Small Intestinal Adenocarcinoma Involving a Submucosal Ectopic Lymph Node: A Case Report.

An 83-year-old male with a 55-year history of Crohn's disease, ileocecectomy 40 years prior, and naturopathic treatment for 25 years, presented with nausea, vomiting, and abdominal pain. Computed tomography of abdomen and pelvis demonstrated partial small intestinal obstruction and a 4.4-cm solid left renal mass. After 3 months of recurrent intestinal obstruction and development of a pericolonic abscess, resection of the ileocolonic anastomosis, abscess, and partial nephrectomy were performed. Histopathology demonstrated chronic active enteritis with fistula tract formation, consistent with Crohn's disease, and moderately differentiated small intestinal adenocarcinoma extending from mucosa into subserosa. A submucosal intestinal lymph node-like structure containing adenocarcinoma demonstrated endothelial venules, open marginal and intermediate sinuses, multiple polarized germinal centers, and partial capsule, consistent with an ectopic lymph node, also called a tertiary lymphoid organ. Twenty mesenteric lymph nodes were negative for carcinoma. The renal mass was a papillary renal cell carcinoma, Stage I. Intestinal tertiary lymphoid organs form in chronic immune activation and have variable structures ranging from simple B and T cell clusters to organized groups with high endothelial venules and lymphatic vessels. Encapsulation of tertiary lymphoid organs is rare, with some sources claiming this entity is never encapsulated. To our knowledge, this is the first report of small intestinal adenocarcinoma involving a submucosal encapsulated tertiary lymphoid organ, the prognostic significance of which is uncertain. We suggest increased awareness of intestinal tertiary lymphoid organs as an entity and further studies to delineate the effect their involvement by adenocarcinoma imparts on survival.

Evaluation of treatment response by Hopkins criteria on 18 F FDG PET-CT in patients of non-small cell lung cancer and its comparison with PERCIST response criteria.

AIM: To assess treatment response on FDG PET-CT in NSCLC patients by visual Hopkins score compared to PERCIST criteria and its potential for prognostication (or its correlation with survival). METHODS: Forty-four NSCLC patients with baseline and post-treatment FDG PET-CT scans were included, and interpreted using Hopkins and PERCIST criteria classifying patients into responders and non-responders. PERCIST-based CMR and PMR, and Hopkins Scores 1,2,3 were classified responders. PERCIST-based SD and PD and Hopkins scores 4,5 were classified as non-responders. Patients were followed upto 24 months after treatment completion. Cohen kappa for inter-criteria agreement and Kaplan Meir curve for overall survival (OS) analysis done. RESULTS: Out of 44 patients, PERCIST classified 27 (61.3%) as responders and 17 (38.6%) as non-responders, whereas Hopkins classified 12 patients (27.3%) as responders and 32 (72.7%) as non-responders. Inter-criteria agreement was low (kappa=0.19) with discordance in 45.5% of patients. Eighteen of 20 discordant cases were non-responders on Hopkins and responders on PERCIST, of which 88.8% were non-responders on follow-up as predicted by Hopkins. PERCIST responders had OS of 96.4% and 64.3% at 9 and 24 months, respectively, while non-responders OS was 93.5% and 40.2% at 9 and 24 months, respectively ( P -value = 0.049). However, responders on Hopkins had OS of 100% at 24 months, whereas non-responders had OS of 93.5% and 51.5% at 9 and 24 months, respectively ( P -value = 0.232). CONCLUSION: Semi-quantitative PERCIST and visual Hopkins criteria show low inter-criteria agreement, with visual criteria better-predicting survival in patients of NSCLC.

18 F-FDG PET-CT Evaluation of Primary Adrenal Ewing Sarcoma with Venous Thrombosis: An Unusual Presentation.

Ewing sarcoma (EWS) is primarily an osseous malignancy of childhood and young adults. Extraskeletal occurrence is less frequent and primary adrenal involvement is an even rare presentation. We present such a case of a 7-year-old boy diagnosed with adrenal EWS with associated venous thrombosis and pulmonary embolism detected on 18 F-fluorodeoxyglucose positron emission tomography-computed tomography scan.

Proteomic Analysis of Mucosal and Systemic Responses to SARS-CoV-2 Antigen.

