Elevated midtrimester maternal plasma cytokines and preterm birth in patients with cerclage.

BACKGROUND: Cerclage is used for the prevention of spontaneous preterm birth; however, many patients at high risk of spontaneous preterm birth who have a cerclage in place eventually deliver before term. Although inflammation, measured by biomarkers (eg, cytokines), is a known risk factor for preterm delivery, evaluation of inflammation to determine pregnancy outcomes among patients with cerclage is poorly understood. OBJECTIVE: We sought to examine levels of maternal plasma inflammatory cytokines in the midtrimester among asymptomatic patients with a cervical cerclage (placed for any indication, including history, ultrasound, and examination indications) to evaluate the association between cytokine levels and preterm birth. STUDY DESIGN: This was a prospective cohort study of singleton, nonanomalous pregnancies who had a cerclage placed at <24 weeks of gestation from 2015 to 2018 at a single tertiary institution. Maternal plasma was collected perioperatively whenever possible. A custom magnetic bead Luminex cytokine assay was used to measure plasma inflammatory cytokine levels from these stored samples. The primary outcome was preterm birth at <37 weeks of gestation. A statistical cut point was calculated for each cytokine level to assess its optimal sensitivity and specificity for spontaneous preterm birth prediction. Patients were classified as having a "high" or "low" result for each cytokine based on this cut point. Receiver operating characteristic curve analysis was performed to estimate sensitivity, specificity, and positive and negative predictive values for spontaneous preterm birth prediction. Cox proportional-hazards regression modeled the association between the number of "high" inflammatory cytokines and gestational age at delivery, adjusting for confounders. Additional analyses were performed on the subgroup of patients with history-indicated cerclage and those with an ultrasound- or examination-indicated cerclage. RESULTS: A total of 43 patients participated in this study: 20 (46.5%) had spontaneous preterm birth (median, 30.9 weeks of gestation; interquartile range, 28.4-35.0). Plasma samples were collected at a median of 0 (interquartile range, -2 to 17) days concerning cerclage placement and a median of 18 (interquartile range, 13-21) weeks of gestation. Based on the statistical cut point for each cytokine level, 7% of patients had zero, 20.9% had 1, 18.6% had 2, 20.9% had 3, and 32.6% had ≥4 "high" cytokine results. Each additional "high" cytokine level was associated with earlier delivery (hazard ratio, 1.51; 95% confidence interval, 1.25-1.81) even after controlling for ultrasound- or examination-indication for cerclage (hazard ratio, 1.73; 95% confidence interval, 0.95-3.15). The presence of ≥4 "high" cytokine levels was 70% sensitive and 74% specific for predicting spontaneous preterm birth (area under the curve, 0.846; 95% confidence interval, 0.728-0.964; positive predictive value, 70%; negative predictive value, 73.9%). CONCLUSION: Among patients with a cervical cerclage, elevated midtrimester maternal plasma cytokine profiles were associated with subsequent preterm birth and can estimate the probability of preterm birth. Confirmation and refinement of this noninvasive panel may provide insight into improved selection of individuals who may benefit from cerclage placement and investigation of therapeutic strategies to mitigate midpregnancy inflammation.

Prevalence and Characteristics of Avoidant/Restrictive Food Intake Disorder in Adult Neurogastroenterology Patients.

BACKGROUND & AIMS: Avoidant/restrictive food intake disorder (ARFID) is a feeding and eating disorder that is characterized by avoidant or restrictive eating not primarily motivated by body shape or weight concerns. We aimed to determine the frequency of ARFID symptoms and study its characteristics and associated gastrointestinal symptoms. METHODS: We conducted a retrospective review of charts from 410 consecutive referrals (ages, 18-90 y; 73.0% female) to a tertiary care center for neurogastroenterology examination, from January through December 2016. Blinded coders (n = 4) applied Diagnostic and Statistical Manual of Mental Disorders, 5th edition, criteria for ARFID, with substantial diagnostic agreement (κ = 0.66). RESULTS: Twenty-six cases (6.3%) met the full criteria for ARFID and 71 cases (17.3%) had clinically significant avoidant or restrictive eating behaviors with insufficient information for a definitive diagnosis of ARFID. Of patients with ARFID symptoms (n = 97), 90 patients (92.8%) cited fear of gastrointestinal symptoms as motivation for their avoidant or restrictive eating. A series of binary logistic regressions showed that the likelihood of having ARFID symptoms increased significantly in patients with eating- or weight-related complaints (odds ratio [OR], 5.09; 95% CI, 2.54-10.21); with dyspepsia, nausea, or vomiting (OR, 3.59; 95% CI, 2.04-6.32); with abdominal pain (OR, 4.72; 95% CI, 1.87-11.81); or with lower GI diagnoses (OR, 2.40; 95% CI, 1.34-4.32). CONCLUSIONS: In a retrospective study of patients undergoing neurogastroenterology examinations, we found ARFID symptoms to be related most frequently to fear of gastrointestinal symptoms. Patients undergoing neurogastroenterology or motility examinations should be evaluated for symptoms of ARFID, particularly when providers consider dietary interventions.

