Human distal airways contain a multipotent secretory cell that can regenerate alveoli.

The human lung differs substantially from its mouse counterpart, resulting in a distinct distal airway architecture affected by disease pathology in chronic obstructive pulmonary disease. In humans, the distal branches of the airway interweave with the alveolar gas-exchange niche, forming an anatomical structure known as the respiratory bronchioles. Owing to the lack of a counterpart in mouse, the cellular and molecular mechanisms that govern respiratory bronchioles in the human lung remain uncharacterized. Here we show that human respiratory bronchioles contain a unique secretory cell population that is distinct from cells in larger proximal airways. Organoid modelling reveals that these respiratory airway secretory (RAS) cells act as unidirectional progenitors for alveolar type 2 cells, which are essential for maintaining and regenerating the alveolar niche. RAS cell lineage differentiation into alveolar type 2 cells is regulated by Notch and Wnt signalling. In chronic obstructive pulmonary disease, RAS cells are altered transcriptionally, corresponding to abnormal alveolar type 2 cell states, which are associated with smoking exposure in both humans and ferrets. These data identify a distinct progenitor in a region of the human lung that is not found in mouse that has a critical role in maintaining the gas-exchange compartment and is altered in chronic lung disease.

Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase III MARIPOSA-2 study.

BACKGROUND: Amivantamab plus carboplatin-pemetrexed (chemotherapy) with and without lazertinib demonstrated antitumor activity in patients with refractory epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC) in phase I studies. These combinations were evaluated in a global phase III trial. PATIENTS AND METHODS: A total of 657 patients with EGFR-mutated (exon 19 deletions or L858R) locally advanced or metastatic NSCLC after disease progression on osimertinib were randomized 2 : 2 : 1 to receive amivantamab-lazertinib-chemotherapy, chemotherapy, or amivantamab-chemotherapy. The dual primary endpoints were progression-free survival (PFS) of amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy. During the study, hematologic toxicities observed in the amivantamab-lazertinib-chemotherapy arm necessitated a regimen change to start lazertinib after carboplatin completion. RESULTS: All baseline characteristics were well balanced across the three arms, including by history of brain metastases and prior brain radiation. PFS was significantly longer for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy [hazard ratio (HR) for disease progression or death 0.48 and 0.44, respectively; P < 0.001 for both; median of 6.3 and 8.3 versus 4.2 months, respectively]. Consistent PFS results were seen by investigator assessment (HR for disease progression or death 0.41 and 0.38 for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy, respectively; P < 0.001 for both; median of 8.2 and 8.3 versus 4.2 months, respectively). Objective response rate was significantly higher for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy (64% and 63% versus 36%, respectively; P < 0.001 for both). Median intracranial PFS was 12.5 and 12.8 versus 8.3 months for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy (HR for intracranial disease progression or death 0.55 and 0.58, respectively). Predominant adverse events (AEs) in the amivantamab-containing regimens were hematologic, EGFR-, and MET-related toxicities. Amivantamab-chemotherapy had lower rates of hematologic AEs than amivantamab-lazertinib-chemotherapy. CONCLUSIONS: Amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy improved PFS and intracranial PFS versus chemotherapy in a population with limited options after disease progression on osimertinib. Longer follow-up is needed for the modified amivantamab-lazertinib-chemotherapy regimen.

The Optical Signatures of Stochastic Processes in Many-Body Exciton Scattering.

We review our recent quantum stochastic model for spectroscopic lineshapes in the presence of a coevolving and nonstationary background population of excitations. Starting from a field theory description for interacting bosonic excitons, we derive a reduced model whereby optical excitons are coupled to an incoherent background via scattering as mediated by their screened Coulomb coupling. The Heisenberg equations of motion for the optical excitons are then driven by an auxiliary stochastic population variable, which we take to be the solution of an Ornstein-Uhlenbeck process. Here, we present an overview of the theoretical techniques we have developed as applied to predicting coherent nonlinear spectroscopic signals. We show how direct (Coulomb) and exchange coupling to the bath give rise to distinct spectral signatures and discuss mathematical limits on inverting spectral signatures to extract the background density of states.