The mucosal environment of the upper respiratory tract is the first barrier of protection against SARS-CoV-2 transmission. However, the mucosal factors involved in viral transmission and potentially modulating the capacity to prevent such transmission have not fully been identified. In this pilot proteomics study, we compared mucosal and systemic compartments in a South African cohort of vaccinated and unvaccinated individuals undergoing maxillofacial surgery with previous history of COVID-19 or not. Inflammatory profiles were analyzed in plasma, nasopharyngeal swabs, and nasal and oral tissue explant cultures, using Olink and Luminex technologies. SARS-CoV-2-specific antibody levels were measured in serum and tissue explants. An increased pro-inflammatory proteomic profile was measured in the nasal compartment compared to plasma. However, IP-10 and MIG levels were higher in secretions than in nasal tissue, and the opposite was observed for TGF-ß. Nasal anti-SARS-CoV-2 spike IgG correlated with mucosal MIG expression for all participants. A further positive correlation was found with IP-10 in BioNTech/Pfizer-vaccinated individuals. Systemic levels of anti-SARS-CoV-2 spike IgG elicited by this vaccine correlated with plasma IL-10, IL-6 and HBD4. Proteomic profiles measured in mucosal tissues and secretions using combined technologies could reveal correlates of protection at the mucosal portals of viral entry.

Mimicker of Osteoblastic Skeletal Metastasis on 18 F-FDG PET/CT Scan in a Case of Primary Mediastinal Germ Cell Tumor.

ABSTRACT: Primary mediastinal germ cell tumors are uncommon tumors, of which the nonseminomatous type is more likely to metastasize than the seminomatous type. Primary mediastinal germ cell tumors may also present with superior vena cava obstruction. Here, we present this case of primary mediastinal germ cell tumor with superior vena cava obstruction causing dilatation of collaterals in dorsal intravertebral venous plexus, which strongly mimics sclerotic skeletal lesions/metastasis on a Contrast-enhanced CT scan and also appears FDG avid on PET scan. Herein, we can differentiate the two by just a simple review of plain CT scan image.

Role of 18F-FDG PET/CT for detection of recurrence and metastases in renal cell carcinoma-are we underusing PET/CT?

PURPOSE The aim of this study was to compare 18F-fluorodeoxyglucose positron emission tomography- computed tomography (18F-FDG PET/CT) scan with computed tomography (CT) scan for detecting recurrence and metastasis in renal cell carcinoma patients. METHODS This retrospective study included patients from October 2013 to April 2017. Contrast-enhanced CT and PET/CT scans were compared and correlated with histopathology or/and follow-up studies. RESULTS Seventy-six patients, 60 males, were included. Lesions included primary renal, recurrent renal fossa lesions, lymph nodes, and distant metastatic lesions. Of 176 malignant lesions, CT detected 157 lesions; of which, 154 were true positive. Twenty-two false-negative lesions showed abnormal FDG uptake. CT scan had positive predictive value (PPV), negative predictive value (NPV), sensitivity, specificity, and accuracy of 98.0%, 37.1%, 87.5%, 81.2%, and 86.9%, respectively. All 176 lesions were PET/CT-positive. PET/CT had PPV, NPV, sensitivity, specificity, and accuracy of 100% each. The specificity and NPV of PET/CT were superior (P < .05). CONCLUSION PET/CT appears more accurate than CT scan for detecting metastasis and recurrence in renal cell carcinoma patients.

Incidental Detection of Mandibular Metastasis in Renal Cell Carcinoma on 99mTc-MIBI Scan.

ABSTRACT: MIBI scintigraphy is the most widely used modality to identify parathyroid adenomas preoperatively. However, MIBI is also known to accumulate in multiple benign and malignant lesions. In renal cell carcinoma, 30% of the patients present with distant metastasis, commonly lungs and bone; however, jaw bone metastases are extremely rare (<1% of oral malignancies). Here we present a rare case of MIBI-avid mandibular metastasis in bilateral renal cell carcinoma on 99mTc-MIBI scintigraphy. Thus, we emphasize on careful interpretation of 99mTc-MIBI scans, which in addition to parathyroid adenomas can incidentally detect concurrent malignant lesions.

Role of 18F-Fluorodeoxyglucose Positron Emission Tomography-Contrast-Enhanced Computed Tomography in Detection of Early Recurrence with Peritoneal Disease in a Case of Adrenocortical Carcinoma.

