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Purpose: Continuous-glucose-monitoring (CGM) sensors provide near-real-time glucose data and have been introduced commercially as a tool to inform nutrition decisions. The aim of this pilot study was to explore how factors such as the menstrual phase, extended running duration, and carbohydrates affect CGM outcomes among trained eumenorrheic females in an outdoor simulated ultraendurance running event. Methods: Twelve experienced female ultrarunners (age 39 [6] y) participated in this crossover study. Participants completed an ultraendurance simulation run of 4 hours in the midfollicular and midluteal phases of their menstrual cycle, which consisted of a 3-hour fasted outdoor run (FASTED) followed by a 1-hour treadmill run (TREAD), where 3 standardized 20-g oral glucose doses were provided. Results: Using a mixed linear model, the menstrual phase was statistically significant for differences in glucose measurements from CGM compared with capillary glucose sampling during TREAD (P =.02) but not FASTED. Additionally, the CGM sensor reported glucose levels with an average of −0.43 mmol·L−1 (95% CI, − 0.86 to −0.005) and −1.02 mmol·L−1 (95% CI, −1.63 to −0.42) lower in fasted and fed scenarios, respectively, when compared with capillary glucose. Conclusion: CGM underreports capillary glucose during fasted and fed exercise. Factors contributing to this underreporting between the sampling methods (CGM vs capillary) were dependent on a combination of exogenous glucose availability, individual biological differences, and the menstrual phase. [ABSTRACT FROM AUTHOR]

Interstitial lung disease (ILD) associated with rheumatoid arthritis or with connective tissue diseases such as systemic sclerosis can be collectively named systemic autoimmune rheumatic disease-associated ILDs (SARD-ILDs) or rheumatic musculoskeletal disorder-associated ILDs. SARD-ILDs result in substantial morbidity and mortality, and there is a high medical need for effective therapies that target both fibrotic and inflammatory pathways in SARD-ILD. Phosphodiesterase 4 (PDE4) hydrolyses cyclic AMP, which regulates multiple pathways involved in inflammatory processes. PDE4 is overexpressed in peripheral blood monocytes from patients with inflammatory diseases. However, clinical data on pan-PDE4 inhibition in fibrotic conditions are lacking. The PDE4B subtype is highly expressed in the brain, lungs, heart, skeletal muscle and immune cells. As such, inhibition of PDE4B may be a novel approach for fibrosing ILDs such as idiopathic pulmonary fibrosis (IPF) and SARD-ILD. Preclinical data for PDE4B inhibition have provided initial evidence of both anti-inflammatory and antifibrotic activity, with reduced potential for gastrointestinal toxicity compared with pan-PDE4 inhibitors. In a proof-of-concept phase II trial in patients with IPF, nerandomilast (BI 1015550), the only PDE4B inhibitor currently in clinical development, prevented a decline in lung function over 12 weeks compared with placebo. The potential clinical benefit of PDE4B inhibition is now being investigated in the phase III setting, with two trials evaluating nerandomilast in patients with IPF (FIBRONEER-IPF) or with progressive pulmonary fibrosis other than IPF (FIBRONEER-ILD). Here, we review the preclinical and clinical data that provide rationale for PDE4B inhibition as a treatment strategy in patients with SARD-ILD.

BackgroundAnti-MDA5 (Melanoma differentiation-associated protein-5) positive dermatomyositis (MDA5+-DM) is characterised by rapidly progressive interstitial lung disease (ILD) and high mortality. MDA5 is an RNA sensor and a key pattern recognition receptor for the SARS-CoV-2 virus.MethodsThis is a retrospective observational study of a surge in MDA5 autoimmunity, as determined using a 15 muscle-specific autoantibodies (MSAs) panel, between Janurary 2018 and December 2022 in Yorkshire, UK. MDA5-positivity was correlated with clinical features and outcome, and regional SARS-CoV-2 positivity and vaccination rates. Gene expression patterns in COVID-19 were compared with autoimmune lung disease and idiopathic pulmonary fibrosis (IPF) to gain clues into the genesis of the observed MDA5+-DM outbreak.FindingsSixty new anti-MDA5+, but not other MSAs surged between 2020 and 2022, increasing from 0.4% in 2019 to 2.1% (2020), 4.8% (2021) and 1.7% (2022). Few (8/60) had a prior history of confirmed COVID-19, peak rates overlapped with regional SARS-COV-2 community positivity rates in 2021, and 58% (35/60) had received anti-SARS-CoV-2 vaccines. 25/60 cases developed ILD which rapidly progression with death in 8 cases. Among the 35/60 non-ILD cases, 14 had myositis, 17 Raynaud phenomena and 10 had dermatomyositis spectrum rashes. Transcriptomic studies showed strong IFIH1 (gene encoding for MDA5) induction in COVID-19 and autoimmune-ILD, but not IPF, and IFIH1 strongly correlated with an IL-15-centric type-1 interferon response and an activated CD8+ T cell signature that is an immunologic hallmark of progressive ILD in the setting of systemic autoimmune rheumatic diseases. The IFIH1 rs1990760TT variant blunted such response.InterpretationA distinct pattern of MDA5-autoimmunity cases surged contemporaneously with circulation of the SARS-COV-2 virus during COVID-19. Bioinformatic insights suggest a shared immunopathology with known autoimmune lung disease mechanisms.FundingThis work was supported in part by the National Institute for Health Research (NIHR) Leeds Biomedical Research Centre (BRC), and in part by the National Institutes of Health (NIH) grant R01-AI155696 and pilot awards from the UC Office of the President (UCOP)-RGPO (R00RG2628, R00RG2642 and R01RG3780) to P.G. S.S was supported in part by R01-AI141630 (to P.G) and in part through funds from the American Association of Immunologists (AAI) Intersect Fellowship Program for Computational Scientists and Immunologists.