Evolution of a local adolescent breast imaging service.

BACKGROUND: The pathway for paediatric patients (<18 years) with breast-related symptoms from primary care has evolved in recent years within our region. Historically patients were managed at their local site within the region with varied management approaches, including young patients undergoing potentially unnecessary breast biopsies, and timelines adopted. In 2020, the establishment of a dedicated paediatric breast clinic enabled a smoother referral process from primary care, an appropriate clinical setting for the patient population and a standardised management pathway. METHODS: A retrospective review was performed of patients aged between 9 and 18 years referred to the breast service between 2017 and 2022. We reviewed the trends in referral numbers over the years, referral indications, ultrasound findings and clinical outcomes. RESULTS: There has been a yearly increment in the number of patients referred, primarily driven by the 15-18 age group. The primary referral indication was a breast lump (52%), gynaecomastia (14%), abscess (9%), and breast pain (6%). The most prevalent ultrasound findings were a normal breast (41%) and a fibroadenoma (25%). Of patients presenting with a breast lump, 40% demonstrated a normal ultrasound and 46% fibroadenomas. Conservative management was opted for the majority of patients with simple fibroadenomas and gynaecomastia. An unusual case of dermatofibrosarcoma protruberans was identified, stressing the importance of prompt surgical review for rapidly growing masses. DISCUSSION: The new clinic structure has optimized under-18 patient care, reducing unnecessary interventions and alleviating pressure on adult breast units. We propose a management pathway that can be adopted at a local/regional level.

Impact and process evaluation of a primary-school Food Education and Sustainability Training (FEAST) program in 10-12-year-old children in Australia: pragmatic cluster non-randomized controlled trial.

BACKGROUND: Environmentally sustainable food initiatives accompanying nutrition education, such as the Food Education and Sustainability Training (FEAST) program, have gained traction in school settings. The aim of this trial was to conduct an impact and process evaluation of FEAST, to evaluate its effect on children's fruit and vegetable (F&V) intakes, and secondary outcomes: F&V variety consumed, nutrition knowledge, food preparation/cooking skills, self-efficacy and behaviours, food waste knowledge and behaviours, and food production knowledge. METHODS: FEAST was a 10-week curriculum-aligned program, designed to educate children about healthy eating, food waste, and sustainability, while teaching cooking skills. It was implemented by classroom teachers, face-to-face and online, during COVID-19 school closures, in Australia in 2021. A custom designed survey was used to collect baseline and post-intervention data from students. Generalised linear mixed models (GLMM) estimated group differences in pre-post changes for primary and secondary outcomes. Surveys were also administered to students and teachers to evaluate intervention implementation. RESULTS: Twenty schools participated and self-selected to be either intervention schools (n = 10) or wait-list control (WLC) schools (n = 10). A total of 977, 5th and 6th grade children participated in the trial with a mean age of 11.1 years (SD ± 0.7). The FEAST intervention, compared to WLC, did not result in significant increases in primary outcomes nor secondary outcomes. The process evaluation revealed FEAST was well-received by students and teachers, but COVID-19 school closures hindered implementation fidelity with a less intense program delivered under the constraints of pandemic lockdowns. CONCLUSIONS: This is the first cluster non-randomized controlled trial designed to independently evaluate FEAST in the primary-school setting. No evidence was found for improved F&V intakes in children, nor secondary outcomes. However, the positive process evaluation results suggest that further trials of the program are warranted. If implemented as originally designed (pre-pandemic), with increased duration and complemented by supporting school policies, such programs have the potential to improve children's daily F&V intakes, cooking skills and food waste behaviours. This would support the Australian curriculum and contribute to: health promotion within schools and sustainable schools initiatives, the national agenda to reduce food waste and sustainable development goals. AUSTRALIAN AND NEW ZEALAND CLINICAL TRIALS REGISTRY: [ACTRN12620001347954]- Registered prospectively on 14/12/2020.