Adrenocortical carcinoma (ACC) is an uncommon and highly aggressive malignancy with a poor prognosis. Common sites of metastasis are lung, liver, and lymph nodes. We present a case of ACC in a 54-year-old female with an early disease recurrence of unusual hypervascular peritoneal metastatic abdominal-pelvic deposits detected on 18F-fluorodeoxyglucose positron emission tomography-contrast-enhanced computed tomography scan.

An Unusual Case of Urothelial Carcinoma of Bladder with Metastasis to Brain and Skeletal Muscles Evaluated on 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography.

Urothelial or transitional cell carcinoma is the most prevalent variant of urinary bladder carcinoma worldwide occurring in both men and women. There are a very few cases described in the literature with metastasis to skeletal muscles and even fewer cases with metastatic site in the brain. We present a case of high-grade urothelial carcinoma with metastasis to the left temporal lobe as well as multiple inter- and intra-muscular deposits in the left thigh.

Can 18F-FDG PET/CT alone or combined with radiology be used to reliably grade cartilage bone neoplasms for surgical decision making?

OBJECTIVE: Treatment of chondrosarcomas is grade based; intralesional curettage for grade 1 and resection for grade 2 or more. Currently used methods to determine grades before surgery are not highly accurate and create a dilemma for the surgeon. We have used a PET-CT combined with imaging to answer the following study questions: (1) Does SUVmax value from an 18F-FDG PET/CT correlate with the grade of chondrosarcoma? (2) Can a cutoff SUVmax value be used to differentiate between various grades of chondroid neoplasms with sufficient sensitivity and specificity? (3) Does SUVmax guide the clinician and add value to radiology in offering histologic grade-dependent management? METHODS: SUVmax values of patients with suspected chondrosarcoma were retrospectively correlated with the final histology grade for the operated patients. Radiologic parameters and radiology aggressiveness scores (RAS) were reevaluated and tabulated. RESULTS: Totally 104 patients with chondroid tumors underwent 18F-FDG PET/CT assessment. In total 73 had tissue diagnosis available as a pretreatment investigation. Spearman correlation indicated that there was a significant positive association between SUVmax and the final histology grading of chondroid tumors (correlation coefficient = 0.743; P < 0.01). SUVmax cutoff of 13.3 was 88.9% sensitive and 100% specific for diagnosing dedifferentiated chondrosarcomas. An RAS cutoff value of 3 or more could diagnose IHGCS with a sensitivity of 80.7% and specificity of 93.75%. Adding an SUVmax cutoff of 3.6 improves the sensitivity to 89.5%. CONCLUSION: SUVmax value can reliably help diagnose dedifferentiated chondrosarcoma and when added to the radiology score can improve the accuracy of grading chondrosarcoma.

An Unusual Case of Bilateral Ureteric Metastasis on PSMA PET-CT Scan in Carcinoma Prostate.

ABSTRACT: The most common locations for metastasis in adenocarcinoma of the prostate gland are lymph nodes, bone, lung, and liver. The involvement of the ureter as a site of metastasis in prostate carcinoma is quite rare in literature. Here we present a case involving bilateral ureters along with bilateral vesicoureteric junctions in a known case of prostate adenocarcinoma.

Archway Randomized Phase 3 Trial of the Port Delivery System with Ranibizumab for Neovascular Age-Related Macular Degeneration.

