

Objectives: Current evidence suggests a link between idiopathic intracranial hypertension (IIH) and spontaneous cerebrospinal fluid (sCSF) leak, as well as between IIH and dural venous sinus (DVS) narrowing. However, there are limited data linking DVS narrowing and sCSF leak. This study aims to determine the prevalence of DVS narrowing in patients with sCSF leak. Methods: A retrospective review of all patients with sCSF leak that presented to a tertiary academic center from 2008 to 2019. Preoperative imaging was independently reviewed by two neuroradiologists to evaluate for DVS narrowing. Available literature was used to estimate the prevalence of DVS narrowing in the general population to allow for comparison. Data were analyzed using Exact binomial test. Results: Analysis of 25 patients with appropriate imaging revealed the majority were women (21/25, 84%) with a mean age of 51.89 years (SD 13.96). The majority of these patients were found to have narrowing of the DVS (20/25, 80%). In patient with sCSF leaks, there was a significantly higher proportion of patients with DVS narrowing compared with published literature examining this condition in the general population (80% vs. 40%, CI 0.59-0.93, p < .001). Conclusion: The prevalence of DVS narrowing in patients with sCSF leaks is substantial and likely greater than the general population. Moreover, there appears to be narrowing in most patients with sCSF leak. Preoperative radiological evaluation of the DVS using MR venography may be useful in patients with sCSF leaks as DVS stenosis may be an underdiagnosed etiology. Further study is needed to evaluate this. Level of Evidence: IV.

Mosaic Bovine Viral Diarrhea Virus Antigens Elicit Cross-Protective Immunity in Calves.

Bovine Viral Diarrhea Virus (BVDV) is an important pathogen that plays a significant role in initiating Bovine Respiratory Disease Complex (BRDC) in cattle. The disease causes multi-billion dollar losses globally due to high calf mortality and increased morbidity leading to heavy use of antibiotics. Current commercial vaccines provide limited cross-protection with several drawbacks such as safety, immunosuppression, potential reversion to virulence, and induction of neonatal pancytopenia. This study evaluates two prototype vaccines containing multiple rationally designed recombinant mosaic BVDV antigens for their potential to confer cross-protection against diverse BVDV strains. Genes encoding three novel mosaic antigens, designated E2123, NS2-31, and NS2-32, were designed in silico and expressed in mammalian cells for the formulation of a prototype protein-based vaccine. The mosaic antigens contain highly conserved protective epitopes from BVDV-1a, -1b, and -2, and included unique neutralizing epitopes from disparate strains to broaden coverage. We tested immunogenicity and protective efficacy of Expi293TM-expressed mosaic antigens (293F-E2123, 293F-NS2-31, and 293F-NS2-32), and baculovirus-expressed E2123 (Bac-E2123) mosaic antigen in calves. The Expi293TM-expressed antigen cocktail induced robust BVDV-specific cross-reactive IFN-γ responses, broadly neutralizing antibodies, and following challenge with a BVDV-1b strain, the calves had significantly (p < 0.05) reduced viremia and clinical BVD disease compared to the calves vaccinated with a commercial killed vaccine. The Bac-E2123 antigen was not as effective as the Expi293TM-expressed antigen cocktail, but it protected calves from BVD disease better than the commercial killed vaccine. The findings support feasibility for development of a broadly protective subunit BVDV vaccine for safe and effective management of BRD.

4D-CT facilitates focused parathyroidectomy in patients with primary hyperparathyroidism by maintaining a high negative-predictive value for uninvolved quadrants.