The implementation of a hepatitis C testing service in community pharmacies: I-COPTIC consensus statement.

OBJECTIVES: This aimed to develop a blueprint for an effective community pharmacy Hepatitis C virus (HCV) testing service by producing a consensus statement. STUDY DESIGN: This was a modified Delphi process. METHODS: We recruited a heterogenous panel of experts (who had been involved in the setup or delivery of a community pharmacy HCV testing service) by purposive and chain referral methods. We had three rounds of a modified Delphi process. The first was a series of questions with free text responses and was analysed using thematic analysis, and the second and third were statements for the respondents to rate using a 7-point Likert scale. Consensus was predefined in a published protocol, and the results were reviewed by a public and patient involvement panel before the statement was finalised. RESULTS: We had 24 participants, including community and hospital-based pharmacists, local pharmaceutical committee members, charity representatives (Hepatitis C Trust), local clinical service lead, nurse specialists and doctors. The response rate of the first, second and third rounds were 100%, 96% and 88%, respectively. After the third round, we had 60 statements that reached consensus. We discussed the accepted statements with a patient and public involvement group. We used these statements to produce the I-COPTIC statement and a graphical summary. CONCLUSIONS: We developed a blueprint for the design of a gold standard community pharmacy HCV testing service. We believe this will support the successful implementation of community pharmacy testing for HCV. Community pharmacy testing is an important service to help achieve and maintain HCV elimination.

Effect of various antioxidants on ovarian tissue vitrification success in sheep.

BACKGROUND: Vitrification is a technique of cryopreservation that has been proposed as a promising alternative method for the preservation of oocytes, embryos and gonadal tissue. OBJECTIVE: To determine the effect of different antioxidants on post-thaw viability, morphology of retrieved oocytes and histology of vitrified ovarian tissue. MATERIALS AND METHODS: Four different antioxidants [i.e., resveratrol (20 uM), ZnSO4 (500 uM), curcumin (25 uM) and quercetin (1 uM)] were evaluated after their addition to the vitrification and warming media for their effects on the viability and morphology of retrieved oocytes and the histology of vitrified ovarian tissue. RESULTS: The number of oocytes retrieved from ovarian tissue from the above mentioned antioxidants and vitrified control were 34, 41, 26, 31 and 46 respectively. Among these the number of viable oocytes were found to be 24 (70.6%), 30 (73.1 %), 20 (76.9%), 26 (83.9%) and 33 (71.7%) and the number of oocytes found morphologically normal were 24 (70.6%), 26 (63.4%), 18 (69.2%), 21 (67.7%) and 34 (73.9%) for the above mentioned different antioxidants and vitrified control, respectively. Non-significant (P. > 0.05) differences were found between different treatment groups. Histomorphological evaluation of the ovarian cortical tissue showed that the percentage of intact follicles was significantly (P < 0.05) higher in the fresh control (84.19±3.9) than in other groups. Non-significant differences were found between resveratrol (50.2±5.5), curcumin (48.7±5.7), quercetin (51.6±4.8) and the vitrified control (42.7±6.1) groups; however, the ZnSO4 supplemented group (23.1±8.54) differed significantly (P < 0.05) from other antioxidant groups but was non-significant (P > 0.05) with the vitrified control group (42.7±6.1). CONCLUSION: The addition of antioxidants resveratrol, curcumin and quercetin at these concentrations tended to non-significantly improve the follicular integrity after vitrification. Doi.org/10.54680/fr24410110212.

Assessment of Symptomatic Dry Eye Disease among Postgraduate Medical Students of KIST Medical College and Teaching Hospital using an Ocular Surface Disease Index Questionnaire.

