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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

Sickle cell disease (SCD) is the most common inherited disorder of hemoglobin worldwide. In Nigeria, the prevalence of SCD is 20–30/1000 live births. The burden of the disease has reached a level where it contributes 9–16% of the under-five mortality in many West African countries. This case series evaluated the chromatographic patterns and red blood cell indices of sickle cell homozygous patients. Red cell indices, blood film, sickle solubility test, and chromatographic patterns using Bio-Rad HPLC D10 were evaluated for both patients. Both the patients were Nigerian and HPLC showed HbS window 81.7 and 81.6% and increased HbF, that is, 7.5 and 8.8%. HbA2 was normal in both the cases, that is, 2.2 and 2.6%. Our data suggest that homozygous sickle cell disease is very common among the Nigerian population with an increase in HbF along with HbS and HbA2 is normal.

INTRODUCTION Neoadjuvant chemotherapy (NAC) is increasingly utilized in the treatment of Breast Cancer to downsize the tumour, improve surgical outcome and to achieve a complete pathological response (pCR). Current regimes result in response rates of 40-80% depending on the subtype of the tumour and the presence of pCR, noted in 13-26% patients, is considered an indicator of excellent prognosis. An additional advantage of NAC is the assessment of the in vivo chemo-responsiveness of the tumor.FDG-PET/CT (fluorodeoxyglucose positron emission tomography/computed tomography) provides morphologic as well as functional imaging. Preliminary studies suggest it provides a more accurate evaluation of tumour response compared to other techniques. Moreover, studies suggest its utility in identifying non-responders early during NAC so as to enable a switch to an alternate more effective regimen, thereby preventing avoidable toxicity associated with an ineffective drug regimen.In this study, we evaluated metabolic changes on FDG-PET after 2 cycles of NAC to predict pathological response to NAC. PATIENTS AND METHODS A prospective cohort of patients with newly diagnosed, non-metastatic, T1-4, N1-2/3 breast cancer, undergoing NAC from October 2012 to December 2019 at a tertiary referral center, were entered in this study. The tumor size was assessed by the same surgeon at baseline and after every cycle of NAC. FDG-PET/CT was performed before commencement of NAC (PET1) and after the 2nd cycle of NAC (PET2) and the early metabolic response (ΔSUV max i.e. change in maximum standardized uptake value) was determined. All patients underwent surgery on completion of NAC and the pathological response following surgery served as the reference standard for the evaluation of the therapy response on FDG-PET/CT. Patients were classified into Responders [pCR and Minimal Residual Disease (MRD)] and Non-responders [Gross Residual Disease (GRD)] as per the classification of Honkoop et al. Receiver operating characteristic analysis was performed to identify an optimal threshold value of reduction rate (RR) of maximum standardized uptake values (ΔSUVmax) to accurately predict pathological response. RESULTS Out of 135 patients, 4 patients had bilateral cancer, resulting in 139 breast lesions assessed at baseline by FDG PET CT of which 51.07% were Luminal, 21.58% HER2 + and 27.34% TNBC. The mean age was 49 years (range 27-72), 54.81% were premenopausal, 45.19% post-menopausal, 85 (61.15%) were stage II cancers and 54 (38.84%) had stage III cancers. The overall pCR rate was 24.46%, 65 (46.76%) were Responders (pCR+MRD) and 74 (53.23%) Non-responders (GRD). The mean PET1 SUVmax of the tumors in Responder group was 14.5 and of Non-responder group was 9.4. The mean PET2 SUVmax for Responders was 4.28 and Non-responders was 7.52. The RR after the second course of NAC (ΔSUV), was significantly higher for Responders, 62.38% (+24.79) as compared to Non-responders 25.81% (+57.57), (p CONCLUSIONS Metabolic change in FDG/PET-CT after 2 cycles of NAC can predict pathological response and, a ΔSUVmax of more than 51%, can differentiate Responders from Non- responders. Early determination of Non-responders could help identify a group which may benefit from an early change to an alternate regimen. Citation Format: Vinay Deshmane, Anuja Raniwala, Abhiyutthan Singh, Sachin Almel, Natasha Singh, Anita Bhaduri, Raj Jatale. The utility of PET-CT after the second cycle of neoadjuvant chemotherapy for monitoring early metabolic change to predict pathologic response [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-43.