The study aims to conduct a meta-analysis on 5-year survival rate and mortality-related factors in the patients with primary Sjögren's syndrome concomitant with interstitial lung disease (pSS-ILD). Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we searched various platforms and databases until November 22, 2023. We used the Newcastle–Ottawa Scale (NOS) for quality assessment and extracted study characteristics and effect sizes. The pooled 5-year survival rate, hazard ratios (HRs), and the corresponding 95% confidence intervals (95% CIs) were then calculated. A p-value of less than 0.05 was considered statistically significant. Patients with pSS-ILD. Mortality in patients with pSS-ILD. Out of 188 articles, seven met the inclusion criteria. The meta-analysis estimated a 5-year survival rate of 82% (73%-91%). Mortality-related factors estimated by the meta-analysis included older age (HRs = 1.06, 95% CI 1.03–1.09, P < 0.0001), history of smoking (HRs = 3.44, 95% CI 2.14–5.53, P < 0.00001), anti-SSA antibody positivity (HRs = 0.41, 95% CI 0.20–0.85, P = 0.02), anti-SSB antibody positivity (HRs = 0.42, 95% CI 0.18–0.98, P = 0.04), reduced forced vital capacity (FVC; HRs = 0.96, 95% CI 0.95–0.98, P < 0.0001), reduced 6-min walk distance (6MWD; HRs = 0.99, 95% CI 0.99–1.00, P = 0.0008), presence of a reticular abnormality (HRs = 3.03, 95% CI 1.54–5.95, P = 0.001), and decreased arterial partial pressure of oxygen (PaO2) levels (HRs = 0.99, 95% CI 0.97–1.00, P = 0.04). The 5-year survival rate for pSS-ILD is 82%. Older age, history of smoking, anti-SSA antibody negativity, anti-SSB antibody negativity, reduced FVC, reduced 6MWD, presence of a reticular abnormality, and decreased PaO2 levels increase the mortality risk in pSS-ILD. [ABSTRACT FROM AUTHOR]

In the presented study first-principles pseudopotential method was used to investigate the formation energy of native point defects in the chalcogenide semiconductor CdGa2S4 compound. Defects such as interstitials of Cd, Ga, and antisites of Cd, Ga in their relevant charge states are considered and discussed. Additional acceptor and donor levels associated with defects that appeared in the band gap were analyzed using GGA + SG15 approximations. Transition levels were calculated for charge states and the behavior of the Fermi level was studied depending on the degree of charge states. Charge localization functions for every defect case were analyzed The presented results in this article provide the pioneer step for experimental study related to the defect formation energy in CdGa2S4 compound. [ABSTRACT FROM AUTHOR]

Background: Systemic lupus erythematosus (SLE) increases the risk of interstitial lung disease (ILD). SLE is also linked to an elevated risk of type 2 diabetes mellitus (T2DM). However, the impact of T2DM on ILD risk in patients with SLE is still unclear. This study aimed to compare the prevalence of ILD in patients with SLE based on the presence of T2DM (SLE + T2DM+) or its absence (SLE + T2DM−). Methods: This was a retrospective cohort study using the 2019–2020 National Inpatient Sample database. Adult SLE patients were identified and stratified by T2DM status. Comparable cohorts were created using propensity score matching, resulting in 10,532 patients in each cohort. Multivariate logistic regression assessed the association between T2DM and ILD. Results: T2DM was associated with a lower prevalence of ILD in patients with SLE (OR 0.798, 95% CI: 0.695–0.918, p =.002), occurring in 371 (3.5%) patients with T2DM compared to 463 (4.4%) patients without T2DM. Specifically, this difference was mainly driven by pulmonary fibrosis, which was significantly less frequent in the T2DM group (1.3% vs 1.8%, OR 0.7, 95% CI: 0.560–0.875, p =.002). No differences were found in secondary outcomes, including death rates, length of hospital stay, ARDS, pneumothorax, pleural effusion, or pulmonary arterial hypertension. Conclusion: Our study suggests that T2DM significantly reduced ILD risk in patients with SLE, specifically diminishing pulmonary fibrosis prevalence. Further research should explore mechanisms for this protective association between T2DM and ILD development in SLE. These findings may guide management strategies for this vulnerable population. [ABSTRACT FROM AUTHOR]

Schizorhynchia is a group of free-living interstitial flatworms within Kalyptorhynchia, characterized by possessing a split proboscis. To date, only seven species of Schizorhynchia have been recorded from Japan. Here, we describe two new species of schizorhynchs, Proschizorhynchella quadricaudata sp. nov. and Cheliplana izuensis sp. nov., based on specimens collected from the intertidal zone of Japanese waters. We also explored the phylogenetic position of the new taxa based on partial sequences of the nuclear 18S rRNA and 28S rRNA genes. Proschizorhynchella quadricaudata sp. nov. is characterized by (i) proboscis lips with a row of glands; (ii) a simple cone-shaped stylet; and (iii) a caudal end with four finger-shaped projections. Cheliplana izuensis sp. nov. can be distinguished from its congeners by (i) two strong hooks with bifurcate tips, encircling the distal part of the spiny cirrus; (ii) the fact that the proximal 20% of the cirrus length is unarmed; (iii) proboscis' sidepieces lacking needles; (iv) paired seminal vesicles; and (v) the presence of a vagina. The phylogenetic analyses support the position of P. quadricaudata sp. nov. within Schizorhynchidae and the position of C. izuensis sp. nov. in a clade containing all species of Cheliplana within Cheliplanidae. [ABSTRACT FROM AUTHOR]

Shortened telomere lengths (TLs) can be caused by single nucleotide polymorphisms and loss-of-function mutations in telomere-related genes (TRG), as well as ageing and lifestyle factors such as smoking. Our objective was to determine if shortened TL is associated with interstitial lung disease (ILD) in individuals with rheumatoid arthritis (RA). This is the largest study to demonstrate and replicate that shortened peripheral blood leukocytes-TL is associated with ILD in patients with RA compared with RA without ILD in a multinational cohort, and short PBL-TL was associated with baseline disease severity in RA-ILD as measured by forced vital capacity percent predicted.