INTRODUCTION: Improved preoperative localization facilitates minimally invasive parathyroidectomy for removal of parathyroid lesions therefore preventing an invasive bilateral neck exploration. As 4D-CT has emerged, its high specificity has helped with preoperative parathyroid lesion localization. A high negative predictive value (NPV) would serve to further confirm parathyroid lesion localization and limit unnecessary surgical exploration. This study's objective was to determine the NPV of preoperative 4D-CT and its facilitation of minimally invasive parathyroidectomy. METHODS: A retrospective review was compiled for patients undergoing parathyroidectomy for primary hyperparathyroidism with a preoperative 4D-CT. Included patients were sorted into various groups for comparison: those with 4D-CT localizing to a single lesion, localizing to multiple lesions, and those with nonlocalizing findings; multiple hypercellular parathyroid gland versus single gland findings; extent of surgical exploration; lesion location; and patients with concomitant thyroid nodules. Negative predictive value was calculated and used to quantify the ability for 4D-CT to rule out biochemically significant parathyroid lesions. RESULTS: In our review of 68 patients: sensitivity was 81.3%, specificity was 95.5%, positive predictive value was 87.1%, and negative predictive value was 93.3%. 86% had a single localizing 4D-CT, 7% had a non-localizing 4D-CT, and 7% had a multiple quadrant localizing 4D-CT. NPV for single and multi-localizing 4D-CT were 96.8% and 88.9%, respectively. CONCLUSION: Preoperative 4D-CT has a high negative predictive value (93.3%), suggesting in the majority of cases, a quadrant with no 4D-CT radiographic findings suspicious for parathyroid is unlikely to harbor biochemically significant parathyroid lesions.

Evaluation of essential oils and a prebiotic for newborn dairy calves.

A blend of essential oils (EO) and a prebiotic were combined (EOC) to formulate a colostrum-based liquid birth supplement and a separate feeding supplement (Start Strong and Stay Strong, Ralco Inc., Marshall, MN). These products were designed to promote immunity and stimulate appetite to diminish health challenges and stresses experienced by newborn calves. The hypothesis was that calves supplemented with an oral dose of liquid EOC at birth (10-mL aliquot at birth and 10 mL at 12 h of age) when fed the EOC feeding supplement would result in improved growth performance, health, and immunity. The objective was to determine if an additional feeding of liquid EOC at birth in combination with EOC in the milk replacer (MR) would allow calves to demonstrate improved growth, health, and immunity compare with calves only offered EO in MR. Sixty-one Holstein calves (18 males and 43 females) from a commercial dairy operation were blocked by birth date and randomly assigned to 1 of 3 treatments. Treatments were 1) Control (CON): a 24% crude protein (CP):20% fat (as-fed basis) MR; 2) EP: a 24:20 MR with EOC mixed at 1.25 g/d; or 3) EPC: a 24:20 MR with EOC mixed at 1.25 g/d in addition to calves receiving one 10-mL oral dose of liquid EOC at birth and 10 mL again at 12 h. The 24:20 MR was fed via bucket 2 times per day at a rate of 0.57 kg/calf daily for 14 d, increased to 0.85 kg/calf at 2 times per day until 35 d and was reduced to 0.43 kg at 1 time per day at 36 d to facilitate weaning after 42 d. Decoquinate was added to the MR at 41.6 mg/kg for coccidiosis control. Calves were housed in individual hutches bedded with straw with ad libitum access to a 20% CP-pelleted calf starter and water. All data were analyzed using PROC MIXED as a randomized complete block design. Calves in this study had similar (P > 0.10) average daily gains, body weight, and growth measurements. Calves fed EPC had significantly (P < 0.05) higher IgA titers on day 0 of the trial compared with calves fed EP or CON, which was expected as calves were supplemented with liquid EOC at birth and 12 h later demonstrating an increase in immune response. The use of a liquid EOC product being administrated after birth can improve IgA titers to improve the immune status of the new born calf to fight off potential diseases and pathogens. A formulation error resulted in the EOC being fed at half the rate of the previous experiment of 2.5 g/d, which appears to be below an efficacious dosage.

Protection against bovine respiratory syncytial virus in calves vaccinated with adjuvanted modified live vaccine administered in the face of maternal antibody.