Immunoglobin-G4 related disease (IgG4-RD) is an auto-immune inflammatory condition where patients present with a tumour-like mass that shows infiltration by plasma cell and subsequent fibrosis. It is a systemic condition that primarily involves the salivary glands, pancreas, kidneys, aorta, and retroperitoneum amongst other organs. Testicular involvement is a rare occurrence in this disease entity. A 55-year old male patient presented with the complaints of pain and swelling in the right scrotal region. Right-sided orchidectomy was carried out which on histopathology showed features suggestive of IgG4-RD which was later confirmed on immunohistochemistry. Whole body MRI revealed that no other organ was involved in the disease process in this patient. IgG4-RD has a variable clinical course and considerable overlap with its differentials. Imaging studies and serum IgG4 levels are neither confirmatory nor customarily diagnostic in every case. The only confirmatory diagnostic investigation is histopathological examination, which shows infiltration of IgG4+ plasma cells and fibrosis in the involved tissue. Whenever a mass-forming lesion with typical histomorphological features is encountered with involvement of multiple organs/anatomic sites, IgG4-related disease should be considered among the differentials, and clinicians of all disciplines should be familiar with this disease entity.

Sopite syndrome, centered around the drowsiness, lethargy, and irritability associated with motion sickness, can be induced by exposure to low-frequency motion. It is known that the vestibular apparatus plays an important role in the pathogenesis of motion sickness, which features several autonomic responses, and we have previously documented increased vestibular modulation of skin sympathetic nerve activity (SSNA) and an increase in skin blood flow associated with nausea. Here, we assessed whether imperceptibly slow sinusoidal motion, sufficient to induce sopite syndrome but not nausea, also modulates SSNA and skin blood flow. Participants were seated upright and exposed to a randomized set of sinusoidal linear accelerations, ranging from 0.03 Hz at 0.5 mG to 0.2 Hz at 5 mG, via a motorized platform. At all frequencies vestibular modulation was greater than the cardiac modulation of SSNA, but cardiac modulation and skin blood flow were both significantly lower during the motion than at baseline. We conclude that sopite syndrome is associated with a marked modulation of sympathetic outflow to the skin and cutaneous vasoconstriction.NEW & NOTEWORTHY Little is known about the autonomic consequences of sopite syndrome-the drowsiness that can be induced by low-amplitude cyclic motion. We recorded skin sympathetic nerve activity (SSNA) in seated participants exposed to slow sinusoidal linear acceleration (0.03-0.2 Hz), which preferentially activates hair cells in the utricular part of the otolithic organs, at amplitudes that generated no sensations of motion. At all frequencies, there was a clear vestibular modulation of SSNA and cutaneous vasoconstriction.

Pleural effusion results from excess fluid production or decreased absorption or both. Tuberculous (TB) pleural effusion is one of the most common forms of extrapulmonary TB. Here, we present the case of a 25-year-old female who presented with chest pain, fever, and decreased appetite from the past 5 months. Her X-ray showed fluid deposition in the lungs. Pleural fluid was sent for cytological examination, 4–5 smears were made and stained with Giemsa, H and E, and acid-fast bacilli (AFB) stain to rule out the tubercular cause of the pleural effusion. Cytological smears were full of degenerated and intact neutrophils. Ziehl–Neelsen stain showed the presence of AFB. However, Mycobacterium tuberculosis is rarely observed on direct examination by AFB staining in pleural fluid. The patient was started with antitubercular drugs and there was a significant improvement in the symptoms of the patient.

Introduction: COVID-19 in pregnancy has put all perinatal services at a slog pace due to restricted movement and fear associated with the unknown challenges that the entire world is facing. At a tertiary care center, where a majority of the cases are referred from adjoining areas, the incidence of complications encountered was more. The present study discusses the impact of COVID-19 in pregnant females and subsequent perinatal outcomes. Aims: To study the perinatal outcomes in COVID-19-diagnosed pregnancy. Type of study: Observational analytical study. Methodology: All the pregnant females with COVID-19-diagnosed pregnancy were studied for their demographic profile, symptomatology, laboratory results, obstetric outcome, and neonatal performance between June 18, 2020, and September 30, 2020. Results: A total of 114 obstetric patients were admitted at this particular level two-facility center. Out of this, 21 were symptomatic, 22 delivered by cesarean, two cases of ruptured tubal ectopic pregnancy were seen, two cases of ruptured uterus were there, nine cases were received in obstructed labor, four cases of incomplete abortion, and three stillbirths were reported at our center. None of the neonates was tested positive for COVID-19. Oligohydramnios was seen in 25.4% of cases and thrombocytopenia was a significant finding in 33.3% of the patients. Conclusion: COVID-19 has affected the obstetric population with varied outcomes all throughout pregnancy. Even in asymptomatic patients, complications like oligohydramnios and thrombocytopenia were seen. Obstetric services were poorly catered at the periphery as many patients were received in emergency as cases of obstructed labor and ruptured uterus. COVID-19 has negatively affected each dimension of service care provisions and the health and outcome of the obstetric population.