Background Symptomatic dry eye disease is a growing public health challenge especially among those who are visual display unit users and other long-time near activity workers. Increased screen time, prolonged use of face mask and shortage of sleep among resident doctors increases the risk of developing dry eye disease that can affect their learning and social abilities. Data is insufficient on the prevalence of dry eye disease among postgraduate medical students in Nepal. Objective To find out the prevalence of symptomatic dry eye disease using an ocular surface disease index questionnaire among postgraduate medical students of KIST Medical College and Teaching Hospital. Method A cross-sectional study was conducted among three batches postgraduate medical students until 2023 of KIST Medical College and Teaching Hospital, Imadol, Lalitpur. A single validated symptom-based questionnaire with 12 questions was used to assess symptomatic dry eye disease. Result Total of 110 post-graduate medical students with mean age of 30.4 years, 67 males and 43 females were enrolled. Among them, 68 (61.8%) had dry eye disease. Severe dry eye was the commonest followed by mild dry eye. There was statistically significant association between dry eye disease with the increased screen time and suboptimal durations of sleep. Conclusion About half of postgraduate students faced symptomatic dry eye disease. It is advisable for residents to have optimum sleep as possible, limit screen time and establish regular break time along their exposure.

Treatment outcomes 12 months after antiretroviral therapy initiation in Oman: a nationwide study from the Middle East.

ABSTRACTWe used routinely collected programme data on people living with HIV in Oman who started ART in 2014-2018 to assess retention on ART, viral suppression, attrition (mortality or loss to follow-up [LTFU]) and treatment failure (attrition or HIV viral load of > 1000 copies/mL) 12 months after antiretroviral therapy (ART) initiation. We identified 726 patients; 72% were male. Overall, 12 months retention on ART and viral suppression (intention-to-treat [ITT] analysis) were 85.7% and 74.5%, respectively. Attrition occurred in 14.3% (mortality of 7% and LTFU of 7.3%). Retention increased from 78.8% (93/118) to 90.6% (144/159) among patients who started ART in 2014 and 2018, respectively. Similarly, ITT and on-treatment analyses revealed that viral suppression 12 months after ART initiation increased from 57.6% (68/118) and 73.1% (68/93) among patients who initiated therapy in 2014-80.5% (128/159) and 88.8% (128/144) among patients started treatment in 2018, respectively. On multivariate analysis, older age, having "Other" as an HIV risk factor (compared to heterosexual) and receiving HIV care outside the capital Muscat independently predicted both attrition and treatment failure. Our findings have been useful in identifying factors at the individual and programme level that influenced the risk of attrition and treatment failure.

Exploring the use of masks for protection against the effects of wildfire smoke among people with preexisting respiratory conditions.

BACKGROUND: The impact of wildfire smoke is a growing public health issue, especially for those living with preexisting respiratory conditions. Understanding perceptions and behaviors relevant to the use of individual protective strategies, and how these affect the adoption of these strategies, is critical for the development of future communication and support interventions. This study focused on the use of masks by people living in the Australian community with asthma or chronic obstructive pulmonary disease (COPD). METHODS: Semi-structured phone interviews were undertaken with people living in the community aged 18 years and over. Participants lived in a bushfire-prone area and reported having been diagnosed with asthma or COPD. RESULTS: Twenty interviews were undertaken between July and September 2021. We found that, during wildfire episodes, there was an overwhelming reliance on closing windows and staying inside as a means of mitigating exposure to smoke. There was limited use of masks for this purpose. Even among those who had worn a mask, there was little consideration given to the type of mask or respirator used. Reliance on sensory experiences with smoke was a common prompt to adopting an avoidance behavior. Participants lacked confidence in the information available from air-quality apps and websites, however they were receptive to the idea of using masks in the future. CONCLUSIONS: Whilst COVID-19 has changed the nature of community mask use over the last couple of years, there is no guarantee that this event will influence an individual's mask behavior during other events like bushfires. Instead, we must create social support processes for early and appropriate mask use, including the use of air quality monitoring.

