Common Cause Research Articles

Challenges and diagnosis in therapy of secondary amenorrhoea in caesarean section patient with postpartum haemorrhage B-lynch sutures: a case report

Introduction and importance: International Federation of Gynecology and Obstetrics (FIGO) and WHO report the incidence of postpartum haemorrhage (PPH) reaches 1–10% and contributes to an increase in postpartum maternal mortality with uterine atony as the most common cause. B-Lynch method is a suturing technique to overcome PPH. Although this method has proven useful as an emergency life-saving measure, the post-procedure complications are still able to occur. Presentation of case: The patient was not menstruating for 14 months after giving birth through caesarean section with B-Lynch due to PPH. Before pregnancy, she had regular menstruation cycle and normal menstrual duration. Her general and gynaecological status were normal. Ultrasound showed the impression of uterine hypoplasia and endometrium that were difficult to assess while both ovaries were normal. Diagnostic hysteroscopy showed a severe degree of Asherman’s syndrome. The results of FSH, LH and estradiol were normal. Discussion: B-lynch suture is performed as a method to stop PPH in uterine atony. Secondary amenorrhoea occurs as a complication of B-lynch. Compression action of B-lynch can cause progressive myometrium necrosis resulting in synechiae and blockade of uterine blood flow. This will interfere with the development of the uterus. Intrauterine adhesions and amenorrhoea with normal levels of FSH, LH, and estradiol support the diagnosis of Asherman’s syndrome. Conclusion: This case shows that the B-Lynch procedure, which is the worldwide recommended method for treating postpartum haemorrhage due to its high success rate, can cause complications of Asherman’s syndrome and cause secondary amenorrhoea.

Spontaneous delayed CSF rhinorrhea associated with encephalocele following surgical resection of a giant frontoparietal meningioma, an extremely rare entity and overlook of English literature

Introduction and importance: Spontaneous cerebrospinal fluid (CSF) rhinorrhea without a history of head trauma is rare. The authors describe a scarce case of spontaneous, nontraumatic, delayed CSF rhinorrhea due to ethmoidal encephalocele associated with frontoparietal giant meningioma. Case presentation: A 49-year-old male complained of a slowly growing skull mass lasting 10 years since a blunt head trauma and progressive hemiparesis 3 months ago and was referred to our center. There was a heterogeneous extra-axial mass (77×77×70 mm) with calcified components at his right frontal lobe, demonstrating notable adjacent parenchymal edema and a midline shift to the left. There was a sizeable extra-axial mass (113×95×80 mm) in his right front-temporoparietal lobe associated with adjacent invasion to calvarium leading to the lytic and sclerotic appearance of the calvarial bone showing intense heterogeneous contrast enhancement and an adjacent enhancing dural tail. A considerable mass effect on the adjacent frontotemporal cortex is evident, with mild parenchymal edema leading to a notable midline shift to the left, right uncal herniation, and left ventriculomegaly. On postoperation day 5, the patient developed a recurrent CSF leak exacerbated by hydrocephalus. He was rescheduled to undergo endoscopic endonasal surgery and dural repair on postoperative day 7. The postoperative course was uneventful. Clinical discussion: Frontoparietal lobe encephaloceles represent the least common cause of spontaneous CSF rhinorrhea. Early diagnosis and surgical management remain crucial to minimize the subsequent complications. Conclusion: The ventricular anatomy and CSF fluid dynamics alteration following tumor surgical resection seem to contribute to an environment by which a herniated ethmoidal encephalocele developed a delayed nontraumatic CSF leak.

CRISPR‐based gene therapy for wet age‐related macular degeneration in mouse model

AbstractWet age‐related macular degeneration (AMD) is a common cause of vision loss in the elderly. It is characterised by choroidal neovascularisation (CNV), caused by overexpression of vascular endothelial growth factor (VEGF), resulting in abnormal vessel proliferation. Current clinical management predominantly relies on anti‐VEGF agents, which require frequent and costly injections. Clustered regularly interspaced short palindromic repeats (CRISPR) technology has emerged as a promising strategy for permanently suppressing angiogenesis by targeting the VEGF‐related pathway. Increased research suggests that disrupting this pathway holds potential for preventing CNV progression. This review provides an overview of the aetiology, classification and pathophysiology of wet AMD, followed by a concise summary of current gene editing research using the CRISPR/Cas system via viral vector delivery strategies to target ocular pro‐angiogenic factors, including Hif‐1α, VEGF and VEGFR. The importance of timely targeting of VEGFA is emphasised and the challenges associated with gene editing therapies are also highlighted.