Solid papillary carcinoma of the breast (SPCB) is a distinctive form of papillary carcinoma that tends to occur in older women and usually has a favorable prognosis. We describe an invasive solid papillary carcinoma with extracellular and intracellular mucin and neuroendocrine differentiation in a 60-year old female. The cytological features have been also been highlighted with an insight on differentials that were helpful in its correct identification preoperatively.

Preterm birth remains the major cause of death and disability among children under the age of five. In developing countries antenatal preterm birth prevention clinics are set up to provide cervical length surveillance and/or treatment modalities such as cerclage or progesterone for those women with identified risk factors such as previous cervical treatment or preterm birth. However, 85% of women have no risk factors for PTB and currently there is no biomarker to screen women early in pregnancy. Women will present unexpectedly in threatened preterm labour and we have no choice but to adopt a re-active approach to their care by using predication and preparation strategies such as fetal fibronectin, tocolytic therapy and steroids. Despite these strategies approximately 15-20% of these women will give birth preterm before 34 weeks. There is a urgent need to re-design primary, secondary and tertiary prevention strategies for spontaneous preterm labour (sPTL) in singleton pregnancies aimed at identifying and addressing key gaps in clinical practice and research.

The Moyamoya disease [MMD] is a cereberovascular disorder characterized by progressive stenosis of intracranial internal carotid arteries and compensatory collateral formation at the base of the brain, mainly around the circle of Willis. When no particular associated risk factors can be identified, it is termed as Moyamoya disease. However, it may be associated with other neurological and extra- neurological disorders where it is termed as Moyamoya syndrome [MMS]. The condition is predominantly seen in East Asia and has bimodal age of distribution. The clinical manifestations are also age dependant with ischemia predominating in childhood and hemorrhagic manifestations being more common in adults. The pathogenesis is not entirely known, but genetic susceptibility is believed to be an important predisposing factor. The Suzuki staging system is most widely used for evaluation and staging of Moyamoya disease. The gold standard diagnostic modality is cerebral angiography but magnetic resonance imaging [MRA] has also been employed for diagnosis. Treatment is primarily surgical revascularization which is of 3 types: direct, indirect or combined revascularization. Although the role of revascularization surgery has been well established for ischemic MMD, the ideal surgical approach and the role of surgery in hemorrhagic MMD remains controversial.

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.

Neuropathic pain is chronic pain that follows nerve injury, mediated in the brain by elevated levels of the inflammatory protein tumor necrosis factor-alpha (TNF). We have shown that peripheral nerve injury increases TNF in the hippocampus/pain perception region, which regulates neuropathic pain symptoms. In this study we assessed pain sensation and perception subsequent to specific targeting of brain-TNF (via TNF antibody) administered through a novel subcutaneous perispinal route. Neuropathic pain was induced in Sprague-Dawley rats via chronic constriction injury (CCI), and thermal hyperalgesia was monitored for 10 days post-surgery. On day 8 following CCI and sensory pain behavior testing, rats were randomized to receive perispinal injection of TNF antibody or control IgG isotype antibody. Pain perception was assessed using conditioned place preference (CPP) to the analgesic, amitriptyline. CCI-rats receiving the perispinal injection of TNF antibody had significantly decreased CCI-induced thermal hyperalgesia the following day, and did not form an amitriptyline-induced CPP, whereas CCI-rats receiving perispinal IgG antibody experienced pain alleviation only in conjunction with i.p. amitriptyline and did form an amitriptyline-induced CPP. The specific targeting of brain TNF via perispinal delivery alleviates thermal hyperalgesia and positively influences the affective component of pain. Perspective This study presents a novel route of drug administration to target central TNF for treatment of neuropathic pain. Targeting central TNF through perispinal drug delivery could potentially be a more efficient and sustained method to treat patients with neuropathic pain.

Preterm labor (PTL) is the predominant cause of childhood morbidity and mortality. It has several phenotypes, each with a distinct etiology often involving inflammation. Here, in samples of reproductive tissues obtained in early PTL from women with phenotypically defined PTL, we examined the presence and distribution of inflammation and its relationship with prolabor gene expression. In chorioamnionitis (CA-PTL), cytokine protein concentrations were increased across all tissues; in idiopathic (I-PTL), the inflammatory changes were limited to the choriodecidua; inflammation was not a feature of placental abruption (PA-PTL). CA-PTL was associated with activation of p65 in the myometrium and AP-1 in the choriodecidua, and PA-PTL with CREB in the choriodecidua. In the myometrium, PGHS-2 mRNA level was increased in CA- and I-PTL; in the amnion, PGHS-2 mRNA level was higher in PA- and I-PTL, while in CA-PTL, OT, OTR mRNA, and CX-43 expression were increased. In the choriodecidua, PGHS-2 mRNA level was unchanged, but in CA and I-PTL, OT mRNA level were increased and OTR was reduced. These data show that CA-PTL is associated with widespread inflammation and prolabor gene expression. In contrast, in I-PTL, inflammation is limited to the choriodecidua, with discrete increases in PGHS-2 in the amnion and OT in the choriodecidua. Inflammation is not a feature of PA-PTL, which is associated with increased OT and OTR in the amnion.