Background: Interstitial lung disease (ILD) is a significant cause of morbidity and mortality in patients with systemic sclerosis (SSc). To date, clinical practice guidelines regarding treatment for patients with SSc-ILD are primarily consensus based. Methods: An international expert guideline committee composed of 24 individuals with expertise in rheumatology, SSc, pulmonology, ILD, or methodology, and with personal experience with SSc-ILD, discussed systematic reviews of the published evidence assessed using the Grading of Recommendations, Assessment, Development, and Evaluation approach. Predetermined conflict-of-interest management strategies were applied, and recommendations were made for or against specific treatment interventions exclusively by the nonconflicted panelists. The confidence in effect estimates, importance of outcomes studied, balance of desirable and undesirable consequences of treatment, cost, feasibility, acceptability of the intervention, and implications for health equity were all considered in making the recommendations. This was in accordance with the American Thoracic Society guideline development process, which is in compliance with the Institute of Medicine standards for trustworthy guidelines. Results: For treatment of patients with SSc-ILD, the committee: 1) recommends the use of mycophenolate; 2) recommends further research into the safety and efficacy of (a) pirfenidone and (b) the combination of pirfenidone plus mycophenolate; and 3) suggests the use of (a) cyclophosphamide, (b) rituximab, (c) tocilizumab, (d) nintedanib, and (e) the combination of nintedanib plus mycophenolate. Conclusions: The recommendations herein provide an evidence-based clinical practice guideline for the treatment of patients with SSc-ILD and are intended to serve as the basis for informed and shared decision making by clinicians and patients.

BackgroundPatients with multiple myeloma are immunosuppressed due to both the disease itself and immunosuppressive therapies. Thus, when presenting with respiratory failure and pulmonary opacities, pneumonia must be considered. However, while rare, immunomodulating medications used in the treatment of multiple myeloma can also cause potentially life-threatening respiratory failure, a distinction which has important treatment implications.Case presentationAn 80-year-old male with recently diagnosed multiple myeloma undergoing treatment with lenalidomide and daratumumab presented with acute, rapidly progressive hypoxic respiratory failure ultimately requiring intubation and mechanical ventilatory support. Imaging revealed bilateral pulmonary opacities, however infectious workup was negative, and he was ultimately diagnosed with lenalidomide-induced interstitial pneumonitis, a rare but serious adverse effect of this medication. He was treated with drug discontinuation and methylprednisolone, and quickly recovered.ConclusionLenalidomide is an immunomodulating medication used in the treatment of multiple myeloma, and is associated with rare but serious cases of drug-induced interstitial pneumonitis. Thus, if a patient receiving lenalidomide develops shortness of breath and/or hypoxia, drug-induced pneumonitis must be on the differential. Permanent drug discontinuation with or without corticosteroids is the mainstay of treatment, and patients are often able to fully recover, underscoring the need for early recognition of this condition.

Cutaneous granulomatous reactions are diverse, both from the clinical and the pathological perspective. Most underlying pathophysiological aspects remain elusive. Interstitial granulomatous dermatitis and palisaded neutrophilic and granulomatous dermatitis have been claimed to be reactions to systemic disorders, such as infectious, inflammatory, or neoplastic conditions. Recently, the overarching term "reactive granulomatous dermatitis" has been coined to unify both entities. We herein report two cases of reactive granulomatous dermatitis presenting with the widely known, albeit infrequent "rope sign" and provide clinicopathological correlation. The two patients included a 53-year-old woman with enlarging erythematous plaques and underlying palpable cords on both sides of trunk near axillae (rope sign), and a 51-year-old woman with personal history of rheumatoid arthritis and a palpable cord on the left aspect of the trunk. Pathological findings were compatible with reactive granulomatous dermatitis in both cases. In conclusion, the rope sign represents a strikingly infrequent but decisive diagnostic clue of reactive granulomatous dermatitis.

Aging and cellular senescence are increasingly recognized as key contributors to pulmonary fibrosis. However, our understanding in the context of scleroderma-associated interstitial lung disease (SSc-ILD) is limited. To investigate, we leveraged previously established lung aging- and cell-specific senescence signatures to determine their presence and potential relevance to SSc-ILD. We performed a gene expression meta-analysis of lung tissues from 38 SSc-ILD and 18 healthy controls and found that markers (GDF15, COMP, and CDKN2A) and pathways (p53) of senescence were significantly increased in SSc-ILD. When probing the established aging and cellular senescence signatures, we found that epithelial and fibroblast senescence signatures had a 3.6- and 3.7-fold enrichment, respectively, in the lung tissue of SSc-ILD and that lung aging genes (CDKN2A, FRZB, PDE1A, and NAPI12) were increased in SSc-ILD. These signatures were also enriched in SSc skin and associated with degree of skin involvement (limited vs. diffuse cutaneous). To further support these findings, we examined telomere length (TL), a surrogate for aging, in the lung tissue and found that, independent of age, SSc-ILD had significantly shorter telomeres than controls in type II alveolar cells in the lung. TL in SSc-ILD was comparable to idiopathic pulmonary fibrosis, a disease of known aberrant aging. Taken together, this study provides novel insight into the possible mechanistic effects of accelerated aging and aberrant cellular senescence in SSc-ILD pathogenesis.