Bovine respiratory syncytial virus (BRSV) is major viral contributor to bovine respiratory disease (BRD). BRD is a major cause of morbidity and mortality in all classes of cattle but particularly young beef and dairy calves. Passive antibodies not only help protect the calf against infection, but may interfere with the immune responses following vaccination. The purpose of this study was to evaluate the efficacy of an adjuvanted modified live virus (MLV) vaccine in the presence of well-defined maternal passive immunity. Calves were vaccinated at approximately 1 month of age and challenged ~90 days later when BRSV systemic antibodies were ≤1:4. Body temperature was lower at 6 and 7 days post challenge and other clinical signs were also lower in the vaccinates. Nasal viral shed was 3-4 times lower in the vaccinated animals as measured by virus isolation and polymerase chain reaction (PCR) and peaked 5 days post challenge compared to the controls (who peaked at days 6 and 7). On day 8 following challenge, animals were necropsied, and lung lobes were scored and tested for virus by PCR and indirect fluorescent assay (IFA). There was a 25-fold reduction in PCR virus detection in vaccinates and two of the vaccinated calves' lungs were PCR negative. Only 29.4% of vaccinated calves were BRSV positive on IFA testing at necropsy, while 87.5% of control calves were BRSV positive. Vaccinated calves developed a mucosal BRSV IgA response with over 50% of the vaccinated calves having IgA prior to challenge and all vaccinated calves were positive following challenge. Additionally, vaccination stimulated the production of Interferon gamma (IFN-γ) in mononuclear cells to prime the immune system. This study established that an adjuvanted MLV vaccine could provide protection against BRSV as measured by clinical, virological, and pathological parameters while also activating both mucosal and systemic immunity.

Massive aneurysmal bone cyst of the skull base treated with denosumab.

BACKGROUND: Aneurysmal bone cysts are rare, benign expansile tumors most commonly involving long bones and vertebrae in patients younger than age 20. Skull base involvement is rare. Aneurysmal bone cysts shares radiological and histological features with other bone tumors, posing a diagnostic challenge. METHODS/RESULTS: We report the case of a 32-year-old man who presented with facial pain, epistaxis, and cranial neuropathies secondary to a massive tumor of the maxillary sinus and anterior skull base. The tumor was originally misdiagnosed as osteosarcoma. However, genomic analysis revealed a rearrangement in the USP6 gene, elucidating a diagnosis of primary aneurysmal bone cysts. The patient was treated with denosumab. Within 5 months, the patient was asymptomatic with CT showing ossification of the tumor. CONCLUSIONS: This case highlights (1) the utility of genomic analysis in aggressive bone tumors when the diagnosis is unclear and (2) the effectiveness of denosumab as a treatment for aneurysmal bone cysts when surgical resection is unfavorable.

Osseointegrated Transcutaneous Device for Amputees: A Pilot Large Animal Model.

Traditional above-the-knee amputation prosthetics utilize a stump-socket interface that is well-known for skin/socket problems, sitting difficulty, disuse osteopenia, and increased work of ambulation. As a result, we evaluated a novel osseointegrated transcutaneous implant in a large animal. The implant was designed to promote osseointegration at the bone-implant interface and minimize complications. As proof of concept, four Dorset sheep underwent a two-stage surgery for forelimb placement of an osseointegrated transcutaneous implant utilizing Compress® technology (Biomet, Inc., Warsaw, IN). Two sheep received a long anchor plug (90 mm long x 9 mm in diameter) and two received a short anchor plug (46 mm long x 9 mm in diameter). Sixteen weeks after the initial surgery, the operative limbs, along with the attached implant, underwent radiographic and histological analysis for osseointegration. Periprosthetic fractures occurred in the two animals that received the longer internal prosthesis; one healed with splinting and the other animal underwent a second surgical procedure to advance the amputation site more proximal. No fractures occurred in the shorter internal prosthesis group. There was no histological evidence of infection and none of the transcutaneous adapters failed. Bone-implant osseointegration was demonstrated in two of three limbs that underwent histological analysis. This unique implant demonstrated osseointegration without transcutaneous adapter failure, all while displaying minimal infection risk from the outside environment. Although it involved short-term follow-up in a limited number of animals, this pilot study provides a platform for further investigation into the valid concept of using Compress® technology as an endo-exo device.

Clostridium difficile-Associated Colitis Post-Transplant Is Not Associated with Elevation of Tacrolimus Concentrations.