Active monitoring of formaldehyde diffusion into histological tissues with digital acoustic interferometry.

The preservation of certain labile cancer biomarkers with formaldehyde-based fixatives can be considerably affected by preanalytical factors such as quality of fixation. Currently, there are no technologies capable of quantifying a fixative's concentration or the formation of cross-links in tissue specimens. This work examined the ability to detect formalin diffusion into a histological specimen in real time. As formaldehyde passively diffused into tissue, an ultrasound time-of-flight (TOF) shift of several nanoseconds was generated due to the distinct sound velocities of formalin and exchangeable fluid within the tissue. This signal was resolved with a developed digital acoustic interferometry algorithm, which compared the phase differential between signals and computed the absolute TOF with subnanosecond precision. The TOF was measured repeatedly across the tissue sample for several hours until diffusive equilibrium was realized. The change in TOF from 6-mm thick ex vivo human tonsil fit a single-exponential decay ([Formula: see text]) with rate constants that varied drastically spatially between 2 and 10 h ([Formula: see text]) due to substantial heterogeneity. This technology may prove essential to personalized cancer diagnostics by documenting and tracking biospecimen preanalytical fixation, guaranteeing their suitability for diagnostic assays, and speeding the workflow in clinical histopathology laboratories.

Immunohistochemistry of colorectal cancer biomarker phosphorylation requires controlled tissue fixation.

Phosphorylated signaling molecules are biomarkers of cancer pathophysiology and resistance to therapy, but because phosphoprotein analytes are often labile, poorly controlled clinical laboratory practices could prevent translation of research findings in this area from the bench to the bedside. We therefore compared multiple biomarker and phosphoprotein immunohistochemistry (IHC) results in 23 clinical colorectal carcinoma samples after either a novel, rapid tissue fixation protocol or a standard tissue fixation protocol employed by clinical laboratories, and we also investigated the effect of a defined post-operative "cold" ischemia period on these IHC results. We found that a one-hour cold ischemia interval, allowed by ASCO/CAP guidelines for certain cancer biomarker assays, is highly deleterious to certain phosphoprotein analytes, specifically the phosphorylated epidermal growth factor receptor (pEGFR), but shorter ischemic intervals (less than 17 minutes) facilitate preservation of phosphoproteins. Second, we found that a rapid 4-hour, two temperature, formalin fixation yielded superior staining in several cases with select markers (pEGFR, pBAD, pAKT) compared to a standard overnight room temperature fixation protocol, despite taking less time. These findings indicate that the future research and clinical utilities of phosphoprotein IHC for assessing colorectal carcinoma pathophysiology absolutely depend upon attention to preanalytical factors and rigorously controlled tissue fixation protocols.

Intramedullary cysticercosis.

Intramedullary cysticercosis is a rare form of cysticercosis in the central nervous system. A 55-year-old woman was admitted with low back pain, urinary incontinence, paraparesis and sensory deficit. Her MRI showed a well-defined intramedullary cystic lesion at T7 vertebral level with peripheral enhancement on contrast. She underwent a T7-T8 laminectomy and excision of the lesion. Histopathology revealed the lesion to be a cysticercus granuloma. A postoperative course of albendazole was given. The patient showed significant neurological improvement at follow-up.

Spontaneous intramural haematoma of the oesophagus: complete resolution on follow-up magnetic resonance imaging.

Spontaneous oesophageal dissection with intramural haematoma formation is an uncommon form of oesophageal injury with a characteristic imaging appearance. We report the clinical and radiological features of a 66-year-old woman presenting with acute onset chest pain, where computed tomography revealed a large haematoma within the wall of the thoracic oesophagus. The patient responded well to conservative management. Magnetic resonance imaging, performed seven days after the initial presentation, confirmed the resolution of the lesion.

Imaging in bronchopulmonary sequestration.

Bronchopulmonary sequestration is an uncommon pulmonary disorder characterized by an area of non-functioning abnormal lung tissue, which receives its blood supply from a systemic artery and characteristically has no connection with the tracheobronchial tree. The abnormal lung tissue is located within the visceral pleura of a pulmonary lobe in the intralobar variety, whereas the extralobar form has its own visceral pleura. The venous drainage of the extralobar type is usually into the systemic veins, whereas the intralobar type drains into the pulmonary veins. Radiological imaging plays a vital role in establishing the diagnosis, and even more importantly, in providing to the clinician a vascular roadmap essential for surgical planning. We present here a review of bronchopulmonary sequestration and also discuss the role of various imaging methods in the early diagnosis and management of these cases.

Protocol for the treatment of heterotopic bone formation in the temporomandibular joint.

The increase in patients with multiply operated temporomandibular joints (TMJs) has led to an increase in associated complications that respond unfavorably to additional attempts at correction. These can present as ankylosis and/or heterotopic bone formation. This has been recognized in other joint reconstruction, to a much more significant degree, and related to decreased vascularity, increased fibrosis and scarring, and decreased cellularity of the tissue in the joint space following multiple surgical procedures. Attempted correction of this problem can often lead to an increase in the etiology and to recurrence of the bone formation in spite of its debridement. Correction in other joints has evolved to include the use of thorough debridement of the heterotopic bone, alloplastic joint reconstruction, autologous fat grafting, and use of NSAIDs and low-dose radiatíon to decreaserecurrence.