OBJECTIVE: To assess adverse events (AEs) in relation to baseline body mass index (BMI) and the risk of malnutrition in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) treated with nintedanib. METHODS: Among patients with SSc-ILD randomized to receive nintedanib or placebo in the SENSCIS trial, we assessed AEs in subgroups by baseline BMI ≤20 kg/m2 and BMI >20 kg/m2 , and the risk of malnutrition using a modified version of the Malnutrition Universal Screening Tool (MUST), over 52 weeks. RESULTS: The AE profile of nintedanib was similar between subgroups with a baseline BMI ≤20 kg/m2 (n = 61) and a baseline BMI >20 kg/m2 (n = 515). In these subgroups, respectively, AEs led to treatment discontinuation in 16.7% and 15.9% of the nintedanib group and 13.5% and 8.0% of the placebo group, respectively. Based on the modified MUST, the proportions of patients who had a low risk of malnutrition at baseline and at their last assessment were 74.0% in the nintedanib group and 78.1% in the placebo group, while the proportions who were classified as at low risk at baseline but at high risk by their last assessment were 4.5% in the nintedanib group and 1.0% in the placebo group. CONCLUSION: In the SENSCIS trial, most patients with SSc-ILD remained at low risk of malnutrition over 52 weeks, but the proportion at high risk was higher in patients who received treatment with nintedanib compared to those who received placebo. Management of disease manifestations and AEs that may be associated with weight loss is important to reduce the risk of malnutrition in patients with SSc-ILD.

The purpose of this work was to evaluate whether inter-fraction imaging and replanning enhance treatment delivery adherence to clinical planning objectives in the context of a 5-fraction template-based interstitial brachytherapy (TISB) approach for gynecologic cancer treatment. This retrospective study analyzed nineteen patients who underwent 5 fractions of interstitial brachytherapy over 3 days using the Syed–Neblett template. A verification CT scan was acquired for applicator assessment and reviewed by a radiation oncologist and medical physicist before each fraction. Eleven patients required replanning at least once during the treatment course. Replanning on the verification CT scan consisted of generating new target and organ-at-risk contours, digitizing catheter positions, and optimizing source dwell times to meet planning objectives. Dwell times and positions from the initial treatment plan were evaluated on the new contours to assess the dose that would have been delivered without replanning (nonadapted). Significance of nonadapted versus adapted dose differences were evaluated using a 2-sided Wilcoxon sum rank test. The average (min, max) change in dose (Gy) between the clinically delivered plans and the nonadapted plans were HR-CTV D 90% : −6.5 (−0.6, −15.1), HR-CTV D 98% : −6.5 (−0.4, −12.6), Bladder D 2cc : −0.5 (0.0, −2.8), Bowel D 2cc : −0.8 (0.0, −3.2), Rectum D 2cc : −1.1 (0.0, −11.5), Sigmoid D 2cc : −1.4 (−0.1, −5.4). Dosimetric changes in HR-CTV coverage were significantly improved with replanning while organ-at-risk differences were nonsignificant (p > 0.05). Fraction 3 was the most common fraction indicated for replanning. Replanning template-based interstitial brachytherapy can improve target coverage and adherence to planning goals. [ABSTRACT FROM AUTHOR]

Background: Many patients with chronic obstructive pulmonary disease and fibrotic interstitial lung disease suffer from severe dyspnea and reduced quality of life, despite receiving optimal disease-modifying treatment for their illness. Studies have suggested that these patients may benefit from treatment with low-dose opioids. However, many patients decline opioid treatment. This has led to patients not receiving proper palliative treatment of their lung disease. Aim: To identify potential barriers that prevent patients from receiving adequate palliative care with opioids and enable doctors to address patients' concerns. Design: A qualitative study based on semi-structured interviews. Interviews were transcribed and thematic analysis was done using NVivo. Setting/Participants: Patients were recruited when scheduled for out-patient follow-up at Center for Rare Lung Diseases or at the COPD clinic, Aarhus University Hospital. Eligible patients were 18 years of age, did not currently receive opioids or had ever received opioids for dyspnea. Results: A total of 28 patients participated. One patient was excluded before final analysis of 27 patients. Four themes were identified: Fear of side-effects, Need for more information, Stigma of opioids association with severe illness and dying, and No discernible barriers. Furthermore, three sub-themes to Fear of side-effects were identified: Fear of addiction, concern for sedative effect, and fear for loss of mobility due to inability to drive a car. The most expressed concern was Fear of side-effects, especially addiction. Conclusions: Pre-conceived notions about opioids prevent some patients with chronic obstructive lung disease or interstitial lung disease from receiving palliative care for breathlessness. [ABSTRACT FROM AUTHOR]

Introduction: Bladder pain syndrome/interstitial cystitis (BPS/IC) is characterized by repeated pain, pressure, or discomfort in the bladder and pelvic area, and presents both diagnostic and therapeutic challenges for clinicians and researchers because of its enigmatic and poorly comprehended nature. The purpose of this study was to identify the prevalence of bladder pain syndrome/interstitial cystitis in a tertiary care center in the Central region of Saudi Arabia. Methodology of the study: The study shall be a cross-sectional survey conducted at King Khalid Hospital, Majmaah, Saudia Arabia from May 2021 to April 2024. A total of 800 patients were studied, which included females aged 18 years and above. Data collection was based on patient questionnaires plus some clinical evaluations. The Interstitial Cystitis Symptom Index (ICSI) questionnaire, a validated and widely used tool, was used to assess symptoms associated with Bladder Pain Syndrome/Interstitial Cystitis (BPS/IC). Results: A significant majority, 57.6%, reported never experiencing a sudden urge to urinate, while 14.1% felt this urge almost always. Regarding frequent urination, 27.6% of the participants never had to urinate within two hours of their last visit, but for 13.9%, this happened almost always. Bladder pain or pressure caused no problems for 62.6% of the respondents, while 11.9% reported this as a moderate problem, and 7.0% thought it was a big problem. The most common comorbidities were anxiety and depression, each affecting 23.4% of participants, reflecting a significant overlap between psychological distress and BPS/IC. Conclusion: It was noted that among patients with BPS/IC, quality of life was greatly affected, symptom severity was highly variable, and there was a high prevalence of associated comorbidities of anxiety, depression, and BPS. [ABSTRACT FROM AUTHOR]