Purpose To evaluate the safety and efficacy of the Port Delivery System with ranibizumab (PDS) for neovascular age-related macular degeneration (nAMD) treatment. Design Phase 2, multicenter, randomized, active treatment–controlled clinical trial. Participants Patients diagnosed with nAMD within 9 months who had received 2 or more prior anti–vascular endothelial growth factor intravitreal injections and were responsive to treatment. Methods Patients were randomized 3:3:3:2 to receive the PDS filled with ranibizumab 10 mg/ml, 40 mg/ml, 100 mg/ml, or monthly intravitreal ranibizumab 0.5-mg injections. Main Outcome Measures Time to first implant refill assessed when the last enrolled patient completed the month 9 visit (primary efficacy end point), improvement in best-corrected visual acuity (BCVA) and central foveal thickness (CFT), and safety. Results The primary analysis population was 220 patients, with 58, 62, 59, and 41 patients in the PDS 10-mg/ml, PDS 40-mg/ml, PDS 100-mg/ml, and monthly intravitreal ranibizumab 0.5-mg arms, respectively. Median time to first implant refill was 8.7, 13.0, and 15.0 months in the PDS 10-mg/ml, PDS 40-mg/ml, and PDS 100-mg/ml arms, respectively. At month 9, the adjusted mean BCVA change from baseline was ‒3.2 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, ‒0.5 ETDRS letters, +5.0 ETDRS letters, and +3.9 ETDRS letters in the PDS 10-mg/ml, PDS 40-mg/ml, PDS 100-mg/ml, and monthly intravitreal ranibizumab 0.5-mg arms, respectively. At month 9, the adjusted mean CFT change from baseline was similar in the PDS 100-mg/ml and monthly intravitreal ranibizumab 0.5-mg arms. The optimized PDS implant insertion and refill procedures were generally well tolerated. After surgical procedure optimization, postoperative vitreous hemorrhage rate was 4.5% (7/157; 1 event classified as serious). There was no evidence of implant clogging. Conclusions In the phase 2 Ladder trial, the PDS was generally well tolerated and demonstrated a dose response across multiple end points in patients with nAMD. The PDS 100-mg/ml arm showed visual and anatomic outcomes comparable with monthly intravitreal ranibizumab 0.5-mg injections but with a reduced total number of ranibizumab treatments. The PDS has the potential to reduce treatment burden in nAMD while maintaining vision.

We have previously shown that sinusoidal galvanic vestibular stimulation (sGVS), delivered at 0.2–2.0 Hz, evokes a partial entrainment of muscle sympathetic nerve activity (MSNA). Moreover, at lower frequencies of stimulation (0.08–0.18 Hz) sGVS produces two peaks of modulation: one (primary) peak associated with the positive peak of the sinusoidal stimulus and a smaller (secondary) peak associated with the trough. Here we assessed whether sGVS delivered at 0.05 Hz causes a more marked modulation of MSNA than at higher frequencies and tested the hypothesis that the primary and secondary peaks are of identical amplitude because of the longer cycle length. MSNA was recorded via tungsten microelectrodes inserted into the left peroneal nerve in 11 seated subjects. Bipolar binaural sGVS (±2 mA, 100 cycles) was applied to the mastoid processes at 0.05, 0.5, and 5.0 Hz (500 cycles). Cross-correlation analysis revealed two bursts of modulation of MSNA for each cycle at 0.05 and 0.5 Hz but only one at 5 Hz. There was a significant inverse linear relationship between vestibular modulation (primary peak) and frequency ( P < 0.0001), with the amplitudes of the peaks being highest at 0.05 Hz. Moreover, the secondary peak at this frequency was not significantly different from the primary peak. These results indicate that vestibular modulation of MSNA operates over a large range of frequencies but is greater at lower frequencies of sGVS. We conclude that the vestibular apparatus, through its influence on muscle sympathetic outflow, preferentially contributes to the control of blood pressure at low frequencies. NEW & NOTEWORTHY Vestibulosympathetic reflexes have been documented in experimental animals and humans. Here we show that sinusoidal galvanic vestibular stimulation, a means of selectively exciting vestibular afferents in humans, induces greater modulation of muscle sympathetic nerve activity when delivered at a very low frequency (0.05 Hz) than at 0.5 or 5.0 Hz.

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.

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.

