A phase I dose escalation and expansion trial of the next-generation oral SERD camizestrant in women with ER-positive, HER2-negative advanced breast cancer: SERENA-1 monotherapy results.

BACKGROUND: SERENA-1 (NCT03616587) is a phase I, multi-part, open-label study of camizestrant in pre- and post-menopausal women with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. Parts A and B aim to determine the safety and tolerability of camizestrant monotherapy and define doses for clinical evaluation. PATIENTS AND METHODS: Women aged ≥18 years with metastatic or recurrent ER+, HER2- breast cancer, refractory (or intolerant) to therapy, were assigned 25 mg up to 450 mg once daily (QD; escalation) or 75, 150, or 300 mg QD (expansion). Safety and tolerability, antitumor efficacy, pharmacokinetics, and impact on mutations in the estrogen receptor gene (ESR1m) circulating tumor (ct)DNA levels were assessed. RESULTS: By 9 March 2021, 108 patients received camizestrant monotherapy at 25-450 mg doses. Of these, 93 (86.1%) experienced treatment-related adverse events (TRAEs), 82.4% of which were grade 1 or 2. The most common TRAEs were visual effects (56%), (sinus) bradycardia (44%), fatigue (26%), and nausea (15%). There were no TRAEs grade 3 or higher, or treatment-related serious adverse events at doses ≤150 mg. Median tmax was achieved ∼2-4 h post-dose at all doses investigated, with an estimated half-life of 20-23 h. Efficacy was observed at all doses investigated, including in patients with prior cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) and/or fulvestrant treatment, with and without baseline ESR1 mutations, and with visceral disease, including liver metastases. CONCLUSIONS: Camizestrant is a next-generation oral selective ER antagonist and degrader (SERD) and pure ER antagonist with a tolerable safety profile. The pharmacokinetics profile supports once-daily dosing, with evidence of pharmacodynamic and clinical efficacy in heavily pre-treated patients, regardless of ESR1m. This study established 75-, 150-, and 300-mg QD doses for phase II testing (SERENA-2, NCT04214288 and SERENA-3, NCT04588298).

Improved patient safety with a simplified operating room to pediatric intensive care unit handover tool (PATHQS).

Introduction: Patient handover is a crucial transition requiring a high level of coordination and communication. In the BC Children's Hospital (BCCH) pediatric intensive care unit (PICU), 10 adverse events stemming from issues that should have been addressed at the operating room (OR) to PICU handover were reported into the patient safety learning system (PSLS) within 1 year. We aimed to undertake a quality improvement project to increase adherence to a standardized OR to PICU handover process to 100% within a 6-month time frame. In doing so, the secondary aim was to reduce adverse events by 50% within the same 6-month period. Methods: The model for improvement and a Plan, Do, Study, Act method of quality improvement was used in this project. The adverse events were reviewed to identify root causes. The findings were reviewed by a multidisciplinary inter-departmental group comprised of members from surgery, anesthesia, and intensive care. Issues were batched into themes to address the most problematic parts of handover that were contributing to risk. Intervention: A bedside education campaign was initiated to familiarize the team with an existing handover standard. The project team then formulated a new simplified visual handover tool with the mnemonic "PATHQS" where each letter denoted a step addressing a theme that had been noted in the pre-intervention work as contributing to adverse events. Results: Adherence to standardized handover at 6 months improved from 69% to 92%. This improvement was sustained at 12 months and 3 years after the introduction of PATHQS. In addition, there were zero PSLS events relating to handover at 6 and 12 months, with only one filed by 36 months. Notably, staff self-reporting of safety concerns during handover reduced from 69% to 13% at 6 months and 0% at 3 years. The PATHQS tool created in this work also spread to six other units within the hospital as well as to one adult teaching hospital. Conclusion: A simplified handover tool built collaboratively between departments can improve the quality and adherence of OR to PICU handover and improve patient safety. Simplification makes it adaptable and applicable in many different healthcare settings.