PURPOSE: To evaluate the safety and efficacy of the Port Delivery System with ranibizumab (PDS) for the treatment of neovascular age-related macular degeneration (nAMD). DESIGN: Phase 3, open-label, randomized, visual acuity assessor-masked noninferiority and equivalence trial. PARTICIPANTS: Patients with nAMD diagnosed within 9 months of screening previously treated with and responsive to anti-vascular endothelial growth factor therapy. METHODS: Patients were randomized 3:2 to treatment with the PDS with ranibizumab 100 mg/ml with fixed 24-week (Q24W) refill-exchanges (PDS Q24W) or intravitreal ranibizumab 0.5-mg injections every 4 weeks (monthly ranibizumab). MAIN OUTCOME MEASURES: Primary end point was change in best-corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study letter (letters) score from baseline averaged over weeks 36 and 40 (noninferiority margin,-4.5 letters; equivalence margin, ±4.5 letters). RESULTS: Archway enrolled 418 patients; 251 were randomized to and 248 received treatment with the PDS Q24W, and 167 were randomized to and received treatment with monthly ranibizumab. Baseline BCVA was 74.4 letters (PDS Q24W arm) and 75.5 letters (monthly ranibizumab arm; Snellen equivalent, 20/32). Adjusted mean change in BCVA score from baseline averaged over weeks 36 and 40 was +0.2 letters (standard error [SE], 0.5 letters) in the PDS Q24W arm and +0.5 letters (SE, 0.6 letters) in the monthly ranibizumab arm (difference, -0.3 letters; 95% confidence interval, -1.7 to 1.1 letters). PDS Q24W was both noninferior and equivalent to monthly ranibizumab. Of 246 PDS-treated patients assessed for supplemental ranibizumab treatment, 242 (98.4%) did not receive supplemental ranibizumab treatment before the first refill-exchange procedure, including 4 patients who discontinued treatment before the first refill-exchange procedure. Prespecified ocular adverse events of special interest were reported in 47 patients (19.0%) in the PDS Q24W arm and 10 patients (6.0%) in the monthly ranibizumab arm, which included, in the former arm, 4 (1.6%) endophthalmitis cases, 2 (0.8%) retinal detachments, 13 (5.2%) vitreous hemorrhages, 6 (2.4%) conjunctival erosions, and 5 (2.0%) conjunctival retractions. Most ocular adverse events in the PDS Q24W arm occurred within 1 month of implantation. CONCLUSIONS: Archway met its primary objective and PDS Q24W demonstrated noninferior and equivalent efficacy to monthly ranibizumab, with 98.4% of PDS-treated patients not receiving supplemental treatment in the first 24-week interval.

Heberprot-P en el tratamiento de las úlceras del pie diabético / Heberprot-P in the treatment of diabetic foot ulcers

RESUMEN Introducción: El pie diabético es una de las complicaciones más temible de la diabetes mellitus; es el causante del 80 % de las amputaciones no traumáticas a nivel mundial. Durante décadas se han utilizados diferentes tratamientos para la cicatrización del pie diabético; los factores de crecimiento han revolucionado esta terapéutica. La participación de un equipo multidisciplinario con el cumplimiento de los protocolos de actuación y el empleo del Heberprot-P disminuyen el índice de amputaciones en pacientes con esta afección. Objetivo: Presentar la evolución de pacientes con úlceras del pie diabético, en diferentes estadios clínicos, tratados con Heberprot-P. Desarrollo: Se presentan 3 casos clínicos; el primero es un paciente masculino, de 56 años, diabético, con amputación transmetatarsiana abierta en la cual se realizaron 16 aplicaciones del Heberprot-P y se colocó un injerto de piel, la lesión cerró en 45 días. El segundo es un paciente de 58 años, diabético e hipertenso, con lesión en el pie derecho, con una cirugía vascular previa; se realizaron 19 aplicaciones del Heberprot-P y la lesión cicatrizó en 49 días. El tercer caso es un paciente de 55 años, que ingresa por la una lesión extensa en el pie derecho, se le realizaron 22 aplicaciones de Heberprot-P, se logró el cierre de la lesión en 85 días y se evitó la amputación. Conclusiones: Los casos presentados evolucionaron de forma favorable con el tratamiento de Heberprot-P.

ABSTRACT Introduction: The diabetic foot is one of the most feared complications of diabetes mellitus; It is the cause of 80 % of non-traumatic amputations worldwide. For decades, different treatments have been used to heal diabetic foot; growth factors have revolutionized this therapy. The participation of a multidisciplinary team with compliance with the action protocols and the use of Heberprot-P decrease the rate of amputations in patients with this condition. Objective: To present the evolution of patients with diabetic foot ulcers, in different clinical stages, treated with Heberprot-P. Development: Three clinical cases are presented; The first is a male patient, 56 years old, diabetic, with open transmetatarsal amputation in which 16 applications of Heberprot-P were performed and a skin graft was placed, the lesion closed in 45 days. The second is a 58-year-old patient, diabetic and hypertensive, with a right foot injury, with previous vascular surgery; 19 applications of Heberprot-P were performed and the lesion healed in 49 days. The third case is a 55-year-old patient, who was admitted due to an extensive injury to his right foot, 22 applications of Heberprot-P were performed, closure of the injury was achieved in 85 days and amputation was avoided. Conclusions: The presented cases evolved favorably with Heberprot-P treatment.