Vitamin D Deficiency and Acute Otitis Media among Children Visiting a Tertiary Care Centre in Eastern Nepal.

Background There have been various studies to draw out the association between acute otitis media (AOM) and vitamin D deficiency but the results are conflicting. Objective To explore the relationship between vitamin D deficiency and acute otitis media. Method The comparative cross-sectional study was conducted in which children aged five to fifteen years were included. Sixty children diagnosed with acute otitis media were kept in group A while 60 children diagnosed with conditions other than acute otitis media were included in Group B. Then the Vitamin D level was sent in both the groups and compared. Result Fifty-four participants in group A had an insufficient level of Vitamin D while six participants had a sufficient level of Vitamin D and none had an excess level of Vitamin D while in Group B, fiftywo participants had an insufficient level of Vitamin D while eight participants had a sufficient level of Vitamin D. The mean vitamin D of the cases was 22.12 ±7.896 ng/ml, and that of the controls was 22.58 ±7.056 ng/ml for the controls (p = 0.737). Conclusion Both the children with acute otitis media and without acute otitis media had lower levels of Vitamin D in similar proportions. Therefore, we can conclude that there is no association between Vitamin D level and acute otitis media.

THE GUT-BRAIN AXIS: IMPLICATIONS FOR NEUROLOGICAL DISORDERS, MENTAL HEALTH, AND IMMUNE FUNCTION.

A gut-brain axis (GBA) has a long history of conceptual development. Intestinal dysbiosis has now been recognized as a key player in the development of adult neurodevelopmental disorders, obesity, and inflammatory bowel disease. Recent developments in metagenomics suggest those nutrition and gut microbiotas (GM) are important regulators of the gut-brain communication pathways that cause neurodevelopmental and psychiatric problems in adulthood. Intestinal dysbiosis and neurodevelopmental disease outcomes in preterm newborns are being linked by recent research. Recent clinical investigations demonstrate that in critical care units, intestinal dysbiosis occurs before late-onset newborn sepsis and necrotizing enterocolitis. Strong epidemiologic data also shows a connection between necrotizing enterocolitis and extremely low birth weight babies' long-term psychomotor impairments and late-onset neonatal sepsis. The GBA theory suggests that intestinal bacteria may indirectly affect preterm newborns' developing brains. In this review, we emphasize the structure and function of the GBA and discuss how immune-microbial dysfunction in the gut affects the transmission of stress signals to the brain. Preterm babies who are exposed to these signals develop neurologic disorders. Understanding neuronal and humoral communication through the GBA may provide insight into therapeutic and nutritional strategies that may enhance the results of very low-birth-weight babies.

Evaluation of a novel CFTR potentiator in COPD ferrets with acquired CFTR dysfunction.

RATIONALE: The majority of chronic obstructive pulmonary disease (COPD) patients have chronic bronchitis, for which specific therapies are unavailable. Acquired cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction is observed in chronic bronchitis, but has not been proven in a controlled animal model with airway disease. Furthermore, the potential of CFTR as a therapeutic target has not been tested in vivo, given limitations to rodent models of COPD. Ferrets exhibit cystic fibrosis-related lung pathology when CFTR is absent and COPD with bronchitis following cigarette smoke exposure. OBJECTIVES: To evaluate CFTR dysfunction induced by smoking and test its pharmacological reversal by a novel CFTR potentiator, GLPG2196, in a ferret model of COPD with chronic bronchitis. METHODS: Ferrets were exposed for 6 months to cigarette smoke to induce COPD and chronic bronchitis and then treated with enteral GLPG2196 once daily for 1 month. Electrophysiological measurements of ion transport and CFTR function, assessment of mucociliary function by one-micron optical coherence tomography imaging and particle-tracking microrheology, microcomputed tomography imaging, histopathological analysis and quantification of CFTR protein and mRNA expression were used to evaluate mechanistic and pathophysiological changes. MEASUREMENTS AND MAIN RESULTS: Following cigarette smoke exposure, ferrets exhibited CFTR dysfunction, increased mucus viscosity, delayed mucociliary clearance, airway wall thickening and airway epithelial hypertrophy. In COPD ferrets, GLPG2196 treatment reversed CFTR dysfunction, increased mucus transport by decreasing mucus viscosity, and reduced bronchial wall thickening and airway epithelial hypertrophy. CONCLUSIONS: The pharmacologic reversal of acquired CFTR dysfunction is beneficial against pathological features of chronic bronchitis in a COPD ferret model.