BACKGROUND: Diarrhea is a common condition after solid organ transplant (SOT); Clostridium difficile-associated colitis (CDAC) is one of the most common infections after SOT. We documented previously that some types of enteritis are associated with an elevation of tacrolimus (TAC) trough concentrations by interfering with the drug's complex metabolism. PATIENTS AND METHODS: Tacrolimus concentrations of 25 SOT recipients including 12 renal and 13 liver recipients before, during, and after CDAC were analyzed retrospectively. RESULTS: Median age of the 25 patients was 54 y (range, 36-71), there were 15 males and 10 females. Clostridium difficile-associated colitis developed at a median of 55 d (range 2-4551) post-SOT. Median TAC concentrations prior to the outbreak of CDAC were 6.9 ng/mL (range, <1.5-17.2), 5.6 ng/mL (range, <1.5-13.2) during diarrhea, and 7.4 ng/mL (range, <1.5-24.3) after resolution of diarrhea (p > 0.05, NS). Treatment of CDAC consisted of metronidazole for 14 d in all cases. All patients recovered from CDAC but seven patients had CDAC relapse. CONCLUSIONS: In contrast to other types of infectious diarrhea such as rotavirus enteritis and cryptosporidiosis, CDAC is not associated with an increase in TAC concentrations. This is because C. difficile causes primarily colitis as opposed to other organisms, which are associated with enteritis.

Priming Cross-Protective Bovine Viral Diarrhea Virus-Specific Immunity Using Live-Vectored Mosaic Antigens.

Bovine viral diarrhea virus (BVDV) plays a key role in bovine respiratory disease complex, which can lead to pneumonia, diarrhea and death of calves. Current vaccines are not very effective due, in part, to immunosuppressive traits and failure to induce broad protection. There are diverse BVDV strains and thus, current vaccines contain representative genotype 1 and 2 viruses (BVDV-1 & 2) to broaden coverage. BVDV modified live virus (MLV) vaccines are superior to killed virus vaccines, but they are susceptible to neutralization and complement-mediated destruction triggered by passively acquired antibodies, thus limiting their efficacy. We generated three novel mosaic polypeptide chimeras, designated NproE2123; NS231; and NS232, which incorporate protective determinants that are highly conserved among BVDV-1a, 1b, and BVDV-2 genotypes. In addition, strain-specific protective antigens from disparate BVDV strains were included to broaden coverage. We confirmed that adenovirus constructs expressing these antigens were strongly recognized by monoclonal antibodies, polyclonal sera, and IFN-γ-secreting T cells generated against diverse BVDV strains. In a proof-of-concept efficacy study, the multi-antigen proto-type vaccine induced higher, but not significantly different, IFN-γ spot forming cells and T-cell proliferation compared to a commercial MLV vaccine. In regards to the humoral response, the prototype vaccine induced higher BVDV-1 specific neutralizing antibody titers, whereas the MLV vaccine induced higher BVDV-2 specific neutralizing antibody titers. Following BVDV type 2a (1373) challenge, calves immunized with the proto-type or the MLV vaccine had lower clinical scores compared to naïve controls. These results support the hypothesis that a broadly protective subunit vaccine can be generated using mosaic polypeptides that incorporate rationally selected and validated protective determinants from diverse BVDV strains. Furthermore, regarding biosafety of using a live vector in cattle, we showed that recombinant human adenovirus-5 was cleared within one week following intradermal inoculation.

Bone Mineral Density and Vitamin D Level Compared to Lifestyle in Resident Physicians.

Due to the demands of resident education and long periods of time spent indoors, resident physicians may have poorer bone quality than would be expected. Forty-four resident physicians underwent dual-energy X-ray absorptiometry (DEXA) and 25-hydroxyvitamin D level testing at our institution. Results were correlated with a survey of self-reported duty hours, physical activity, and sun exposure. The average 25-hydroxyvitamin D level for all participants was 29 ng/dL, which fell into the insufficient range, and 31.5% of all participants were in the deficient range, with a 25-hydroxyvitamin D level < 20 ng/ dL. For the 40 subjects who underwent DEXA, 17 were found to be osteopenic and three were found to be osteoporotic. Greater awareness of bone health, with routine use of vitamin D supplementation and increased time spent outdoors during peak sunlight hours, may be indicated in this cohort.