Is there an inflammatory stimulus to human term labour?

Inflammation is thought to play a pivotal role in the onset of term and some forms of preterm labour. Although, we recently found that myometrial inflammation is a consequence rather than a cause of term labour, there are several other reproductive tissues, including amnion, choriodecidua parietalis and decidua basalis, where the inflammatory stimulus to labour may occur. To investigate this, we have obtained amnion, choriodecidual parietalis and decidua basalis samples from women at various stages of pregnancy and spontaneous labour. The inflammatory cytokine profile in each tissue was determine by Bio-Plex Pro® cytokine multiplex assays and quantitative RT-PCR. Active motif assay was used to study transcription activation in the choriodecidua parietalis. Quantitative RT-PCR was use to study the pro-labour genes (PGHS-2, PGDH, OTR and CX43) in all of the tissues at the onset of labour and oxytocin (OT) mRNA expression in the choriodecidual parietalis and decidua basalis. Statistical significance was ascribed to a P value <0.05. In the amnion and choriodecidua parietalis, the mRNA levels of various cytokines decreased from preterm no labour to term no labour samples, but the protein levels were unchanged. The choriodecidua parietalis showed increase in the protein levels of IL-1ß and IL-6 in the term early labour samples. In the amnion and decidua basalis, the protein levels of several cytokines rose in term established labour. The multiples of the median derived from the 19-plex cytokine assay were greater in term early labour and term established labour samples from the choriodecidua parietalis, but only in term established labour for myometrium. These data suggest that the inflammatory stimulus to labour may begin in the choriodecidua parietalis, but the absence of any change in prolabour factor mRNA levels suggests that the cytokines may act on the myometrium where we observed changes in transcription factor activation and increases in prolabour gene expression in earlier studies.

Progression of the atypical fibroxanthoma to pleomorphic dermal sarcoma in a heart transplant patient.

An 82-year-old man presented with a right scalp lesion which had been increasing in size. The patient's medical history was significant for a heart transplant 25 years before, and he was on chronic immunosuppression. Biopsy of the lesion showed atypical fibroxanthoma. The patient underwent an excision of the lesion with split thickness skin graft. Pathology showed fibroxanthoma with negative margins. Over the next 9 months, the patient developed new lesions, which were also excised to negative margins. However, with each new lesion, the histology demonstrated increasing dysplasia and ultimately pleomorphic sarcoma. The patient had a metastatic workup with CT of the chest, which was negative, and he underwent a radical scalpectomy, split thickness skin graft placement and adjuvant radiation therapy. The patient has not developed any new scalp lesions and no evidence of metastasis.

PKA and AKIP1 interact to mediate cAMP-driven COX-2 expression: A potentially pivotal interaction in preterm and term labour.

Previously, we showed that cAMP increased COX-2 expression in myometrial cells via MAPK. Here, we have extended these observations, using primary myometrial cell cultures to show that the cAMP agonist, forskolin, enhances IL-1ß-driven COX-2 expression. We then explored the role of A-kinase interacting protein (AKIP1), which modulates the effect of PKA on p65 activation. AKIP1 knockdown reversed the effect of forskolin, such that its addition inhibited IL-1ß-induced COX-2 mRNA expression and reduced the IL-1ß-induced increase in nuclear levels of p65 and c-jun. Forskolin alone and with IL-1ß increased IκBα mRNA expression suggesting that in the context of inflammation and in the presence of AKIP1, cAMP enhances p65 activation. AKIP1 knockdown reversed these changes. Interestingly, AKIP1 knockdown had minimal effect on the ability of forskolin to repress either basal OTR expression or IL-1ß-stimulated OTR mRNA expression. AKIP1 was up-regulated by IL-1ß, but not stretch and was repressed by cAMP. The mRNA expression of AKIP1 increased in early labour in tandem with an increase in COX-2 mRNA and protein. AKIP1 protein levels were also increased with inflammation and stretch-induced preterm labour. Our results identify a second important cAMP effector-switch occurring at term in human myometrium and suggest that a hitherto unrecognized interaction may exist between AKIP1, NFκB and AP-1. These data add to the proposition that cAMP acts as a key regulator of human myometrial contractility.