Concussion Rates in Youth Lacrosse Players and Comparison With Youth American Football.

There has been little focus on concussions in youth lacrosse players in the United States. To provide a descriptive analysis of the epidemiology and incidence of concussions in youth lacrosse and compare the results with well-documented analyses of concussions in youth American football. Descriptive epidemiology study. Data on concussions in pediatric patients playing lacrosse from 2006 to 2019 were collected using the National Electronic Injury Surveillance System (NEISS). Weighted calculations and combined participation data obtained from membership in USA Lacrosse were used to estimate injury incidence. A comparison dataset was created using the NEISS data on youth football-related concussions. The cause of concussion was categorized into player-to-player, player-to-stick, player-to-ball, or player-to-ground contact. A total of 37,974 concussion injuries related to lacrosse were identified in players with a mean age of 14.5 ± 3.5 years; 70% of concussions occurred in boys. National participation in lacrosse increased from 2006 to 2011 by a mean of 10.3% annually, followed by a lower annual growth rate of 2.5% from 2012 to 2019. The overall incidence of concussion injuries increased over the study period (r = 0.314), with the incidence rate in boys being greater than that of girls from 2009 to 2013. The most common cause of concussion was player-to-ground contact for boys and player-to-ball or player-to-stick contact for girls. The mean annual concussion incidences in youth lacrosse and youth football were 443 and 355 per 100,000 participants, respectively. Over the study period, 16% of lacrosse injuries were diagnosed as concussions, a higher mean annual incidence per 100,000 participants than that of youth football (443 vs 355). The cause of concussion was different based on sex, with higher rates of player-to-ball or player-to-stick contact in female players versus player-to-ground contact in male players.

Advocating hormonal treatment to prevent adult in-fertility in patients diagnosed with congenital un-descended testes.

In 2007 the Nordic group came to the following unanimous conclusions: In general, hormonal treatment is not recommended, considering the poor immediate results and the possible long-term adverse effects on spermatogenesis. Thus, surgery is to be preferred. However, defective mini puberty inducing insufficient gonadotropin secretion is one of the most common causes of nonobstructive azoospermia in men suffering from congenital isolated unilateral or bilateral cryptorchidism. The extent of alteration in the unilateral undescended testis correlate with the contralateral descended testis, indicating that unilateral cryptorchidism is a bilateral disease. Idiopathic central hypogonadism explains the phenomenon of defective mini puberty in otherwise healthy cryptorchid boys. We therefore recommend hormonal treatment for cryptorchid boys with defective mini puberty. Gonadotropin releasing hormone agonist (GnRHa) treatment following surgery to correct cryptorchidism restores mini puberty via endocrinological and transcriptional effects and prevents adult infertility in most cases. Several genes are important for central hypogonadotropic hypogonadism in mammals, including many that are transcribed in both the brain and testis. At the molecular level, there is no convincing evidence that heat shock is responsible for the observed pathological testicular changes. Thus, impaired transformation of gonocytes is not the result of temperature stress but rather a hormonal imbalance. Cryptorchidism should therefore be considered a serious andrological problem that cannot be successfully treated by early orchidopexy alone.