Development and validation of a novel craniofacial statistical shape model for the virtual reconstruction of bilateral maxillary defects.

Bilateral maxillary defects are a challenge for fibula free flap reconstruction (FFFR) surgery due to limitations in virtual surgical planning (VSP) workflows. While meshes of unilateral defects can be mirrored to virtually reconstruct missing anatomy, Brown class c and d defects lack a contralateral reference and associated anatomical landmarks. This often results in poor placement of osteotomized fibula segments. This study was performed to improve the VSP workflow for FFFR using statistical shape modeling (SSM) - a form of unsupervised machine learning - to virtually reconstruct premorbid anatomy in an automated, reproducible, and patient-specific manner. A training set of 112 computed tomography scans was sourced from an imaging database by stratified random sampling. The craniofacial skeletons were segmented, aligned, and processed via principal component analysis. Reconstruction performance was validated on a set of 45 unseen skulls containing various digitally generated defects (Brown class IIa-d). Validation metrics demonstrated promising accuracy: mean 95th percentile Hausdorff distance of 5.47 ± 2.39 mm, mean volumetric Dice coefficient of 48.8 ± 14.5%, compactness of 7.28 × 105 mm2, specificity of 1.18 mm, and generality of 8.12 × 10-6 mm. SSM-guided VSP will allow surgeons to create patient-centric treatment plans, increasing FFFR accuracy, reducing complications, and improving postoperative outcomes.

Multiparametric MRI and T2/FLAIR mismatch complements the World Health Organization 2021 classification for the diagnosis of IDH-mutant 1p/19q non-co-deleted/ATRX-mutant astrocytoma.

AIM: To investigate whether T2-weighted imaging-fluid-attenuated inversion recovery (T2/FLAIR) mismatch, T2∗ dynamic susceptibility contrast (DSC) perfusion, and magnetic resonance spectroscopy (MRS) correlated with the histological diagnosis and grading of IDH (isocitrate dehydrogenase)-mutant, 1p/19q non-co-deleted/ATRX (alpha-thalassemia mental retardation X-linked)-mutant astrocytoma. MATERIALS: Imaging of 101 IDH-mutant diffuse glioma cases of histological grades 2-3 (2019-2021) were analysed retrospectively by two neuroradiologists blinded to the molecular diagnosis. T2/FLAIR mismatch sign is used for radio-phenotyping, and pre-biopsy multiparametric MRI images were assessed for grading purposes. Cut-off values pre-determined for radiologically high-grade lesions were relative cerebral blood volume (rCBV) ≥2, choline/creatine ratio (Cho/Cr) ≥1.5 (30 ms echo time [TE]), Cho/Cr ≥1.8 (135 ms TE). RESULTS: Sixteen of the 101 cases showed T2/FLAIR mismatch, all of which were histogenetically confirmed IDH-mutant 1p/19q non-co-deleted/ATRX mutant astrocytomas; 50% were grade 3 (8/16) and 50% grade 2 (8/16). None showed contrast enhancement. Nine of the 16 had adequate multiparametric MRI for analysis. Any positive value by combining rCBV ≥2 with Cho/Cr ≥1.5 (30 ms TE) or Cho/Cr ≥1.8 (135 ms TE) predicted grade 3 histology with sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 100%. CONCLUSION: The T2/FLAIR mismatch sign detected diffuse astrocytomas with 100% specificity. When combined with high Cho/Cr and raised rCBV, this predicted histological grading with high accuracy. The future direction for imaging should explore a similar integrated layered approach of 2021 classification of central nervous system (CNS) tumours combining radio-phenotyping and grading from structural and multiparametric imaging.

Prevalence of chronic non-cancer pain among military veterans: a systematic review and meta-analysis of observational studies.