Plexiform Neurofibroma of the Uterus: A Case Report.

The female genital tract system is rarely affected by neurofibromatosis type 1 (NF1). Plexiform neurofibromas are congenital lesions that occur in patients with NF1. The vulva is the most frequent genital location but vaginal, cervical, uterine, and ovarian neurofibromas have rarely been reported. We describe a case of plexiform neurofibromas involving the uterine cervix in a patient with known NF1 that presented with chronic pelvic pain and heavy menstrual bleeding.

Pazopanib-Induced Asymptomatic Necrotizing Pancreatitis Diagnosed on 18F-FDG PET-CT Scan.

Multi-targeted tyrosine kinase inhibitor (TKI) pazopanib approved for the treatment of advanced soft tissue sarcoma (STS) has prolonged the estimated survival times and quality of life of patients. However, several adverse effects associated predominantly with the inhibition of the vascular endothelial growth factor receptor by these drugs may prove to be potentially life-threatening. One such rare adverse event with the use of pazopanib is acute pancreatitis. We present a case of asymptomatic necrotizing pancreatitis induced by pazopanib treatment for metastatic STS detected on 18F-FDG PET-CT imaging.

The interaction between protein kinase A and progesterone on basal and inflammation-induced myometrial oxytocin receptor expression.

Our previous work has shown myometrial PKA activity declines in term and twin-preterm labour in association with an increase in the expression of the oxytocin receptor (OTR). Here we investigate the action of cAMP/PKA in basal conditions, with the addition of progesterone (P4) and/or IL-1ß to understand how cAMP/PKA acts to maintain pregnancy and whether the combination of cAMP and P4 would be a viable therapeutic combination for the prevention of preterm labour (PTL). Further, given that we have previously found that cAMP enhances P4 action we wanted to test the hypothesis that changes in the cAMP effector system are responsible for the functional withdrawal of myometrial P4 action. Myometrial cells were grown from biopsies obtained from women at the time of elective Caesarean section before the onset of labour. The addition of forskolin, an adenylyl cyclase activator, repressed basal OTR mRNA levels at all doses and P4 only enhanced this effect at its highest dose. Forskolin repressed the IL-1ß-induced increase in OTR mRNA and protein levels in a PKA-dependent fashion and repressed IL-1ß-activation and nuclear transfer of NFκB and AP-1. P4 had similar effects and the combination P4 and forskolin had greater effects on OTR and NFκB than forskolin alone. While PKA knockdown had no effect on the ability of P4 to repress IL-1ß-induced OTR expression it reversed the repressive effect of the combination of P4 and forskolin and resulted in a greater increase than observed with IL-1ß alone. These studies suggest that cAMP acts via PKA to repress inflammation-driven OTR expression, but that when PKA activity is reduced, the combination of cAMP and P4 actually enhances the OTR response to inflammation, promoting the onset of labour and suggesting that changes in the cAMP effector system can induce a functional P4 withdrawal.

Changes in cAMP effector predominance are associated with increased oxytocin receptor expression in twin but not infection-associated or idiopathic preterm labour.

We previously reported that at term pregnancy, a decline in myometrial protein kinase A (PKA) activity leads to an exchange protein activated by cyclic AMP (Epac1)-dependent increase in oxytocin receptor (OTR) expression, promoting the onset of labour. Here, we studied the changes in the cyclic adenosine monophosphate (cAMP) effector system present in different phenotypes of preterm labour (PTL). Myometrial biopsies obtained from women with phenotypically distinct forms of PTL and the levels of PKA and OTR were examined. Although we found similar changes in the cAMP effector pathway in all forms of PTL, only in the case of twin PTL (T-PTL) was myometrial OTR levels increased in association with these results. Although there were several changes in the mRNA levels of components of the cAMP synthetic pathway, the total myometrial cAMP levels did not change with the onset of any subtype of PTL. With regards to the expression of cAMP-responsive genes, we found that the mRNA levels of 4 of the 5 cAMP-down-regulated genes were increased in T-PTL, similar to our findings in term labour. These data signify that although changes in the cAMP effector system were common to all forms of PTL, only in T-PTL were OTR levels increased. Similarly, the mRNA levels of cAMP-repressed genes were only increased in T-PTL supporting the concept that the decline in PKA levels influences myometrial function driving the onset of T-PTL.