Genes and pathways revealed by whole transcriptome analysis of milk derived bovine mammary epithelial cells after Escherichia coli challenge

Mastitis, inflammation of the mammary gland, is the costliest disease in dairy cattle and a major animal welfare concern. Mastitis is usually caused by bacteria, of which staphylococci, streptococci and Escherichia coli are most frequently isolated from bovine mastitis. Bacteria activate the mammary immune system in variable ways, thereby influencing the severity of the disease. Escherichia coli is a common cause of mastitis in cattle causing both subclinical and clinical mastitis. Understanding of the molecular mechanisms that activate and regulate the host response would be central to effective prevention of mastitis and breeding of cows more resistant to mastitis. We used primary bovine mammary epithelial cell cultures extracted noninvasively from bovine milk samples to monitor the cellular responses to Escherichia coli challenge. Differences in gene expression between control and challenged cells were studied by total RNA-sequencing at two time points post-challenge. In total, 150 and 440 (Padj < 0.05) differentially expressed genes were identified at 3 h and 24 h post-challenge, respectively. The differentially expressed genes were mostly upregulated at 3 h (141/150) and 24 h (424/440) post-challenge. Our results are in line with known effects of E. coli infection, with a strong early inflammatory response mediated by pathogen receptor families. Among the most significantly enriched early KEGG pathways were the TNF signalling pathway, the cytokine-cytokine receptor interaction, and the NF-kappa B signalling pathway. At 24 h post-challenge, most significantly enriched were the Influenza A, the NOD-like receptor signalling, and the IL-17 signaling pathway.

Adolescent Female with Acute-onset Abdominal Pain

Background: Sigmoid volvulus is a more common cause of abdominal pain in geriatric patients. It is an uncommon cause for a pediatric patient, especially when dealing with an adolescent patient. Here we discuss an uncommon presentation of sigmoid volvulus.&#x0D; Case Description: A 14-year-old female presents with sudden-onset abdominal pain found to have sigmoid volvulus on CT imaging. She eventually underwent sigmoidoscopy for reduction and was monitored for 24 hours post-procedure.&#x0D; Conclusion: This case demonstrates the importance of having a high index of suspicion when a patient presents with volvulus, especially with adolescence. Although rare, it should always be on the differential due to its high rate of mortality if diagnosed late.

Correlation Between the Clinical Diagnosis and Sonographic Diagnosis in Women with First-Trimester Vaginal Bleeding.

Vaginal bleeding is the most common cause of presentation at the emergency department in the first trimester. Clinical presentation helps determine the likely cause of first-trimester vaginal bleeding. However, ultrasound imaging is required to reach a definitive diagnosis. To determine the relationship between clinical diagnosis and ultrasonographic findings in women with first-trimester vaginal bleeding. A prospective longitudinal study was conducted on 94 pregnant patients with a history of bleeding per vagina (PV) in the first trimester by using transvaginal ultrasound. PV spotting was noted in 64.9% and heavy bleeding in 35.1%. The most common clinically associated symptom was abdominal pain (68, 72.3%), and the least common clinically associated symptom was vesicle expulsion (2.1%). The most common predisposing factor was fever (31, 33.0%). The most frequent clinical diagnosis was threatened abortion (48, 51.1%), and the least common clinical diagnosis was gestational trophoblastic disease (GTD) and inevitable abortion (1, 1.1%). The most common ultrasound diagnosis at the initial scan was incomplete abortion (19.2%), while at follow-up scans, it was threatened abortion (48, 51.1%). The overall concordance between clinical diagnosis and ultrasound was 38.8%, with both complete abortion and GTD showing a concordance of 100%. The least concordance was seen in missed abortions (25%). Clinical assessment is insufficient in the identification of the cause of vaginal bleeding due to the overall low concordance rate. A combination of clinical assessment and ultrasonography is required for decision-making in every case.

Diagnostic Contribution of Additional Sequences to the Evaluation of Cord Lesions in Patients with Cervical Spinal Multiple Sclerosis in Turkey: A Retrospective Study.