Mesopsammic polyclad members in the family Boniniidae have attracted attention in terms of their evolutionary shifts of microhabitat and their unique morphology such as a pair of pointed tentacles extending from the anterolateral margins and prostatoid organs harbouring stylets. Here, we establish a new species of this family as Boninia panamensis sp. nov. from the Pacific coasts of Panama, based on its morphological characteristics of (i) four cerebral and 61–80 marginal eyespots, (ii) two prostatoid organs located anterior and posterior to the penis papilla, and (iii) two uterine canals departing from the anterior part of the Lang's vesicle. We also report Boninia cf. uru from Hawai'i, USA, based on its morphological identity with B. uru from Okinawa, Japan, along with their genetic distances for the partial cytochrome c oxidase subunit I (COI) sequences, which were beyond the range of intraspecific differences observed in congeners in this study. Boninia oaxaquensis is also reported from Panama as a new locality for the species. Involving the above-mentioned three species sequenced herein, we reconstructed molecular phylogenetic trees of Boninia based on the four gene markers (18S rDNA, 28S rDNA, 16S rDNA and COI). Our phylogenetic trees indicated the synapomorphy within the genus Boninia of the small numbers of stylets (2–4) and the connection route of the uterine canals to the Lang's vesicle. The results also showed a characteristic distribution pattern in which pairs of species in distinct lineages occurred sympatrically with different microhabitats, as observed in Boninia uru and Boninia yambarensis in Okinawa and B. panamensis sp. nov. and B. oaxaquensis in Panama. In addition, we discuss possible speciation pathways in this genus based on the tree topology. ZooBank: Boniniidae is a family of marine polyclad flatworms harbouring nine named species distributed worldwide. We describe a new boniniid species, Boninia panamensis from the Pacific coasts of Panama based on morphological and molecular data. We also report Boninia cf. uru from Hawai'i and Boninia oaxaquensis from Panama along with morphological descriptions. In addition, we discuss synapomorphic traits and possible speciation pathways in this genus based on the reconstructed molecular phylogenetic results using 18S rDNA, 28S rDNA, 16S rDNA and COI. (Photograph by Marco Curini-Galletti.) [ABSTRACT FROM AUTHOR]

Background/Aim. Interstitial cystitis (IC)/bladder pain syndrome (BPS) is a condition with recurring discomfort or pain in the urinary bladder and the surrounding pelvic region without an identifiable disease. The aim of this study was to assess hydrodistension as a diagnostic and treatment procedure in patients with BPS. Methods. This prospective study included 45 patients who underwent cystoscopy with hydrodistension. The m ean v alues f or 2 4-hr voiding frequency, maximal voided urine volume, average voided urine volume, and minimal voided urine volume originated from the frequency volume chart. The values were compared between the time before hydrodistension and one, three, and six months after that. Results. By comparing the initial data and data in all three follow-up periods (after one, three, and six months), the statistical significance (p < 0.046) was found, and that: for 24-hr voiding frequency, it was 19.64 ± 3.56, 9.42 ± 1.71, 9.58 ± 1.45, and 12.2 ± 2.79, respectively; then, for the minimal voided urine volume (p < 0.03), it was 59.11 ± 23.72 mL, 114.89 ± 4.09 mL, 112.44 ± 100.86 mL, and 89.00 ± 29.45 mL, respectively; for an average voided volume (p < 0.04), it was 105.33 ± 18.29 mL, 186.89 ± 23.14 mL, 186.44 ± 21.44 mL, and 155.78 ± 30.78 mL, respectively. There was no significant statistical difference (p < 0.1) regarding the maximal voided urine volume between initial and follow-up interval data: 196.89 ± 43.68 mL, 312.89 ± 54.59 mL, 316.00 ± 49.47 mL, 266.67 ± 53.17 mL, respectively. Conclusion. Our results demonstrate that hydrodistension is a reliable diagnostic and therapeutic procedure. [ABSTRACT FROM AUTHOR]

Ectopic pregnancies are one of the most common causes of obstetric mortality worldwide. Interstitial ectopic pregnancies, defined as an extracavitary pregnancy within the portion of the Fallopian tube that transverses the myometrium, have reported mortality rates approximately seven times higher than all types of ectopic pregnancy combined. In contrast, intracavitary eccentric gestations, often labeled as "cornual" or "angular" pregnancies, have reportedly high rates of live birth. Unfortunately, the terms "interstitial," "cornual," and "angular" have long been used with varying diagnostic criteria and often interchangeably to describe a pregnancy near the uterotubal junction. The inconsistency in nomenclature and lack of clear diagnostic criteria to distinguish among these pregnancies has resulted in a paucity of data to provide accurate prognostic information and guide appropriate management. This review article aims to provide historical context for the terms "interstitial," "cornual," and "angular;" discuss previous and more recent innovations of diagnostic methods; and provide recommendations for concise terminology and inform management. [ABSTRACT FROM AUTHOR]