INTRODUCTION: Chronic non-cancer pain is common among military veterans; however, the prevalence is uncertain. This information gap complicates policy decisions and resource planning to ensure veterans have access to healthcare services that align with their needs. METHODS: Following Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols, we searched MEDLINE, EMBASE, PsycINFO, CINAHL and Web of Science from inception to 9 February 2023 for observational studies reporting the prevalence of chronic non-cancer pain among military veterans. We performed random-effects meta-analysis to pool pain prevalence data across studies and used the Grading of Recommendations, Assessment, Development and Evaluation approach to evaluate the certainty of evidence. RESULTS: Forty-two studies that included 14 305 129 veterans were eligible for review, of which 28 studies (n=5 011 634) contributed to our meta-analysis. Most studies (90%; 38 of 42) enrolled US veterans, the median of the mean age among study participants was 55 years (IQR 45-62) and 85% were male. The pooled prevalence of chronic non-cancer pain was 45%; however, we found evidence of a credible subgroup effect based on representativeness of the study population. Moderate certainty evidence found the prevalence of chronic pain among studies enrolling military veterans from the general population was 30% (95% CI 23% to 37%) compared with 51% (95% CI 38% to 64%) among military veterans sampled from populations with high rates of conditions associated with chronic pain (p=0.005). CONCLUSION: We found moderate certainty evidence that 3 in every 10 military veterans from the general population live with chronic non-cancer pain. These findings underscore the importance of ensuring access to evidence-based care for chronic pain for veterans, and the need for prevention and early management to reduce transition from acute to chronic pain. Further research, employing a standardised assessment of chronic pain, is needed to disaggregate meaningful subgroups; for example, the proportion of veterans living with moderate to severe pain compared with mild pain.

Comparing the performance of full-field digital mammography and digital breast tomosynthesis in the post-treatment surveillance of patients with a history of breast cancer: A retrospective study.

INTRODUCTION: The purpose of our study was to compare the performance of 2D (FFDM) against 3D (FFDM plus DBT) examinations in the post-treatment surveillance of asymptomatic breast cancer survivors. METHODS: A list of women with a history of breast cancer who underwent screening mammography (2D or 3D) from 5/2017 to 5/2020 was retrieved. A total of 20,210 examinations were identified and performance metrics were compared. RESULTS: There were no statistically significant difference in cancer detection rate (CDR) (p = 0.38), recall rate (RR) (p = 0.087), or positive predictive value (PPV) (p = 0.74) between 2D vs. 3D examinations. Stratification by breast tissue identified no statistically significant difference in CDR (p = 0.581 and p = 0.428), RR (p = 0.230 and p = 0.205), or PPV (p = 0.908 and p = 0.721) between fatty/scattered and heterogeneous/extremely dense breast tissue when comparing 2D vs 3D examinations. Stratification by age did not identify a significant difference in RR or PPV between the two groups. CDR was statistically increased with 2D vs. 3D examinations in the 60-69 years group (p = 0.021). Stratification by race did not identify a significant difference in RR or PPV between the two groups. CDR was statistically increased with 3D vs. 2D examinations in white women (p = 0.036). Stratification by laterality (bilateral vs. unilateral post mastectomy) did not identify a significant difference in RR or PPV between the two groups. CDR was statistically increased in 2D vs. 3D examinations in unilateral studies (p = 0.009). CONCLUSION: For asymptomatic women with a history of breast cancer, there is no evidence that the addition of DBT to FFDM improves CDR, RR, or PPV. IMPLICATIONS FOR PRACTICE: More studies are needed concerning screening methodologies supplementing FFDM in the screening regimens of breast cancer survivors.

Zebrafish anterior segment mesenchyme progenitors are defined by function of tfap2a but not sox10.