Multiple Sclerosis (MS) is the most common cause of non-traumatic disability in young adults. Spinal cord involvement is observed in 55-75% of patients with MS. To identify the strengths and shortcomings of sagittal phase-sensitive inversion recovery (PSIR), sagittal proton density/T2-weighted (PD/T2W), and axial turbo inversion recovery magnitude (TIRM) sequences in the detection of cervical MS plaques by comparing with routine sequences (axial and sagittal T2W, sagittal T1W, sagittal TIRM, fat-suppressed contrast T1W) and therefore determine their diagnostic contributions. A total of 48 patients in whom additional magnetic resonance imaging (MRI) sequences were obtained for the diagnosis of cervical MS were retrospectively identified and included in the study. A total of 111 MS plaques were analyzed in terms of visibility, number, size, border sharpness, and intensity ratio based on the routine and additional MRI sequences. The evaluation of the images was independently undertaken by two radiologists. The highest visibility was provided by sagittal PSIR, sagittal TIRM, and axial TIRM sequences (P < 0.05 for all additional sequences). Seven lesions in PD/T2W and four lesions in axial T2W sequences were unable to be detected. Lesions seen in sagittal and axial TIRM sequences were larger than the others. The sharpest borders were determined in the axial TIRM sequence, and the most diffuse borders in the PD/T2W sequence. In intensity ratio, the sagittal PSIR sequence revealed the most significant contrast difference. The sagittal PSIR sequence may improve the detection of cervical MS plaques due to the improved visibility and intensity ratios. The axial TIRM sequence may be more useful than routine axial T2W in the evaluation of visibility, border sharpness, and size measurement of MS plaques.

PREDICTORS OF THE FORMATION OF NEUROLOGICAL DISORDERS IN PREMATURE INFANTS

Premature newborns requiring observation and examination and treatment in the intensive care unit are at high risk for the development of perinatal brain lesions. Congenital pneumonia and early neonatal sepsis are one of the most common causes of perinatal morbidity and mortality in premature infants. According to various authors, the incidence of congenital pneumonia and early neonatal sepsis in children ranges from 4 to 20 per 1,000 live births.

Abstract B043: Radiolabelled Trastuzumab Fab as a theranostic agent for HER2 expressing breast cancer

Abstract Breast cancer is the most common cause of mortality among women worldwide. Among all subtypes, HER2-positive breast cancers are highly aggressive and have poor prognosis. Surgical resection is choice of treatment. However, surgery may not be possible if disease is widespread. Trastuzumab, a monoclonal antibody, is globally used for immunotherapy. It is a large sized molecule (141kDa) and show slow pharmacokinetics and high liver uptake. We have explored trastuzumab fragment as a radio-theranostic agent. Trastuzumab Fab was generated using Papain enzyme tagged beads, incubation time 18 to 20 h at 850 rpm in phosphate buffer. Fab were collected with ultrafiltration device, cut off 30 kDa, in phosphate buffer pH 8. Quantification of Fab was done at 280 nm. Fab characterization was done using MALDI-TOF and SDS-PAGE. To enable radiolabelling of Fab with Ga-68 and Lu-177, Fab was conjugated with bifunctional chelator, DTPA. Fab-DTPA was separated by micro bio-spin P-6 chromatography columns and the average number of DTPA/Fab were calculated. Affinity of Fab conjugated Fab-DTPA for HER2 receptors was studied using the biolayer interferometry technique (BLI). Radiolabelling of Fab with Ga-68 for PET imaging and Lu-177 for therapy was optimized. Quality control included radiochemical purity using TLC in sodium citrate (pH 5) mobile phase, pyrogenicity using PTS, and sterility by tryptic soy broth culture media. Receptor affinity and apoptosis were studied with HER2 positive SKBR-3 cells using flow cytometry assay. The SKBR-3 cell (106) were cultured in 96 well plates and incubated with a known amount of Lu-177-DTPA-Fab (0- 18.5 MBq). First in human Ga-68 Fab PET/CT and Lu-177-Fab gamma camera images were acquired after obtaining clearance from Institutional Ethics Committee and inform signed consent. Patients were recruited with histopathological proven HER2 positive breast cancer and uptake on F-18 FDG PET/CT. Ga-68-DTPA-Fab (3.5-5 mCi) and 10-15 mCi Lu-177 DTPA-Fab was injected and images were acquired at 2/3 h and up to 7 days respectively. Dominant Fab peak at 45kDa on MALD-TOF, single band on SDS-PAGE (Non-reduced or reduced) have been obtained. Two DTPA/Fab were conjugated and confirmed by MALDI-TOF. BLI data showed Kd value of trastuzumab, Fab, and conjugated DTPA-Fab as 0.2 nM, 0.57 nM, and 20 nM for HER2. High labelling efficiency (≥98%) of Lu-177-DTPA-Fab and Ga-68-DTPA-Fab was achieved. Apoptosis (%) was 1.5%- 42.5% in SKBR-3 cells treated with Lu-177-DTPA-Fab. Both formulations were found sterile and pyrogen-free. Kidney and bladder activity of Ga-68/Lu-177-DTPA-Fab demonstrate renal clearance. Blood pool activity of both tracers were high. However, it was decreased, and lesion uptake was increased with time. All the lesions on Ga-68-DTPA-Fab, same as in F-18 FDG PET/CT, were picked up accept those near heart. Good lesion retention of Lu-177-DTPA-Fab was observed showing suitability for therapy. Fab-DTPA has potential to target HER2 receptor. It could be radiolabelled with Ga-68 for PET imaging and Lu-177 for targeted therapy. Citation Format: Jaya Shukla, Yogesh Rathore, Komalpreet Kaur, Santosh Irrinky, Rajender Kumar, Amanjit Bal, Bhagwant R Mittal. Radiolabelled Trastuzumab Fab as a theranostic agent for HER2 expressing breast cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr B043.