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 andoxytocin (OT)mRNA expression in the choriodecidual parietalis and decidua basalis. Statistical significance was ascribed to a P value

Objective To report the histopathologic findings in the placentas of pregnant women with coronavirus disease-19 (COVID-19). Methods Pregnant women with COVID-19 delivering between April 2020 to June 2020 were identified. A retrospective study of placentas from COVID positive women received in the Department of Pathology, Monmouth Medical Center affiliate of Robert Wood Johnson Barnabas Health were examined and compared to control cohort of placentas from COVID negative women. The mothers were tested for coronavirus through nasopharyngeal swab upon admission to labor and delivery. The placentas from mothers who tested negative for the virus were sent to Pathology for examination based on the obstetrician's clinical judgment. Results Fifty surgical specimens (49 placentas and one product of conception) from patients positive for COVID-19 were examined and compared with fifty placentas from women with negative COVID-19 test results, who delivered during the same period. Most of the neonates had Appearance, Pulse, Grimace, Activity and Respiration (APGAR) scores of 9 and 9 at 1 and 5 minutes, respectively. Increased incidence of the COVID-19 positivity was noted in individuals with Rh-positive blood group A and Jewish heritage. Compared to the control group, the COVID-19 positive placentas showed increased features of malperfusion (microcalcifications, fibrin thrombi, syncytial knotting, and villous agglutination). However, there was no significant dysregulation in other variables, such as inflammation or coagulation. There was no case of maternal or fetal death (greater than eight weeks) or evidence of worse fetal outcomes noted due to a mother's positive COVID-19 status. Conclusions The COVID-19 positive placentas showed an increased prevalence of microcalcifications and fibrin thrombi, which may reflect an underlying hypercoagulable state induced by COVID-19 infection or could be due to excessive syncytiotrophoblast injury.

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-1β-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-1β-induced COX-2 mRNA expression and reduced the IL-1β-induced increase in nuclear levels of p65 and c-jun. Forskolin alone and with IL-1β 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-1β-stimulated OTR mRNA expression. AKIP1 was up-regulated by IL-1β, 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.

Fungal infections are very important infectious causes of granulomatous inflammation. Isolated subcutaneous fungal infections are uncommon and only seen in immunosuppressed patients or in those with other comorbidities. Such cases are usually mistaken as noninfectious benign lesions and fine-needle aspiration cytology (FNAC) can be used for an adequate diagnosis.

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.

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-1β 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-1β-induced increase in OTR mRNA and protein levels in a PKA-dependent fashion and repressed IL-1β-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-1β-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-1β 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.

Alcohol, tobacco, marijuana, and other substance use by adolescents can have a serious impact on their health and well-being according to the American Academy of Pediatrics (AAP, 2016). School social workers (SSW) are trained to conduct assessments and interventions with adolescents and families to improve their functioning and academic performance (National Association of Social Workers [NASW], 2003). Also, substance abuse prevention, identification, brief intervention, and referral to treatment are supported by the profession’s standards for working with adolescents (NASW, 2003). For SSW interested in incorporating these services into their work, this practice highlights column describes the importance and principles of conducting adolescent screening, brief intervention, and referral to treatment (SBIRT) for substance use. Highlights are drawn from Substance Use Screening and Intervention Implementation Guide: No Amount of Substance Use Is Safe for Adolescents (hereinafter, AAP Guide), a guide developed through a cooperative agreement between AAP and Centers for Disease Control and Prevention (CDC) (AAP, 2016).

High throughput sequencing has previously identified differentially expressed genes (DEGs) and enriched signalling networks in human myometrium for term (≥37 weeks) gestation labour, when defined as a singular state of activity at comparison to the non-labouring state. However, transcriptome changes that occur during transition from early to established labour (defined as ≤3 and >3 cm cervical dilatation, respectively) and potentially altered by fetal membrane rupture (ROM), when adapting from onset to completion of childbirth, remained to be defined. In the present study, we assessed whether differences for these two clinically observable factors of labour are associated with different myometrial transcriptome profiles. Analysis of our tissue (‘bulk’) RNA-seq data (NCBI Gene Expression Omnibus: GSE80172) with classification of labour into four groups, each compared to the same non-labour group, identified more DEGs for early than established labour; ROM was the strongest up-regulator of DEGs. We propose that lower DEGs frequency for early labour and/or ROM negative myometrium was attributed to bulk RNA-seq limitations associated with tissue heterogeneity, as well as the possibility that processes other than gene transcription are of more importance at labour onset. Integrative analysis with future data from additional samples, which have at least equivalent refined clinical classification for labour status, and alternative omics approaches will help to explain what truly contributes to transcriptomic changes that are critical for labour onset. Lastly, we identified five DEGs common to all labour groupings; two of which (AREG and PER3) were validated by qPCR and not differentially expressed in placenta and choriodecidua.