We aim to investigate perioperative and subacute postoperative complications in patients undergoing LDR or HDR monotherapy for prostate cancer. We hypothesize a low rate of complications, and a favorable toxicity profile in patients treated with HDR compared to LDR. A prospectively collected institutional database was queried for patients treated with HDR or LDR prostate monotherapy between 1998 and 2021. Toxicities were determined per CTCAE. Claims based billing codes were obtained to identify additional events. Events occurring within 4 months of treatment were defined as perioperative or subacute postoperative complications. 759 patients were identified, 446 received LDR with 125I, and 313 received HDR with 192Ir. HDR patients had higher risk features: 75.7% with Gleason score 7+ versus 2.4% of LDR, and 16% with initial PSA 10+ ng/mL versus 2.7% of LDR. Toxicities were mild with the most common being grade 1 GU frequency and nocturia at ∼50%. HDR patients had significantly less grade 2 dysuria (2.6% vs. 9.0%), frequency (4.8% vs. 9.4%), hematuria (1.0% vs. 5.2%), nocturia (3.8% vs. 9.4%), and urinary obstructive symptoms (7.3% vs. 11.2%), all statistically significant. 11 (1.4%) patients had infection requiring antibiotics: 8 (1.8%) from the LDR group and 3 (1%) from the HDR group. Cardiopulmonary events were low at <2% overall, without difference between HDR and LDR. Overall toxicity rates support the safety of prostate brachytherapy. HDR monotherapy is associated with significantly less perioperative and subacute postoperative GU events when compared to LDR monotherapy. Cardiopulmonary events were equally rare in both groups. [ABSTRACT FROM AUTHOR]

A new species of meiobenthic sipunculan, Phascolion kamchatikus sp. nov. collected from coarse sand and shell hash in shallow waters in the northwestern Pacific, is described and illustrated using light and electron microscopy. This new species is well distinguished from all other congeners by a unique combination of main taxonomic characters. This is the only sipunculan having only two primary tentacles in both juvenile and sexually mature worms. There are no hooks and holdfast papillae in the adult stages. Because of the presence of three nearly equal in size retractor muscles forming a retractor column divided for most of its length, this species is assigned to the subgenus Isomya of the genus Phascolion. Unlike most other species of the genus Phascolion , P. kamchatikus sp. nov. has an interstitial mode of life moving among the coarse sand grains and shell hash accumulated between rocks and stones in shallow water areas alongside the Pacific coast of Kamchatka, Aleutian Islands and Alaska Peninsula. Phascolion kamchatikus sp. nov. constitutes the only third interstitial species of the phylum Sipuncula. This is also the ninth species of Phascolion in the northwestern Pacific and the first interstitial representative of this genus in the Pacific Ocean. [ABSTRACT FROM AUTHOR]

Presented is an approach to a chest radiograph, paying particular attention to features commonly seen in the intensive care unit (ICU) with regards to iatrogenic lines and tubes, together with common pathologies that may be encountered. This is accompanied by helpful images to use as an aide memoire when reviewing ICU chest X-rays. Pitfalls in interpreting these often complex X-rays are also discussed. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of the study was to analyze patients with vaginal-involving recurrences of gynecological tumors and primary vaginal tumors, treated with transperineal interstitial brachytherapy (P-ISBT). Dosimetric, clinical, and toxicity analysis of these patients was conducted, incorporating MRI in volume definition and dose-volume dosimetry. Material and methods: Forty-two patients were retrospectively analyzed. They were treated with radical or adjuvant intent (in hysterectomized patients with high-risk of relapse). P-ISBT was performed with MUPIT (CT-based planning) in 18 patients (42.9%) and with Template Benidorm (TB) (MRI-based planning) in 24 patients (57.1%). Results: Median age was 59 years (range, 39-78 years). Median clinical target volume (CTV) was 81.4 cc (range, 33.8-286.2 cc) in MUPIT, and 47.5 cc (range, 10-156.4 cc) in TB-treated patients (p = 0.01). Median EQD2 for EBRT and brachytherapy D90 CTV was 69.2 Gy (range, 27.9-88.8 Gy) in MUPIT, and 77.2 Gy (range, 31-84.3 Gy) in TB. Median rectal D2cc was 69.2 Gy (range, 23.5-82.6 Gy) in MUPIT, and 66.3 Gy (range, 16.4-75 Gy) in TB. Median bladder D2cc was 71.5 Gy (range, 23.6-90.8 Gy) in MUPIT, and 66.9 Gy (range, 18.2-78.3 Gy) in TB. Median follow-up was 36.5 months (range, 4-188 months). Local control was 95% at 3 and 5 years. Overall survival was 77% at 3 years, and 66% at 5 years. Disease-specific survival was 81% at 3 years, and 75% at 5 years. Chronic grade 1-2 proctitis presented in 10 patients (24%; 8 treated with MUPIT and 2 treated with TB; p = 0.01). Grade 3 toxicity was documented in 4 patients (9.6%). Conclusions: MRI-based planning is superior to CT-based planning in P-ISBT. It allows for better definition of CTV, resulting in smaller and more selective treatment volumes. Our results show a tendency towards higher D90 CTV dose and lower rectal/bladder D2cc dose, leading to less events of late rectal toxicity. [ABSTRACT FROM AUTHOR]