Temporomandibular joint reconstruction with a custom total temporomandibular joint prosthesis: use in the multiply operated patient.

The purpose of this article is to report the development and use of the custom Christensen prosthesis (Garrett modification) for total temporomandibular joint reconstruction, its indications, protocol, adjunctive treatment and evolution to present design.

Vascularized osteochondral allografts in an immunosuppressed rat model: graft modulation and host immune tolerance.

The effects of 4 weeks of cyclosporin A (7 mg/kg per day) (CyA) on the survival of vascularized osteochondral grafts between rat strains [DA (donor) and Lewis (recipient)] and the presence and significance of host immune tolerance and graft antigen modulation after cessation of immunosuppression have been examined. Isografts (n = 12) survived without apparent abnormality for 8 weeks but showed signs of wasting after longer periods; unprotected allografts (n = 5) were rejected within 2 weeks. After 4 weeks of CyA, allografts remained healthy for at least 12 weeks but then deteriorated (n = 40). Antigen modulation was examined by graft removal at various intervals after cessation of CyA and reimplantation into a naive recipient (n = 14). All were rejected rapidly. Host tolerance was examined by graft removal at various periods after cessation of CyA and reimplantation of a fresh allograft (n = 15). Some of the second grafts survived at least 4 weeks without immunosuppression. The findings indicate development of incomplete host tolerance but no antigenic modulation of the graft.

Secondary ischaemia in rabbit skin flaps: the roles played by thromboxane and free radicals.

1. Biochemical mechanisms of ischaemia were investigated in rabbit skin flaps subjected to 2 h of primary ischaemia then, 24 h later, to 4 h of secondary ischaemia. During secondary ischaemia, flaps underwent either total ischaemia (arterial and venous blood supply occluded) or partial ischaemia (vein only occluded). Some of these flaps were treated at the time of reperfusion with the free-radical scavenger superoxide dismutase (EC 1.15.1.1) and/or the thromboxane synthetase inhibitor UK-38,485. 2. After 30 min of reperfusion, superoxide dismutase treatment significantly reduced blood thromboxane levels, elevated during ischaemia. Superoxide dismutase also reduced tissue levels of malonyldialdehyde and xanthine oxidase, indicators of free-radical damage, and restored the depleted tissue levels of superoxide dismutase. 3. UK-38,485 treatment failed to significantly alter any of these tissue free-radical parameters, although this agent significantly reduced blood thromboxane levels. 4. Combined superoxide dismutase plus UK-38,485 treatment was not significantly better than either treatment alone with respect to any parameter. 5. Partial ischaemia led to consistently higher levels of tissue free radicals and blood thromboxane than did total ischaemia. Thus partial ischaemia appears to result in greater free-radical damage than total ischaemia. 6. These results are consistent with the hypothesis that thromboxane acts as a mediator for free-radical damage in the ischaemic changes within the flap.

Interaction between thromboxane and free radical mechanisms in experimental ischaemic rabbit skin flaps.

The possible relationship between increased blood levels of thromboxane (TXA2) and tissue levels of free radicals during ischaemia was investigated. Rabbit epigastric skin flaps were subjected to 4 h of body temperature ischaemia, then infused with either the TXA2 synthetase inhibitor UK-38,485, the free radical scavenger superoxide dismutase (SOD), or both immediately prior to reperfusion. After 30 min of reperfusion, increases in the tissue levels of xanthine oxidase (XO) and malonyldialdehyde (MDA), both of which are indices of free radical generation and decreases in the tissue levels of SOD were found. SOD treatment completely restored XO, MDA and SOD levels to normal, whereas UK-38,485 only partially improved all three parameters. None of these changes was statistically significant. Effluent blood thromboxane B2 (TXB2) levels from the flap increased significantly (P less than 0.01) after ischaemia and were reduced significantly by both UK-38,485 and SOD (P less than 0.05). Combined UK-38,485 and SOD treatment was no better than treatment with either agent alone. ATP levels and oedema, which decreased and increased respectively due to ischaemia, were not significantly altered by drug infusion. These results suggest that free radical damage may be related to TXA2-generated thrombosis in ischaemia/reperfusion injury.

The scaphoid allograft: a new operation for treatment of the very proximal scaphoid nonunion or for the necrotic, fragmented scaphoid proximal pole.

This is a preliminary report of eight cases in which an allograft was used to replace half of the scaphoid. The indications for the procedure include the following: (1) Severe necrosis with fragmentation of the proximal pole, (2) Very proximal pole nonunion with small (less than 20% of the bone), unreconstructable proximal fragments, and (3) One case of severely comminuted intra-articular fracture of the scaphotrapezial joint and basal joint of the thumb caused by a gunshot wound. The Herbert scaphoid screw was used to provide rigid fixation. Follow-up ranged from 8 to 30 months. The result was good in six of eight patients. It should be emphasized that this is a preliminary report of the early experience with a new operation for salvage of difficult scaphoid fracture problems.