Myometrial inflammation is thought to have a pivotal role in the onset of term and some forms of preterm labour. This is based on the comparison of samples taken from women undergoing term elective CS prior to the onset of labour with those taken from women in established labour. Consequently, it is not clear whether myometrial inflammation is a cause or a consequence of labour. Our objective is to test the hypothesis that myometrial inflammation is a consequence of the onset of labour. To test this hypothesis, we have obtained myometrial samples from women at various stages of pregnancy and spontaneous labour and studied the activation of the AP-1 (c-Jun) and NFκB (p65) systems, cytokine mRNA expression and protein levels and inflammatory cell infiltration and activation. We found that the activation of p65 declined from preterm to term not in labour samples and thereafter increased in early and established labour. Cytokine mRNA expression and protein levels increased in established labour only. Using flow cytometry of myometrial tissue, we found that the number of neutrophils did increase with the onset of labour, but on tissue section, these were seen to be intravascular and not infiltrating into the myometrium. These data suggest that myometrial inflammation is a consequence rather than a cause of term labour.

Cardiac lymphoma as secondary extension of non-Hodgkin's lymphoma is described in 30% of autopsies; however, a few cases are diagnosed in vivo. Primary lymphoma of the heart and pericardium is rare, accounting for 1.3% of primary cardiac tumors and only 0.5% of extranodal lymphomas at autopsy. We present a unique case of 68-year-old man diagnosed with extranodal lymphoma with cardiac and abdominopelvic nodular deposits on 18-fluorodeoxyglucose positron emission tomography-computed tomography scan findings.

Abdominal aortic aneurysm (AAA) is an uncommon entity with high mortality. Etiologically, they are classified as inflammatory and infective (mycotic), the latter being less common. Clinical presentation, laboratory investigations, and treatment for these may considerably overlap. However, choice of management and the need for surgical intervention depends on factors such as size and progression of aneurysm, persistent symptoms, and presence or absence of distant pathology. Although computed tomography (CT) is the gold standard for AAA, in selected cases, especially in infected AAA, fluorodeoxyglucose positron emission tomography-CT can provide valuable information.

Oncogenic osteomalacia is a rare condition, with overproduction of fibroblast growth factor 23, leading to hypophosphatemia, phosphaturia. If it is associated with benign mesenchymal tumor, then resection of tumor is curable. Thus, detection and localization of the lesion are of utmost importance. We report a case, where 18F-FDG PET/CT scan was useful in detection of such occult lesion.

Pulmonary carcinosarcoma is an unusual biphasic tumor of the lung with carcinomatous and sarcomatous components. We report a case in a 71-year-old female who presented with a 13-cm lung mass. Microscopic examination revealed squamous cell carcinoma and chondrosarcoma with focal spindle cell atypia. In the most recent version of the World Health Organization (WHO) classification, carcinosarcoma is included in the category of sarcomatous neoplasms with a poorer prognosis than non-small cell lung carcinoma.

A 31-year-old man with a recent diagnosis of hypothyroidism presented to the emergency department as a transfer from the clinic for severe hypotension and hypoglycaemia. The patient endorsed a 2-week history of severe fatigue, weight loss, nausea and non-bloody emesis. He was aggressively hydrated and vasopressors were initiated. Despite these measures, the patient remained hypotensive and went into pulseless electrical activity. Return of spontaneous circulation was achieved via advanced cardiac life support protocol, and venous arterial extracorporeal membrane oxygenation (ECMO) was initiated. On day 3 of hospitalisation, the patient was weaned off ECMO support, and subsequent autoimmune work-up confirmed the diagnosis of autoimmune polyglandular syndrome type 2 with positive antiperoxidase antibodies (267 IU/mL), supporting the diagnosis of Hashimoto’s thyroiditis.