Kharameh cohort study (KHCS) on non-communicable diseases and preliminary findings of 3-year follow-up

PurposeThe Kharameh cohort study (KHCS) is one branch of the ‘Prospective Epidemiological Research Studies in Iran’, located in the south of Iran. The enrolment phase of KHCS spanned from April...

Gut microbes as medical signature for the effectiveness of immunotherapy in patients with advanced non-small cell lung cancer.

Lung cancer (LC) is the most common cause of cancer-related death worldwide and poses a severe threat to public health. Immunotherapy with checkpoint blockers has improved the outlook for advanced non-small cell lung cancer (NSCLC) therapy. For the treatment of patients with advanced NSCLC, antibodies such as anti-programmed death 1 (anti-PD1), anti-programmed death ligand 1 (anti-PD-L1), and anti-cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4) are of paramount importance. Anti-PD-1 and anti-PD-L1 monoclonal antibody therapies are used to block the PD-1/PD-L1 pathway and identify cancerous cells to the body's defenses. Antibodies directed against CTLA-4 (anti-CTLA-4) have also been shown to improve survival rates in patients with NSCLC. Currently, other immunotherapy approaches like neoadjuvant immune checkpoint inhibitors (NAICIs) and chimeric antigen receptor T-cell (CAR-T) therapies are applied in NSCLC patients. NAICIs are used for resectable and early stage NSCLC and CAR-T is used to find more useful epitope sites for lung tumors and destroy cancer cells. A patient's gut microbiota might influence how their immune system reacts to NSCLC immunotherapy. The majority of intestinal microbes stimulate helper/cytotoxic T cells, induce natural killer (NK) cells, activate various toll-like receptors (TLR), build up cluster of differentiation 8 (CD8), increase PD-1 production, and attract chemokine receptors towards cancer cells. Thus, they serve as immune inducers in NSCLC immunotherapy. Nonetheless, certain bacteria can function as immune suppressors by inhibiting DC proliferation, stopping CD28 trafficking, restoring CD80/CD86, increasing immunological tolerance, and upsetting Th17 cells. Therefore, they are prevalent in non-responders with NSCLC immunotherapy.

Effect of calcitriol supplementation on infectious biomarkers in patients with positive systemic inflammatory response: A Randomized Controlled Trial

Background: Sepsis is one of the common causes of hospitalization of patients in intensive care units. A significant role for vitamin D in sepsis has been proposed, which is due to its active metabolite, calcitriol. Aims: Evaluate the effect of calcitriol supplementation on infectious biomarkers, including procalcitonin and presepsin. Methods: Patients with sepsis were divided into intervention and control group. Patients in the intervention group received intravenous calcitriol daily for 3 days. The serum levels of procalcitonin and presepsin were evaluated on days 0, 3, and 5 after administration. Results: Fifty-two SIRS-positive patients were evaluated. Baseline characteristics, changes in Sequential Organ Failure Assessment (SOFA) score and blood levels of vitamin D were not significantly different between the two groups. Procalcitonin levels on day 5 and the differences between day 5 and 0 were significantly lower in the intervention group (P = 0.02). Presepsin on the third and fifth days in the intervention group was reduced, but in the control group, there was an ascending trend. However, there was no significant difference between the two groups on days 3 and 5 (P = 0.17 and P = 0.06, respectively) or between days 3 as well as 5 and the baseline presepsin level (P = 0.93 and P = 0.92, respectively). The ICU length of stay and 28-day mortality did not differ significantly either between the two arms of the study. Conclusions: Finally, the results of this study showed that the administration of intravenous calcitriol could reduce the levels of procalcitonin but did not have a significant effect on presepsin.