The anterior segment is a critical component of the visual system. Developing independent of the retina, the AS relies partially on cranial neural crest cells (cNCC) as its earliest progenitors. The cNCCs are thought to first adopt a periocular mesenchyme (POM) fate and subsequently target to the AS upon formation of the rudimentary retina. AS targeted POM is termed anterior segment mesenchyme (ASM). However, it remains unknown when and how the switch from cNCC to POM or POM to ASM takes place. As such, we sought to visualize the timing of these transitions and identify the regulators of this process using the zebrafish embryo model. Using two color fluorescence in situ hybridization, we tracked cNCC and ASM target gene expression from 12 to 24hpf. In doing so, we identified a tfap2a and foxC1a co-expression at 16hpf, identifying the earliest ASM to arrive at the AS. Interestingly, expression of two other key regulators of NCC, foxD3 and sox10 was not associated with early ASM. Functional analysis of tfap2a, foxD3 and sox10 revealed that tfap2a and foxD3 are both critical regulators of ASM specification and AS formation while sox10 was dispensable for either specification or development of the AS. Using genetic knockout lines, we show that in the absence of tfap2a or foxD3 function ASM cells are not specified, and subsequently the AS is malformed. Conversely, sox10 genetic mutants or CRISPR Cas9 injected embryos displayed no defects in ASM specification, migration or the AS. Lastly, using transcriptomic analysis, we show that GFP + cNCCs derived from Tg [foxD3:GFP] and Tg [foxC1b:GFP] share expression profiles consistent with ASM development whereas cNCCs isolated from Tg [sox10:GFP] exhibit expression profiles associated with vasculogenesis, muscle function and pigmentation. Taken together, we propose that the earliest stage of anterior segment mesenchyme (ASM) specification in zebrafish is approximately 16hpf and involves tfap2a/foxC1a positive cNCCs.

Early versus Late acute graft pyelonephritis: A retrospective analysis of graft and patient outcomes.

BACKGROUND: Acute graft pyelonephritis (AGPN) is thought to affect graft and patient survival among renal transplant recipients. The objective was to compare outcomes among early AGPN (< 6 months from transplant) versus late AGPN (> 6 months from transplant). METHODS: This retrospective study analyzed 150 patients with AGPN dividing them into early and late AGPN from 2008 to 2016. Predictors of graft loss and mortality were compared using logistic regression analysis. Graft survival and patient survival were analyzed using Kaplan-Meyer survival plots. RESULTS: 55.3% (n = 83) had early AGPN and 44.7% (n = 67) had late AGPN. In early AGPN group, 13.3% had CMV disease on follow up compared to 3% in late AGPN group (p < 0.05). 26.5% had history of prolonged Foley's catheterization (> 5 days), 38.6% had prolonged DJ stent in-situ (> 2 weeks) following transplant surgery in the early AGPN compared to 7.5% and 19.4% respectively in the late AGPN group (p < 0.05). Recurrent GPN was more common in the late AGPN group - (35.8% versus 18.1%). Presence of renal abscess was predictive of graft loss in Univariate analysis (HR-6.12, p < 0.004). There was decreased death censored graft survival in the early AGPN group (p-0.035) with no significant difference in patient survival among the two groups. CONCLUSION: Occurrence of early AGPN had a significant impact on long term graft survival in renal transplant recipients with no significant effect on patient survival. This study underlines the paramount importance of the prevention of UTIs in renal transplant recipients.

The earliest known reported occurrence of dentigerous cyst in a six-month-old child.

The earliest reported case of the occurrence of a dentigerous cyst is described; the cyst surrounded an unerupted permanent tooth bud in a 6-month-old infant. Most commonly these lesions present between the second and third decades of life. They rarely occur before 10 years of age and have not been documented prior to 1 year of age. In the case reported here, the treatment instituted was extraction of the adjacent deciduous tooth and enucleation of the cyst along with the permanent molar tooth bud. Clinicians should be aware of the potential for this lesion to occur across a wide range of ages and the importance of prompt diagnosis and treatment to prevent complications and reduce morbidity.

Long-term outcomes of ablation, liver resection, and liver transplant as first-line treatment for solitary HCC of 3 cm or less using an intention-to-treat analysis: A retrospective cohort study.