Background: In women with late preterm pre-eclampsia, the optimal time to initiate delivery is unclear because limitation of maternal disease progression needs to be balanced against infant complications. The aim of this trial was to determine whether planned earlier initiation of delivery reduces maternal adverse outcomes without substantial worsening of neonatal or infant outcomes, compared with expectant management (usual care) in women with late preterm pre-eclampsia. Methods: In this parallel-group, non-masked, multicentre, randomised controlled trial done in 46 maternity units across England and Wales, we compared planned delivery versus expectant management (usual care) with individual randomisation in women with late preterm pre-eclampsia from 34 to less than 37 weeks' gestation and a singleton or dichorionic diamniotic twin pregnancy. The co-primary maternal outcome was a composite of maternal morbidity or recorded systolic blood pressure of at least 160 mm Hg with a superiority hypothesis. The co-primary perinatal outcome was a composite of perinatal deaths or neonatal unit admission up to infant hospital discharge with a non-inferiority hypothesis (non-inferiority margin of 10% difference in incidence). Analyses were by intention to treat, together with a per-protocol analysis for the perinatal outcome. The trial was prospectively registered with the ISRCTN registry, ISRCTN01879376. The trial is closed to recruitment but follow-up is ongoing. Findings: Between Sept 29, 2014, and Dec 10, 2018, 901 women were recruited. 450 women (448 women and 471 infants analysed) were allocated to planned delivery and 451 women (451 women and 475 infants analysed) to expectant management. The incidence of the co-primary maternal outcome was significantly lower in the planned delivery group (289 [65%] women) compared with the expectant management group (338 [75%] women; adjusted relative risk 0·86, 95% CI 0·79–0·94; p=0·0005). The incidence of the co-primary perinatal outcome by intention to treat was significantly higher in the planned delivery group (196 [42%] infants) compared with the expectant management group (159 [34%] infants; 1·26, 1·08–1·47; p=0·0034). The results from the per-protocol analysis were similar. There were nine serious adverse events in the planned delivery group and 12 in the expectant management group. Interpretation: There is strong evidence to suggest that planned delivery reduces maternal morbidity and severe hypertension compared with expectant management, with more neonatal unit admissions related to prematurity but no indicators of greater neonatal morbidity. This trade-off should be discussed with women with late preterm pre-eclampsia to allow shared decision making on timing of delivery. Funding: National Institute for Health Research Health Technology Assessment Programme.

Although progesterone (P4) supplementation is the most widely used therapy for the prevention of preterm labor (PTL), reports of its clinical efficacy have been conflicting. We have previously shown that the anti-inflammatory effects of P4 can be enhanced by increasing intracellular cyclic adenosine monophosphate (cAMP) levels in primary human myometrial cells. Here, we have examined whether adding aminophylline (Am), a non-specific phosphodiesterase inhibitor that increases intracellular cAMP levels, to P4 might improve its efficacy using in vivo and in vitro models of PTL. In a mouse model of lipopolysaccharide (LPS)-induced PTL, we found that the combination of P4 and Am delayed the onset of LPS-induced PTL, while the same dose of P4 and Am alone had no effect. Pup survival was not improved by either agent alone or in combination. Myometrial prolabor and inflammatory cytokine gene expression was reduced, but the reduction was similar in P4 and P4/Am treated mice. There was no effect of the combination of P4 and Am on an ex vivo assessment of myometrial contractility. In human myometrial cells and myometrial tissue explants, we found that the combination had marked anti-inflammatory effects, reducing cytokine and COX-2 mRNA and protein levels to a greater extent than either agent alone. These data suggest that the combination of P4 and Am has a more potent anti-inflammatory effect than either agent alone and may be an effective combination in women at high-risk of PTL.

Enhanced recovery after surgery (ERAS) aims to improve perioperative care, hasten recovery to the normal physiological state and shorten length of stay (LoS). There is evidence that ERAS programmes following elective caesarean section (ELCS) confer benefit through faster return to physiological state and reduced LoS for mother and baby. Baseline audit of ELCS in 2013 revealed a mean LoS of 3 days. We piloted an ERAS discharge pathway promoting day 2 discharge, which rose from 5.0% to 40.2%. 19.2% of women went home on day 1. Many women fed back that they would prefer day 1 discharge. We hypothesised that a day 1 discharge pathway for low-risk women could benefit both women and services at our maternity unit. From October 2015, we developed a ‘fast-track pathway’ (FTP) using a Plan-Do-Study-Act approach. Between October 2015 and April 2016, we prospectively audited clinical outcomes, LoS and maternal satisfaction from all women placed on the FTP. We held regular multidisciplinary team meetings to allow contemporaneous analysis. Satisfaction was analysed by Likert scale at postoperative surveys. Women were identified in antenatal clinic after meeting predefined low-risk criteria. 27.3% of women (n=131/479) delivering by ELCS entered the FTP. 76.2% of women on the FTP were discharged on day 1. Mean LoS fell to 1.31 days. 94.2% of women who established breast feeding at day 1 were still breast feeding at 7 days. Overall satisfaction at day 7 was 4.71 on a 5-point Likert scale. 73.1% of women reported good pain control. Additional financial savings are estimated at £99 886 annually. There were no related cases of readmission. Day 1 discharge after ELCS is safe and acceptable in carefully selected, low-risk women and has high satisfaction. There may be resultant financial savings and improved flow through a maternity unit with no detected adverse effect on breast feeding, maternal morbidity or postnatal readmissions.