Comparative transcriptomics in human COPD reveals dysregulated genes uniquely expressed in ferrets.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a progressive lung disease with poor treatment options. However, most mouse models of COPD produce a primarily emphysematous disease not recapitulating clinically meaningful COPD features like chronic bronchitis. METHODS: Wild-type ferrets (Mustela putorius furo) were divided randomly into two groups: whole body cigarette smoke exposure and air controls. Ferrets were exposed to smoke from 1R6F research cigarettes, twice daily for six months. RNA-sequencing was performed on RNA isolated from lung tissue. Comparative transcriptomics analyses of COPD in ferrets, mice, and humans were done to find the uniquely expressed genes. Further, Real-time PCR was performed to confirmed RNA-Seq data on multiple selected genes. RESULTS: RNA-sequence analysis identified 420 differentially expressed genes (DEGs) that were associated with the development of COPD in ferrets. By comparative analysis, we identified 25 DEGs that are uniquely expressed in ferrets and humans, but not mice. Among DEGs, a number were related to mucociliary clearance (NEK-6, HAS1, and KL), while others have been correlated with abnormal lung function (IL-18), inflammation (TREM1, CTSB), or oxidative stress (SRX1, AHRR). Multiple cellular pathways were aberrantly altered in the COPD ferret model, including pathways associated with COPD pathogenesis in humans. Validation of these selected unique DEGs using real-time PCR demonstrated > absolute 2-fold changes in mRNA versus air controls, consistent with RNA-seq analysis. CONCLUSION: Cigarette smoke-induced COPD in ferrets modulates gene expression consistent with human COPD and suggests that the ferret model may be uniquely well suited for the study of aspects of the disease.

Stochastic exciton-scattering theory of optical line shapes: Renormalized many-body contributions.

Spectral line shapes provide a window into the local environment coupled to a quantum transition in the condensed phase. In this paper, we build upon a stochastic model to account for non-stationary background processes produced by broad-band pulsed laser stimulation, as distinguished from those for stationary phonon bath. In particular, we consider the contribution of pair-fluctuations arising from the full bosonic many-body Hamiltonian within a mean-field approximation, treating the coupling to the system as a stochastic noise term. Using the Itô transformation, we consider two limiting cases for our model, which lead to a connection between the observed spectral fluctuations and the spectral density of the environment. In the first case, we consider a Brownian environment and show that this produces spectral dynamics that relax to form dressed excitonic states and recover an Anderson-Kubo-like form for the spectral correlations. In the second case, we assume that the spectrum is Anderson-Kubo like and invert to determine the corresponding background. Using the Jensen inequality, we obtain an upper limit for the spectral density for the background. The results presented here provide the technical tools for applying the stochastic model to a broad range of problems.

Comparison of cost changes due to the COVID-19 pandemic for Dermatology residency applications in the USA.

We performed a cost estimation of dermatology residency applications prior to COVID-19 pandemic restrictions (2016-2020) and during the COVID-19 pandemic (2021) and surveyed dermatology programme directors to assess the impact of virtual interviews. We found that COVID-19 virtual interviews significantly reduced the cost of applications. We understand that the changes forced by the pandemic were challenging and not ideal; however, the online aspect of interviews provided a way for applicants to save a significant amount of money.