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OBJECTIVES: To investigate computer-aided quantitative scores from high-resolution CT (HRCT) images and determine their longitudinal changes and clinical significance in patients with idiopathic inflammatory myopathies (IIMs)-related interstitial lung disease (IIMs-ILD). METHODS: The clinical data and HRCT images of 80 patients with IIMs who underwent serial HRCT scans at least twice were retrospectively analysed. Quantitative ILD (QILD) scores (%) were calculated as the sum of the extent of lung fibrosis, ground-glass opacity, and honeycombing. The individual time-estimated ΔQILD between two consecutive scans was derived using a linear approximation of yearly changes. RESULTS: The baseline median QILD (interquartile range) scores in the whole lung were 28.1% (19.1-43.8). The QILD was significantly correlated with forced vital capacity (r = -0.349, P = 0.002) and diffusing capacity for carbon monoxide (r = -0.381, P = 0.001). For ΔQILD between the first two scans, according to the visual ILD subtype, QILD aggravation was more frequent in patients with usual interstitial pneumonia (UIP) than non-UIP (80.0% vs 44.4%, P = 0.013). Multivariable logistic regression analyses identified UIP was significantly related to radiographic ILD progression (ΔQILD >2%, P = 0.015). Patients with higher baseline QILD scores (>28.1%) had a higher risk of lung transplantation or death (P = 0.015). In the analysis of three serial HRCT scans (n = 41), dynamic ΔQILD with four distinct patterns (improving, worsening, convex and concave) was observed. CONCLUSION: QILD changes in IIMs-ILD were dynamic, and baseline UIP patterns seemed to be related to a longitudinal progression in QILD. These may be potential imaging biomarkers for lung function, changes in ILD severity and prognosis in IIMs-ILD.

COPA syndrome is a recently described autosomal dominant inborn error of immunity characterized by high titer autoantibodies and interstitial lung disease, with many individuals also having arthritis and nephritis. Onset is usually in early childhood, with unique disease features including alveolar hemorrhage, which can be insidious, pulmonary cyst formation, and progressive pulmonary fibrosis in nonspecific interstitial pneumonia or lymphocytic interstitial pneumonia patterns. This review explores the clinical presentation, genetics, molecular mechanisms, organ manifestations, and treatment approaches for COPA syndrome, and presents a diagnostic framework of suggested indications for patient testing.

BackgroundStudies suggest a harmful pharmacogenomic interaction exists between short leukocyte telomere length (LTL) and immunosuppressants in idiopathic pulmonary fibrosis (IPF). It remains unknown if a similar interaction exists in non-IPF interstitial lung disease (ILD).MethodsA retrospective, multicentre cohort analysis was performed in fibrotic hypersensitivity pneumonitis (fHP), unclassifiable ILD (uILD) and connective tissue disease (CTD)-ILD patients from five centres. LTL was measured by quantitative PCR for discovery and replication cohorts and expressed as age-adjusted percentiles of normal. Inverse probability of treatment weights based on propensity scores were used to assess the association between mycophenolate or azathioprine exposure and age-adjusted LTL on 2-year transplant-free survival using weighted Cox proportional hazards regression incorporating time-dependent immunosuppressant exposure.ResultsThe discovery and replication cohorts included 613 and 325 patients, respectively. In total, 40% of patients were exposed to immunosuppression and 22% had LTL

BACKGROUND: Interstitial lung disease (ILD) is the most common cause of death in patients with systemic sclerosis (SSc). Prognostic biomarkers are needed to identify SSc-ILD patients at risk for progressive pulmonary fibrosis. This study investigates autoantibodies measured in bronchoalveolar lavage (BAL) fluid and in serum in reference to the clinical disease course of SSc-ILD. METHODS: Fifteen patients with new onset SSc-ILD underwent bronchoscopy. Autoantibody levels were analyzed using addressable laser bead immunoassay from BAL fluid and the serum. In a separate longitudinal cohort of 43 patients with early SSc-ILD, autoantibodies in serum were measured at baseline and pulmonary function tests were performed at least 2 times over the course of at least 2 or more years. Linear mixed effect models were created to investigate the relationship between specific autoantibodies and progression of SSc-ILD. Finally, lung tissue from healthy controls and from subjects with SSc was analyzed for the presence of the Ro52 antigen using immunohistochemistry. RESULTS: Among SSc-ILD patients who were positive for anti-Ro52 (N = 5), 3 (60%) had enrichment of anti-Ro52 in BAL fluid at a ratio exceeding 50x. In the longitudinal cohort, 10/43 patients (23%) were anti-Ro52 positive and 16/43 (37%) were anti-scl-70 positive. Presence of anti-Scl-70 was associated with a lower vital capacity (VC) at baseline (-12.6% predicted VC [%pVC]; 95%CI: -25.0, -0.29; p = 0.045), but was not significantly associated with loss of lung function over time (-1.07%pVC/year; 95%CI: -2.86, 0.71; p = 0.230). The presence of anti-Ro52 was significantly associated with the loss of lung function over time (-2.41%pVC/year; 95% CI: -4.28, -0.54; p = 0.013). Rate of loss of lung function increased linearly with increasing anti-Ro52 antibody levels (-0.03%pVC per arbitrary units/mL and year; 95%CI: -0.05, -0.02; p

OBJECTIVE: To investigate whether symptoms of gastroesophageal reflux disease and radiographic measures of esophageal dilation are associated with radiographic progression of systemic sclerosis-related interstitial lung disease (SSc-ILD). METHODS: Participants of the Scleroderma Lung Study II, which compared mycophenolate versus cyclophosphamide for SSc-ILD, completed the reflux domain of the University of California Los Angeles Scleroderma Clinical Trials Consortium Gastrointestinal Tract 2.0 at baseline. The diameter and area of the esophagus in the region of maximum dilation was measured by quantitative image analysis. Univariate and multivariable linear regression analyses were created to evaluate the relationship between these measures of esophageal involvement and progression of SSc-ILD over 2 years, based on the radiologic quantitative interstitial lung disease (QILD) and quantitative lung fibrosis (QLF) in the lobe of maximum involvement (LM). All multivariable models controlled for the treatment arm, baseline ILD severity, and proton-pump inhibitor use. RESULTS: The baseline mean patient-reported reflux score was 0.57, indicating moderate reflux (n = 141). Baseline mean maximal esophageal diameter and area were 22 mm and 242 mm2 , respectively. Baseline reflux scores were significantly associated with the change in QLF-LM and QILD-LM in the univariate and multivariable models. Neither radiographic measure of esophageal dilation was associated with the change in radiographic measures of lung involvement. CONCLUSION: Severity of reflux symptoms as measured by an SSc-specific questionnaire was independently associated with the change in the radiographic extent of ILD and fibrosis over 2 years in patients with SSc-ILD. Two objective measures of esophageal dilation were not associated with radiographic progression of ILD, highlighting the need for improved objective measures of esophageal dysfunction in SSc.