The Pediatric Brain Tumor Atlas (PBTA), created as a multi-center effort by the Children’s Brain Tumor Tissue Consortium (CBTTC) and Pacific Pediatric Neuro-Oncology Consortium (PNOC) and supported by the Gabriella Miller Kids First Data Resource Center (DRC), has the initial goal of comprehensively characterizing over 1,600 clinically annotated pediatric brain tumor samples and making the data publicly available to cancer researchers worldwide in near real time and without embargo. PBTA comprises comprehensive clinical data in addition to whole exome sequencing, whole genome sequencing (WGS), RNA sequencing (RNASeq), miRNA sequencing, and proteomics. To address the need to inform novel discovery and clinical implementation of genomic approaches for diagnostic/therapeutic purposes, PBTA utilizes the cloud-based research environment of the Gabriella Miller Kids First DRC to provide near real-time integration, dissemination, processing, and sharing of associated petabyte-scale harmonized data. The PBTA initiative leverages the DRC platform’s users to access their dbGAP approved use of TARGET and other pediatric cancer datasets hosted by NCI’s Cancer Genomics’ Cloud and Genomic Data Commons, allowing for cross-disease studies. Processed annotations is further enabled for the PBTA via PedcBioPortal, a data visualization/analysis application further integrating additional public and deposited datasets. In its first data release are over 30 different types of pediatric brain tumors representing over 1,000 subjects. This data is available on the Kids First DRC Portal and PedcBioPortal and users can seamlessly move between applications. Data types include those for matched tumor/normal samples, such as WGS, RNASeq, proteomics, longitudinal clinical data, imaging data (MRIs and radiology reports), histology slide images, and pathology reports. CBTTC/PNOC promote real-time data release and collaborative discovery via shared resources. The combination of cloud-based analytic platforms with data from both genomics and clinical practice serves to define a new paradigm for accelerated pediatric cancer translational research.

Coronavirus disease 2019 caused by severe acute respiratory syndrome-CoV-2 is an emerging infectious disease first identified in Wuhan City, Hubei Province, China, which subsequently spread as a global pandemic posing a global threat. As per World Health Organisation worldwide around 38 lac people have been infected and 2.6 lac people have died from the disease and in India 59,662 people are infected with 1981 deaths by May 9, 2020. It is feasible that potentially infectious specimens may be submitted in our laboratory those are the impending source of infection to the laboratory personnel. Using imaging equipment on coronavirus confirmed/suspected patient/carriers is a serious hazard for healthcare providers because there is a risk that the virus could remain on the surface of the computed tomography scan machines or ultrasound (US) probes/patient bed/couch. Here, we have enlisted the rigorous biosafety measures which if executed appropriately can significantly drop the chances of spread of infection to health care workers in these diagnostic sections.

The factors that initiate human labor are poorly understood. We have tested the hypothesis that a decline in cAMP/protein kinase A (PKA) function leads to the onset of labor. Initially, we identified myometrial cAMP/PKA-responsive genes (six up-regulated and five down-regulated genes) and assessed their expression in myometrial samples taken from different stages of pregnancy and labor. We found that the oxytocin receptor (OTR) was one of the cAMP-repressed genes, and, given the importance of OTR in the labor process, we studied the mechanisms involved in greater detail using small interfering RNA, chemical agonists, and antagonists of the cAMP effectors. We found that cAMP-repressed genes, including OTR, increased with the onset of labor. Our in vitro studies showed that cAMP acting via PKA reduced OTR expression but that in the absence of PKA, cAMP acts via exchange protein activated by cAMP (EPAC) to increase OTR expression. In early labor myometrial samples, PKA levels and activity declined and Epac1 levels increased, perhaps accounting for the increase in myometrial OTR mRNA and protein levels at this time. In vitro exposure of myometrial cells to stretch and IL-1β increased OTR levels and reduced basal and forskolin-stimulated cAMP and PKA activity, as judged by phospho-cAMP response element-binding protein levels, but neither stretch nor IL-1β had any effect on PKA or EPAC1 levels. In summary, there is a reduction in the activity of the cAMP/PKA pathway with the onset of human labor potentially playing a critical role in regulating OTR expression and the transition from myometrial quiescence to activation.

Sarcomas are a heterogeneous group of rare tumors and arise either from soft tissue or from bone. Soft-tissue sarcomas (STSs) initially metastasize to the lungs. Metastases to extrapulmonary sites such as liver, brain, and soft tissue distant from primary tumor usually develop later. However, cases with isolated adrenal metastasis without disseminated disease have been reported in literature. We present a case of primary myxoid liposarcoma of the lower limb, in which staging 18-F fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) scan detected a suspicious FDG avid adrenal lesion which eventually on resection was diagnosed as asymptomatic pheochromocytoma. Pheochromocytomas have been reported to demonstrate FDG uptake mimicking metastasis. Hence, while interpreting FDG PET-CT scans in the context of STSs, both the extrapulmonary metastatic potential of aggressive histological subtypes of sarcoma and rare possibility of FDG avid coexistent benign tumor should be taken into consideration.