Background: Curative-intent therapies for hepatocellular carcinoma (HCC) include radiofrequency ablation (RFA), liver resection (LR), and liver transplantation (LT). Controversy exists in treatment selection for early-stage tumours. We sought to evaluate the oncologic outcomes of patients who received either RFA, LR, or LT as first-line treatment for solitary HCC ≤ 3 cm in an intention-to-treat analysis. Materials and methods: All patients with solitary HCC ≤ 3 cm who underwent RFA, LR, or were listed for LT between Feb-2000 and Nov-2018 were analyzed. Cox regression analysis was then performed to compare intention-to-treat (ITT) survival by initial treatment allocation and disease-free survival (DFS) by treatment received in patients eligible for all three treatments. Results: A total of 119 patients were identified (RFA n = 83; LR n = 25; LT n = 11). The overall intention-to-treat survival was similar between the three groups. The overall DFS was highest for the LT group. This was significantly higher than RFA (p = 0.02), but not statistically significantly different from LR (p = 0.14). After multivariable adjustment, ITT survival was similar in the LR and LT groups relative to RFA (LR HR:1.13, 95%CI 0.33-3.82; p = 0.80; LT HR:1.39, 95%CI 0.35-5.44; p = 0.60). On multivariable DFS analysis, only LT was better relative to RFA (LR HR:0.52, 95%CI 0.26-1.02; p = 0.06; LT HR:0.15, 95%CI 0.03-0.67; p = 0.01). Compared to LR, LT was associated with a numerically lower hazard on multivariable DFS analysis, though this did not reach statistical significance (HR 0.30, 95%CI 0.06-1.43; p = 0.13). Conclusion: For treatment-naïve patients with solitary HCC ≤ 3 cm who are eligible for RFA, LR, and LT, adjusted ITT survival is equivalent amongst the treatment modalities, however, DFS is better with LR and LT, compared with RFA. Differences in recurrence between treatment modalities and equipoise in ITT survival provides support for a future prospective trial in this setting.

The European Rare Disease Network for HHT Frameworks for management of hereditary haemorrhagic telangiectasia in general and speciality care.

Hereditary haemorrhagic telangiectasia (HHT) is a complex, multisystemic vascular dysplasia affecting approximately 85,000 European Citizens. In 2016, eight founding centres operating within 6 countries, set up a working group dedicated to HHT within what became the European Reference Network on Rare Multisystemic Vascular Diseases. By launch, combined experience exceeded 10,000 HHT patients, and Chairs representing 7 separate specialties provided a median of 24 years' experience in HHT. Integrated were expert patients who focused discussions on the patient experience. Following a 2016-2017 survey to capture priorities, and underpinned by more than 40 monthly meetings, and new data acquisitions, VASCERN HHT generated position statements that distinguish expert HHT care from non-expert HHT practice. Leadership was by specialists in the relevant sub-discipline(s), and 100% consensus was required amongst all clinicians before statements were published or disseminated. One major set of outputs targeted all healthcare professionals and their HHT patients, and include the new Orphanet definition; Do's and Don'ts for common situations; Outcome Measures suitable for all consultations; COVID-19; and anticoagulation. The second output set span aspects of vascular pathophysiology where greater understanding will assist organ-specific specialist clinicians to provide more informed care to HHT patients. These cover cerebral vascular malformations and screening; mucocutaneous telangiectasia and differential diagnosis; anti-angiogenic therapies; circulatory interplays between anaemia and arteriovenous malformations; and microbiological strategies to counteract loss of normal pulmonary capillary function. Overall, the integrated outputs, and documented current practices, provide frameworks for approaches that augment the health and safety of HHT patients in diverse health-care settings.

Repeat resection in recurrent glioblastoma (3rGBM) Trial: A randomized care trial.