Can RESPiratory hospital Admissions in children with cerebral palsy be reduced? A feasibility randomised Controlled Trial pilot study protocol (RESP-ACT)

IntroductionThe most common cause of morbidity and mortality in children with severe cerebral palsy (CP) is respiratory disease. BREATHE-CP (Better REspiratory and Airway Treatment and HEalth in Cerebral Palsy) is...

The Sacroiliac Joint: A Current State-of-the-Art Review.

» The sacroiliac joint (SIJ) is a common cause of low back pain and should be included in the differential diagnosis.» Nonoperative treatment of sacroiliac pain is always the first line of therapy; however, when it is unsuccessful and becomes chronic, then recurrent nonoperative treatment becomes expensive.» Surgical treatment is cost-effective in appropriately selected patients. High-quality clinical trials have demonstrated statistically and clinically significant improvement compared with nonsurgical management in appropriately selected patients.» Spinal fusion to the sacrum increases degeneration of the SIJ and frequency of SIJ pain.

Abstract TMP47: Identifying and Categorizing Delays to Endovascular Treatment in Patients With Large Vessel Occlusions

Introduction: Early endovascular treatment (EVT) in patients with large vessel occlusions (LVO) is associated with better outcomes. Identifying and categorizing delays to EVT may reveal areas for improvement. Methods: We prospectively identified all patients who underwent EVT at our hospital between May 2022 - 2023. We determined eight steps in acute care: arrival, imaging, IR activation, ED release, arrival to IR, groin puncture, first pass, and recanalization. We classified patients as delayed if any interval exceeded their rolling six-month median. We created 12 categories and 36 subcategories of delays. We used t-test and odds ratios to compare intervals and outcomes between delayed and non-delayed patients. We analyzed subgroups based on causes of delay and location of presentation. Results: Out of 183 LVO patients who underwent EVT, 111 (61%) were delayed. There were no significant differences in age, gender, last known normal to arrival, NIHSS, thrombolytic use, or TICI scale. The delayed group had higher door to groin (99 min), door to device (126 min), and door to recanalization (159 min) compared to the non-delayed group (40, 65, 81 min; p &lt; 0.001). The most common causes of delay were: general case complexity (20%), which was associated with higher door to imaging (59 min, p &lt; 0.001) and imaging to IR activation (37 min, p = 0.03); after hours presentation (19%), which was associated with higher door to imaging (53 min, p = 0.02) and imaging to IR activation (36 min, p = 0.01); and procedural complexity (18%) which was associated with higher groin to device (34 min, p &lt; 0.001) and device to recanalization (53 min, p &lt; 0.001) when compared to other causes of delay. Between the delayed and non-delayed group, there was no significant difference in the length of stay, change in NIHSS at discharge, in-hospital mortality, disposition, or 90-day mRS. Subgroup analysis showed a trend towards higher mortality in delayed patients who presented after hours (OR 3.60 (CI) 0.92-14.10) or in-hospital (OR 2.41 (CI) 0.57-10.19). Conclusions: We determined seven intervals where delays can occur between arrival and recanalization of LVO patients. We created a system for categorizing delays that showed areas for improvement including after hours and in-hospital stroke evaluation.

Fibre-based fluorescence-lifetime imaging microscopy: a real-time biopsy guidance tool for suspected lung cancer.