Closure of ascites leaks with fibrin glue injection in patients with end-stage liver disease.

BACKGROUND: Ascites leaks (AL) in patients with end-stage liver disease (ESLD) are associated with significant morbidity and mortality regardless if they are medically or surgically managed. PATIENTS AND METHODS: In a pilot study, 14 ESLD patients with AL underwent treatment with fibrin glue injection around the leak after failing conservative therapy. The end point of this study was the cessation of AL in the short term and the maintenance of a leak-free abdomen in the long term, allowing for medical optimization of the patients. RESULTS: Median age of the 10 men and 4 women was 50 (range 26-67) years. Underlying ESLDs were chronic hepatitis C (n=5), alcoholic LD (n=2), cryptogenic cirrhosis (n=2), and miscellaneous (n=5). There were six leaking incisions posthernia repair (three umbilical and three inguinal), two leaking/ruptured umbilical hernias, four leaking paracentesis sites, one leaking Jackson-Pratt (JP) drain canal, and one leaking laparoscopic trocar site. Average AL volume per day was 1000 (range 400-2000) mL. All leaks were immediately resolved with a 3-5 mL fibrin glue injection. Five recurred and required a second injection (four within 24 hours). Mental status improved in 7 patients (West Haven Criteria: grade II to I [n=6], grade III to I [n=1]). Median model of end-stage liver disease scores improved from 23 (range 8-33) to 20 (range 14-26). There were no infections, bleeds, or other injection-related complications. Average follow-up for these patients was 441.6 days (range 2-852). Five patients underwent liver transplant (LT) median 15 (range 4-270) days postinjection; 2 of them died. Another 3 patients died (2 from sepsis and 1 from metastatic cancer). CONCLUSION: Fibrin glue injection for the control of AL is a simple and safe bedside procedure that quickly controls AL, allowing for patient recovery in anticipation of further care.

Minimally invasive parathyroidectomy using surgical sonography.

Minimally invasive parathyroidectomy is the procedure of choice for primary hyperparathyroidism due to parathyroid adenoma. Localization of the offending adenoma in minimally invasive parathyroidectomy (MIP) has been described in the literature aided by isotope, telescope or ultrasound guidance. We present a prospective study of two techniques based on surgeon experience. Thirty patients diagnosed with primary hyperparathyroidism at the Mater hospital in Dublin, Ireland were randomized to have a minimally invasive parathyroidectomy using surgical sonography (MIPUSS) or the conventional unilateral open procedure (OP) over a two year period. The age, sex and serum calcium/parathormone were comparable in both groups. There was no significant difference in complications between the two groups with temporary hypocalcemia occurring in 3 patients undergoing unilateral neck exploration and in 2 MIPUSS patients. There was one transient episode of recurrent laryngeal neuropraxia occurring in the OP group which resolved at 30 day follow-up. The incision size, operating time, hospital stay, and required post-operative analgesia were all markedly reduced in the MIPUSS group. In conclusion, MIPUSS is safe, effective and has advantages in terms of operating time, incision size and early discharge.

FTY720 promotes local microvascular network formation and regeneration of cranial bone defects.

The calvarial bone microenvironment contains a unique progenitor niche that should be considered for therapeutic manipulation when designing regeneration strategies. Recently, our group demonstrated that cells isolated from the dura are multipotent and exhibit expansion potential and robust mineralization on biodegradable constructs in vitro. In this study, we evaluate the effectiveness of healing critical-sized cranial bone defects by enhancing microvascular network growth and host dura progenitor trafficking to the defect space pharmacologically by delivering drugs targeted to sphingosine 1-phosphate (S1P) receptors. We demonstrate that delivery of pharmacological agonists to (S1P) receptors S1P(1) and S1P(3) significantly increase bone ingrowth, total microvessel density, and smooth muscle cell investment on nascent microvessels within the defect space. Further, in vitro proliferation and migration studies suggest that selective activation of S1P(3) promotes recruitment and growth of osteoblastic progenitors from the meningeal dura mater.