BACKGROUND: The prognosis for patients with recurrent glioblastoma (GBM) is dismal, and the question of repeat surgery at time of recurrence is common. Re-operation in the management of these patients remains controversial, as there is no randomized evidence of benefit. An all-inclusive pragmatic care trial is needed to evaluate the role of repeat resection. METHODS: 3rGBM is a multicenter, pragmatic, prospective, parallel-group randomized care trial, with 1:1 allocation to repeat resection or standard care with no repeat resection. To test the hypothesis that repeat resection can improve overall survival by at least 3 months (from 6 to 9 months), 250 adult patients with prior resection of pathology-proven glioblastoma for whom the attending surgeon believes repeat resection may improve quality survival will be enrolled. A surrogate measure of quality of life, the number of days outside of hospital/nursing/palliative care facility, will also be compared. Centers are invited to participate without financial compensation and without contracts. Clinicians may apply to local authorities to approve an investigator-led in-house trial, using a common protocol, web-based randomization platform, and simple standardized case report forms. DISCUSSION: The 3rGBM trial is a modern transparent care research framework with no additional risks, tests, or visits other than what patients would encounter in normal care. The burden of proof remains on repeat surgical management of recurrent GBM, because this management has yet to be shown beneficial. The trial is designed to help patients and surgeons manage the uncertainty regarding optimal care. CLINICAL TRIAL REGISTRATION: http://www. CLINICALTRIALS: gov. Unique identifier: NCT04838782.

Machine learning-based radiomic evaluation of treatment response prediction in glioblastoma.

AIM: To investigate machine learning based models combining clinical, radiomic, and molecular information to distinguish between early true progression (tPD) and pseudoprogression (psPD) in patients with glioblastoma. MATERIALS AND METHODS: A retrospective analysis was undertaken of 76 patients (46 tPD, 30 psPD) with early enhancing disease following chemoradiotherapy for glioblastoma. Outcome was determined on follow-up until 6 months post-chemoradiotherapy. Models comprised clinical characteristics, O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status, and 307 quantitative imaging features extracted from enhancing disease and perilesional oedema masks on early post-chemoradiotherapy contrast-enhanced T1-weighted imaging, T2-weighted imaging (T2WI), and apparent diffusion coefficient (ADC) maps. Feature selection was performed within bootstrapped cross-validated recursive feature elimination with a random forest algorithm. Naive Bayes five-fold cross-validation was used to validate the final model. RESULTS: Top selected features included age, MGMT promoter methylation status, two shape-based features from the enhancing disease mask, three radiomic features from the enhancing disease mask on ADC, and one radiomic feature from the perilesional oedema mask on T2WI. The final model had an area under the receiver operating characteristics curve (AUC) of 0.80, sensitivity 78.2%, specificity 66.7%, and accuracy of 73.7%. CONCLUSION: Incorporating a machine learning-based approach using quantitative radiomic features from standard-of-care magnetic resonance imaging (MRI), in combination with clinical characteristics and MGMT promoter methylation status has a complementary effect and improves model performance for early prediction of glioblastoma treatment response.

The systemic pro-inflammatory response: targeting the dangerous liaison between COVID-19 and cancer.

Inflammation is an established driver of severe SARS-CoV-2 infection and a mechanism linked to the increased susceptibility to fatal COVID-19 demonstrated by patients with cancer. As patients with cancer exhibit a higher level of inflammation compared with the general patient population, patients with cancer and COVID-19 may uniquely benefit from strategies targeted at overcoming the unrestrained pro-inflammatory response. Targeted and non-targeted anti-inflammatory therapies may prevent end-organ damage in SARS-CoV-2-infected patients with cancer and decrease mortality. Here, we review the clinical role of selective inhibition of pro-inflammatory interleukins, tyrosine kinase modulation, anti-tumor necrosis factor agents, and other non-targeted approaches including corticosteroids in their roles as disease-modulating agents in patients with COVID-19 and cancer. Investigation of these therapeutics in this highly vulnerable patient group is posited to facilitate the development of tailored therapeutics for this patient population, aiding the transition of systemic inflammation from a prognostic domain to a source of therapeutic targets.

Direct and Indirect endocrine-mediated suppression of human endometrial CD8+T cell cytotoxicity.