Lung cancer is the most common cause of cancer-related deaths worldwide. Early detection improves outcomes, however, existing sampling techniques are associated with suboptimal diagnostic yield and procedure-related complications. Autofluorescence-based fluorescence-lifetime imaging microscopy (FLIM), a technique which measures endogenous fluorophore decay rates, may aid identification of optimal biopsy sites in suspected lung cancer. Our fibre-based fluorescence-lifetime imaging system, utilising 488 nm excitation, which is deliverable via existing diagnostic platforms, enables real-time visualisation and lifetime analysis of distal alveolar lung structure. We evaluated the diagnostic accuracy of the fibre-based fluorescence-lifetime imaging system to detect changes in fluorescence lifetime in freshly resected ex vivo lung cancer and adjacent healthy tissue as a first step towards future translation. The study compares paired non-small cell lung cancer (NSCLC) and non-cancerous tissues with gold standard diagnostic pathology to assess the performance of the technique. Paired NSCLC and non-cancerous lung tissues were obtained from thoracic resection patients (N=21). A clinically compatible 488 nm fluorescence-lifetime endomicroscopy platform was used to acquire simultaneous fluorescence intensity and lifetime images. Fluorescence lifetimes were calculated using a computationally-lightweight, rapid lifetime determination method. Fluorescence lifetime was significantly reduced in ex vivo lung cancer, compared with non-cancerous lung tissue [mean ± standard deviation (SD), 1.79±0.40 vs. 2.15±0.26 ns, P<0.0001], and fluorescence intensity images demonstrated distortion of alveolar elastin autofluorescence structure. Fibre-based fluorescence-lifetime imaging demonstrated good performance characteristics for distinguishing lung cancer, from adjacent non-cancerous tissue, with 81.0% sensitivity and 71.4% specificity. Our novel fibre-based fluorescence-lifetime imaging system, which enables label-free imaging and quantitative lifetime analysis, discriminates ex vivo lung cancer from adjacent healthy tissue. This minimally invasive technique has potential to be translated as a real-time biopsy guidance tool, capable of optimising diagnostic accuracy in lung cancer.

Achilles Tendon Stiffness in the Etiology of Sever Disease: A Shear Wave Elastography Study.

Sever disease is one of the most common causes of heel pain in growing children and adolescents. There is no consensus about etiology of Sever disease. The study comprised 41 participants aged 8 to 13 years who visited the orthopedic outpatient clinic: 17 patients with Sever disease and 24 asymptomatic children. The middle third segment of the body of the Achilles tendon and the calcaneal insertion zone were separately assessed. Five measuring points for the quantitative value of each point were randomly selected. The color scale used in the Young's modulus shows the lowest values in blue and the highest values in red. The mean values were used for the statistical analysis. Less elasticity was detected at the insertional site for the control group (4.02 kPa versus 3.65 kPa), the situation was reversed in the body of the Achilles tendon and the elasticity of the study group was less than that of the control group (241.0 kPa versus 260.5 kPa). However, no statistically significant difference was found between the groups. In conclusion, no difference was found in Achilles tendon elasticity between patients with Sever disease and healthy individuals in both the tendon body and the calcaneal insertionof the tendon. Achilles tendon elasticity has not been found to play a role in the etiology of Sever disease.

Diastology in the intensive care unit: Challenges for the assessment and future directions.

Myocardial dysfunction is common in patients admitted to the intensive care unit (ICU). Septic disease frequently results in cardiac dysfunction, and sepsis represents the most common cause of admission and death in the ICU. The association between left ventricular (LV) systolic dysfunction and mortality is not clear for critically ill patients. Conversely, LV diastolic dysfunction (DD) seems increasingly recognized as a factor associated with poor outcomes, not only in sepsis but also more generally in critically ill patients. Despite recent attempts to simplify the diagnosis and grading of DD, this remains relatively complex, with the need to use several echocardiographic parameters. Furthermore, the current guidelines have several intrinsic limitations when applied to the ICU setting. In this manuscript, we discuss the challenges in DD classification when applied to critically ill patients, the importance of left atrial pressure estimates for the management of patients in ICU, and whether the study of cardiac dysfunction spectrum during critical illness may benefit from the integration of left ventricular and left atrial strain data to improve diagnostic accuracy and implications for the treatment and prognosis.