A case of concomitant pneumothorax and pneumoperitoneum.

Pneumothorax associated with pneumoperitoneum is rare. There are scattered case reports of this syndrome in the pediatric literature but very few reports in the adult literature. Several possible causes exist. Maurer at al. suggested that it results from air entering the pleural space through a diaphragmatic defect. In this paper, we report a patient with a perforated diverticulum and a concomitant pneumothorax.

Comparative effects of scaffold pore size, pore volume, and total void volume on cranial bone healing patterns using microsphere-based scaffolds.

Bony craniofacial deficits resulting from injury, disease, or birth defects remain a considerable clinical challenge. In this study, microsphere-based scaffold fabrication methods were use to study the respective effects of scaffold pore size, open pore volume, and total void volume fraction on osseous tissue infiltration and bone regeneration in a critical size rat cranial defect. To compare the healing effects of these parameters, three different scaffolds types were fabricated: solid 100 microm spheres, solid 500 microm spheres, and hollow 500 microm spheres. These constructs were implanted into surgically created rat calvarial defects. By 90-days post op, results of micro computed tomography (CT) analysis showed that all scaffolds generated similar amounts of new bone which was significantly greater than untreated controls. Interestingly, the spatial distribution of new bone within the defect area varied by scaffold group. MicroCT and histological analysis demonstrated healing restricted to the dural side in the hollow 500 microm group, whereas the solid 500 microm group demonstrated healing along the dural side and within the center of the defect. Solid 100 microm groups demonstrated healing along the dural layer, periosteal layer, and within the center of the defect. These results suggest that pore size and closed void volume may both play important roles in scaffold degradation patterns and associated bone healing.

Reactivation versus primary CMV infection after splenectomy in immunocompetent patients.

Acute CMV infection in the immunocompetent host is usually asymptomatic or produces only mild symptoms. CMV infection in immunocompromized patients, especially transplant recipients and those infected with HIV, is a result of profound lymphopenia or dysfunction of CD4+/CD8+ cells and can cause substantial rates of complication and death. We present a case of CMV infection in a previously healthy man who just had splenectomy for blunt trauma: a short incubation of the CMV disease, a strongly positive CMV antigenemia, severity of the disease including prominent lymphocytosis, massive hepatic sinusoidal infiltration, and retinitis. Splenectomy changed the immunological defense against the virus and brought the infection to nearly fulminant scale.

Malay midwives and witches.

This paper attempts to analyse professional rivalry and dissonance amongst traditional Malay midwives (bidan kampung) in the Northwest areas of Peninsular Malaysia. It elucidates how techniques of symbolic and ritual communication are carefully monitored by these female specialists, to develop regular clientele and professional credibility over time. However, since an integral element of Malay midwifery is protection from and mastery over mystical forces in nature and evil spirits harboured by witches, a midwife is also an exorcist with skills rather similar to the Malay bomoh (traditional medical practitioner, usually male) except that her range of knowledge of witchcraft is limited to diagnostic and curative rituals of spirit-possession, in infants and children, young unmarried women and pregnant mothers. Within a restricted population area, professional rivalries and competition amongst midwives regularly surface in oblique attacks of witchcraft accusations where the accused strives to maintain her credibility while her accuser gradually wins over her clientele. Significantly, codes of professionalism in traditional Malay midwifery are not only determined by skill and experience, but also religiousness (faith in Islam), benevolence, virtue, diligence and a sense of equality and fair-play in the practice of the trade. These qualities are seemingly lacking in witches who are conceived to be anti-Islamic, uncompromising, manevolent and destructive. Thus, government midwives who threaten the popularity of traditional midwives by being particularly active in their work or supervising and controlling midwives in an authoritarian way, are also labelled as witches. Generally, while midwifery and witchcraft reflect two forms of knowledge that are structurally opposed, in ideology and morality, they exist within the same sphere of ritual and symbolic communication where the practitioners aided by their clients, shift from one state of dissonance to another in an attempt to regulate behaviour.