Regulation of endometrial (EM) CD8+T cells is essential for successful reproduction and protection against pathogens. Suppression of CD8+T cells is necessary for a tolerogenic environment that promotes implantation and pregnancy. However, the mechanisms regulating this process remain unclear. Sex hormones are known to control immune responses directly on immune cells and indirectly through the tissue environment. When the actions of estradiol (E2), progesterone (P) and TGFß on EM CD8+T cells were evaluated, cytotoxic activity, perforin and granzymes were directly suppressed by E2 and TGFß but not P. Moreover, incubation of polarized EM epithelial cells with P, but not E2, increased TGFß secretion. These findings suggest that E2 acts directly on CD8+T cell to suppress cytotoxic activity while P acts indirectly through induction of TGFß production. Understanding the mechanisms involved in regulating endometrial CD8+T cells is essential for optimizing reproductive success and developing protective strategies against genital infections and gynecological cancers.

Feto-maternal and renal outcomes of nephrotic syndrome in pregnancy.

Proteinuria can range from subnephrotic to nephrotic amounts during pregnancy, though nephrotic syndrome (NS) is rare (0.012%-0.025%). Without a renal biopsy, this distinction may be difficult at times. The objective of our study was assessing about renal and feto-maternal outcomes of these patients. This study was done in a tertiary-care hospital in north India from 2010 to 2019. We included all pregnant women with nephrotic-range proteinuria, with no signs or symptoms suggestive of pre-eclampsia. We studied their treatment modalities, renal, maternal, and fetal outcomes. Eighteen eligible pregnant women diagnosed with NS with no features suggestive of pre-eclampsia or associated comorbidities were included. The gestational age of presentation was 23.2 ± 1.36 weeks. The average proteinuria was 4.38 ± 0.76 g/day. The patients were managed conservatively without kidney biopsy. About 16.7% of pregnancies had worsening of hypertension and acute kidney injury which recovered after delivery. Anasarca was troublesome for four patients requiring fresh-frozen plasma infusion. All were managed conservatively; however, five patients were started on empirical immunosuppression, all five with steroids, while two required the addition of calcineurin inhibitors as well. All had live births, but 25.7% each had preterm and intrauterine growth restriction while one required neonatal intensive care unit admission. The degree of proteinuria had an impact on maternal and fetal outcomes, especially on risk to pre-eclampsia. NS during pregnancy needs evaluation and counseling. Majority of them can be managed conservatively yet specific therapies can safely be tried among symptomatic ones. Despite good outcomes, a sizeable risk to maternal and fetal complications can occur.

Evaluation of Serum Cystatin C as an Early Biomarker of Acute Kidney Injury in Patients with Acute Pancreatitis.

INTRODUCTION: Acute pancreatitis (AP) is an inflammatory process of pancreas with varying degree of involvement of regional tissues. The aim of this study was to investigate the potential use of serum cystatin C (Cys-C) for the early and accurate diagnosis of acute kidney injury (AKI) in patients of AP. MATERIALS AND METHODS: This was a prospective study conducted in 1 year. Total of 215 cases of AP fulfilling the inclusion criteria were enrolled in this study. Patients suffering from chronic pancreatitis, neoplasm, chronic liver disease, and chronic kidney disease were excluded from the study. Diagnosis of AP was based on the Atlanta classification 2012. All patients were classified into a non-AKI group (n = 152) and an AKI group (n = 38) according to the dynamic changes in serum creatinine levels. Serum Cys-C was measured by particle-enhanced immune nephelometric assay. RESULTS: By univariate logistic regression analysis, body mass index (BMI) (OR = 1.44, 95% CI: 1.23-1.68; p < 0.001), blood urea (OR = 1.15, 95% CI: 1.06-1.23; p < 0.001), Cys-C (OR = 1.04, 95% CI: 1.01-1.07; p < 0.05), serum calcium (OR = 0.59, 95% CI: 0.41-0.86; p < 0.05), and serum lactate dehydrogenase (LDH) (OR = 1.001, 95% CI: 1.0-1.001; p < 0.05) were the significant indicators for AKI in patients with AP. Using multivariate logistic regression analysis, urinary albumin and Cys-C were independent and significant indicators of AKI in patients with AP (OR = 1.026, 95% CI: 1.01-1.07; p < 0.01). Receiver operating characteristic (ROC) curve of serum Cys-C, for AKI in patient with AP could be identified with a sensitivity of 92.06% at specificity of 96.0% [area under the curve (AUC) = 0.96, 95% CI: 0.92-0.98] by baseline serum Cys-C (cutoff value = >32.32 mg/L). CONCLUSION: Increase of baseline serum Cys-C was associated with AKI in patients with AP. HOW TO CITE THIS ARTICLE: Patel ML, Shyam R, Bharti H, Sachan R, Gupta KK, Parihar A. Evaluation of Serum Cystatin C as an Early Biomarker of Acute Kidney Injury in Patients with Acute Pancreatitis. Indian J Crit Care Med 2020;24(9):777-782.