Can honey improve the quality of cryopreserved cross bred ram semen added to tris egg yolk extender?

BACKGROUND: Honey can improve the quality of cryopreserved ram semen because of its multinutrient and cryoprotective nature added to standard tris egg yolk extender. OBJECTIVE: Different concentrations of honey were added to the standard tris egg yolk extender to improve the post-thaw quality of crossbred ram semen. METHOD: Thirty six (36) ejaculates from eight healthy cross bred rams were pooled and divided into four aliquots. Standard tris egg yolk extender without any alteration acted as Control (C) and was supplemented with different concentrations of honey, viz. T1 (honey 1.5%), T2 (2.5%), and T3 (3.5%). RESULTS: The percent (mean ± S.E.M) sperm motility at pre-freeze was significantly (P < 0.05) higher in Group T2 and at post-thaw in Group T3 in comparison to T1 and C treatment groups. The percent (mean ± S.E.M) HOST reacted spermatozoa at post-thaw was significantly (P < 0.05) higher in Group C and at pre-freeze the value was significantly (P < 0.05) higher in the same treatment group than Group T1. The mean MDA level (mean ± S.E.M) at post thaw was significantly (P < 0.05) lower in Group T3 than the treatment groups C and Group T1. CONCLUSION: From this study it is concluded that the addition of 3.5% honey to the standard tris egg yolk extender provides better protection to ram semen than the addition of 1.5% honey (i.e., Control). doi.org/10.54680/fr22610110212.

Endoscopic findings among geriatric patients with anaemia and chronic kidney disease at a tertiary teaching hospital in Malaysia.

BACKGROUND: Older people with chronic kidney disease (CKD) may be anaemic due to various reasons, and they are vulnerable to various consequences. One of the most important causes of anaemia to be recognised in this population is gastrointestinal loss. The outcome can be improved by early detection, careful investigation, and suitable therapies. There is currently no standardised grading scale or reliable indicators to assist clinicians on handling gastrointestinal workup in elderly CKD patients who are anaemic. METHODS: A cross-sectional study of 171 people aged 60 and over who had CKD (stages 3-5), including those on Renal Replacement Therapy (RRT) and anaemia. Using oesophagogastroduodenoscopy, colonoscopy, and double balloon endoscopy, we analysed the endoscopic findings and calculated the prevalence of anaemia secondary to gastrointestinal disease. Haemoglobin, mean corpuscular volume (MCV), mean corpuscular haemoglobin concentration (MCHC), mean cell haemoglobin (MCH), iron panels, and immuno-faecal occult blood test (iFOBT) were evaluated to predict the diagnostic utility of each parameter in relation to gastrointestinal disorder in the elderly CKD population. RESULTS: Abnormal endoscopic findings were obtained by upper and lower endoscopy in 98 individuals (57.3%). Upper endoscopy revealed the most prevalent lesions to be gastritis, gastric ulcer, and duodenal ulcer. The upper and lower endoscopies revealed a total of 14.0% malignant and pre-malignant lesions. T-test and receiver-operating characteristic (ROC) curve were performed on all haematological parameters and iron panels. Low ferritin level (less than 100 ng/mL) and combination with low transferrin saturation (less than 20%) have a significant p value less than 0.05. None of these variables had a significant area under the curve (AUC) of more than 0.75. CONCLUSION: Positive endoscopic findings of anaemia are common in the older population at various stages of CKD, regardless of age, gender, or race. Malignant and premalignant lesions are not uncommon in older CKD patients. In the older CKD population, GI inflammation and ulceration are common lesions. Serum ferritin and TSAT levels are useful indicators of GI disorder in this population. Endoscopic evaluation as part of anaemia workup in the older people with CKD should not be ruled out.

Oral metronomic chemotherapy after definitive chemoradiation in esophageal squamous cell carcinoma: a randomized clinical trial.