Novel bio-analytical technique for estimation of gamma oryzanol in rat plasma and brain homogenate using HPLC.

Gamma oryzanol, a component of rice bran oil is used for its anticancer and antihyperlipidemic properties. Bioanalytical method for rat plasma and brain homogenate was developed by HPLC system with a PDA detector in which drug elution was performed using C-18 column (4.6mm×150cm, 5µ) with 1% acetic acid in methanol: acetonitrile (65/35, v/v) as mobile phase at 1.2ml/min flow rate and detected at 326nm wavelength. Liquid liquid extraction method was chosen for extraction of oryzanol from plasma as well as brain homogenate as it provided highest recovery (95% in plasma, 85% in brain homogenate). Various extraction solvents for each body fluid were analysed, out of which highest recovery for plasma (95%), in acetone: IPA (1/1, v/v) and for brain homogenate (85%) in isopropyl alcohol (IPA) was observed. Observed linearity was between 500ng/mL-5000ng/mL. The interday and intraday precision (i.e. %RSD) was less than 10% and accuracy was±5%. Selectivity and matrix effect was checked and found as per USFDA criteria. Plasma samples were found to be stable over the analysis period, HQC samples were stable up to third cycle in freeze and thaw stability while LQC samples were stable over fourth cycle. The method proved to be simple, useful and is appropriate, for preclinical and experimental research.

Posttreatment Imaging in Patients with Head and Neck Cancer without Clinical Evidence of Recurrence: Should Surveillance Imaging Extend Beyond 6 Months?

BACKGROUND AND PURPOSE: Early detection of residual or recurrent disease is important for effective salvage treatment in patients with head and neck cancer. Current National Comprehensive Cancer Network guidelines do not recommend standard surveillance imaging beyond 6 months unless there are worrisome signs or symptoms on clinical examination and offer vague guidelines for imaging of high-risk patients beyond that timeframe. Our goal was to evaluate the frequency of clinically occult recurrence in patients with head and neck squamous cell carcinoma with positive imaging findings (Neck Imaging Reporting and Data Systems scores of 2-4), especially after 6 months. MATERIALS AND METHODS: This institutional review board-approved, retrospective data base search queried neck CT reports with Neck Imaging Reporting and Data Systems scores of 2-4 from June 2014 to March 2018. The electronic medical records were reviewed to determine outcomes of clinical and radiologic follow-up, including symptoms, physical examination findings, pathologic correlation, and clinical notes within 3 months of imaging. RESULTS: A total of 255 cases, all with Neck Imaging Reporting and Data Systems scores of 2 or 3, met the inclusion criteria. Fifty-nine patients (23%) demonstrated recurrence (45 biopsy-proven, 14 based on clinical and imaging progression), and 21 patients (36%) had clinically occult recurrence (ie, no clinical evidence of disease at the time of the imaging examination). The median overall time to radiologically detected, clinically occult recurrence was 11.4 months from treatment completion. CONCLUSIONS: Imaging surveillance beyond the first posttreatment baseline study was critical for detecting clinically occult recurrent disease in patients with head and neck squamous cell carcinoma. More than one-third of all recurrences were seen in patients without clinical evidence of disease; and 81% of clinically occult recurrences occurred beyond 6 months.