BACKGROUND: Improving outcomes in locally advanced esophageal/GEJ squamous cell cancer (SCC) is an unmet need. We investigated the addition of oral metronomic chemotherapy (OMC) following definitive chemoradiotherapy (CRT). MATERIALS AND METHODS: This was a randomized open-label integrated phase II/III study in patients with SCC of esophagus/GEJ following definitive CRT who had no radiologic evidence of progression, and no endoscopically detected disease. Randomization was 1:1 to OMC (celecoxib 200 mg twice daily and methotrexate 15 mg/m2 weekly) for 12 months or observation. The primary endpoint for the phase II portion was progression-free survival (PFS); secondary endpoints were overall survival (OS) and toxicity. P ≤ 0.2 for PFS was required to proceed to phase III. RESULTS: Between Jan 2016 and Dec 2019, we enrolled 151 patients for the phase II portion, 75 to OMC and 76 to observation. The tumor originated in the upper thoracic esophagus in 79% patients. Concurrent CRT consisted of median 63 Gy in a median of 35 fractions; concurrent chemotherapy was weekly paclitaxel + carboplatin in 91%. OMC was started at a median of 2.6 months (IQR 2.3-2.8) from CRT completion. Grade 3 or higher toxicities occurred in 18 patients (24%) in the OMC arm and 9 (12%) in the observation arm; P = 0.071. Median PFS was 25 months (95% CI, 17-58) in the OMC arm and was not attained [NA] (95% CI, 25-NA) in the observation arm; HR, 1.51, 95% CI, 1-2; P = 0.073. Median OS was 36 months (95% CI, 23-NA) in the OMC arm, and not attained (95% CI, NA-NA) in the observation arm; HR, 1.77; 95% CI, 1-2.9; P = 0.023. CONCLUSION: Oral metronomic methotrexate and celecoxib in patients who have not progressed radiologically and have no endoscopic evidence of disease following radical CRT for locally advanced esophageal/GEJ SCC does not improve outcomes and may lower survival. [Funded by the TMC-Research Administration Council (TRAC); CHROME study (CHemoRadiotherapy followed by Oral Metronomic therapy in Esophageal cancer); ctri.nic.in number: CTRI/2015/09/006204]. TRIAL REGISTRATION NUMBER: CTRI/2015/09/006204.

Inhaled high molecular weight hyaluronan ameliorates respiratory failure in acute COPD exacerbation: a pilot study.

BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) carry significant morbidity and mortality. AECOPD treatment remains limited. High molecular weight hyaluronan (HMW-HA) is a glycosaminoglycan sugar, which is a physiological constituent of the lung extracellular matrix and has notable anti-inflammatory and hydrating properties. RESEARCH QUESTION: We hypothesized that inhaled HMW-HA will improve outcomes in AECOPD. METHODS: We conducted a single center, randomized, placebo-controlled, double-blind study to investigate the effect of inhaled HMW-HA in patients with severe AECOPD necessitating non-invasive positive-pressure ventilation (NIPPV). Primary endpoint was time until liberation from NIPPV. RESULTS: Out of 44 screened patients, 41 were included in the study (21 for placebo and 20 for HMW-HA). Patients treated with HMW-HA had significantly shorter duration of NIPPV. HMW-HA treated patients also had lower measured peak airway pressures on the ventilator and lower systemic inflammation markers after liberation from NIPPV. In vitro testing showed that HMW-HA significantly improved mucociliary transport in air-liquid interface cultures of primary bronchial cells from COPD patients and healthy primary cells exposed to cigarette smoke extract. INTERPRETATION: Inhaled HMW-HA shortens the duration of respiratory failure and need for non-invasive ventilation in patients with AECOPD. Beneficial effects of HMW-HA on mucociliary clearance and inflammation may account for some of the effects (NCT02674880, www.clinicaltrials.gov ).