Trastuzumab deruxtecan (T-DXd) is an antibody drug conjugate with a topoisomerase I payload that targets the human epidermal growth factor receptor 2 (HER2). T-DXd is approved for patients with previously treated HER2-positive or HER2-low (immunohistochemistry [IHC] 1+ or IHC 2+/ISH-) metastatic/unresectable breast cancer (BC). In a second-line HER2-positive metastatic BC (mBC) population (DESTINY-Breast03 [ClinicalTrials.gov identifier: NCT03529110]), T-DXd demonstrated significantly improved progression-free survival (PFS) over ado-trastuzumab emtansine (12-month rate: 75.8% v 34.1%; hazard ratio, 0.28; P < .001), and in patients with HER2-low mBC treated with one prior line of chemotherapy (DESTINY-Breast04 [ClinicalTrials.gov identifier: NCT03734029]), T-DXd demonstrated significantly longer PFS and overall survival than physicians choice chemotherapy (10.1 v 5.4 months; hazard ratio, 0.51; P < .001, and 23.4 v 16.8 months; hazard ratio, 0.64; P < .001, respectively).Interstitial lung disease (ILD) is an umbrella term used for a group of diseases characterized by lung injury including pneumonitis, which can lead to irreversible lung fibrosis. ILD is a well-described adverse event associated with certain anticancer therapies, including T-DXd. An important part of T-DXd therapy for mBC consists of monitoring for and managing ILD. Although information on ILD management strategies is included in the prescribing information, additional information on patient selection, monitoring, and treatment can be beneficial in routine clinical practice. The objective of this review is to describe real-world, multidisciplinary clinical practices and institutional protocols used for patient selection/screening, monitoring, and management related to T-DXd-associated ILD.

PurposeSymptom heterogeneity in interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome, collectively termed urological chronic pelvic pain syndrome, has resulted in difficulty in defining appropriate clinical trial endpoints. We determine clinically important differences for 2 primary symptom measures, pelvic pain severity and urinary symptom severity, and evaluate subgroup differences.Materials and methodsThe Multidisciplinary Approach to the Study of Chronic Pelvic Pain Symptom Patterns Study enrolled individuals with urological chronic pelvic pain syndrome. We defined clinically important differences by associating changes in pelvic pain severity and urinary symptom severity over 3 to 6 months with marked improvement on a global response assessment using regression and receiver operating characteristic curves. We evaluated clinically important differences for absolute and percent change and examined differences in clinically important differences by sex-diagnosis, presence of Hunner lesions, pain type, pain widespreadness, and baseline symptom severity.ResultsAn absolute change of -4 was clinically important in pelvic pain severity among all patients, but clinically important difference estimates differed by pain type, presence of Hunner lesions, and baseline severity. Pelvic pain severity clinically important difference estimates for percent change were more consistent across subgroups and ranged from 30% to 57%. The absolute change urinary symptom severity clinically important difference was -3 for female participants and -2 for male participants with chronic prostatitis/chronic pelvic pain syndrome only. Patients with greater baseline severity required larger decreases in symptoms to feel improved. Estimated clinically important differences had lower accuracy among participants with low baseline symptoms.ConclusionsA reduction of 30%-50% in pelvic pain severity is a clinically meaningful endpoint for future therapeutic trials in urological chronic pelvic pain syndrome. Urinary symptom severity clinically important differences are more appropriately defined separately for male and female participants.

BackgroundThe MUC5B promoter variant (rs35705950) and telomere length are linked to pulmonary fibrosis and CT-based qualitative assessments of interstitial abnormalities, but their associations with longitudinal quantitative changes of the lung interstitium among community-dwelling adults are unknown.MethodsWe used data from participants in the Multi-Ethnic Study of Atherosclerosis with high-attenuation areas (HAAs, Examinations 1-6 (2000-2018)) and MUC5B genotype (n=4552) and telomere length (n=4488) assessments. HAA was defined as the per cent of imaged lung with attenuation of -600 to -250 Hounsfield units. We used linear mixed-effects models to examine associations of MUC5B risk allele (T) and telomere length with longitudinal changes in HAAs. Joint models were used to examine associations of longitudinal changes in HAAs with death and interstitial lung disease (ILD).ResultsThe MUC5B risk allele (T) was associated with an absolute change in HAAs of 2.60% (95% CI 0.36% to 4.86%) per 10 years overall. This association was stronger among those with a telomere length below an age-adjusted percentile of 5% (p value for interaction=0.008). A 1% increase in HAAs per year was associated with 7% increase in mortality risk (rate ratio (RR)=1.07, 95% CI 1.02 to 1.12) for overall death and 34% increase in ILD (RR=1.34, 95% CI 1.20 to 1.50). Longer baseline telomere length was cross-sectionally associated with less HAAs from baseline scans, but not with longitudinal changes in HAAs.ConclusionsLongitudinal increases in HAAs were associated with the MUC5B risk allele and a higher risk of death and ILD.

Abstract Background Interstitial lung disease (ILD) is an increasingly recognized complication of rheumatoid arthritis (RA) and is associated with significant morbidity and mortality. Many risk factors for RA-related ILD were reported. The current study aims to explore the features and risk factors of Saudi patients with RA-ILD. Methods This is a multicenter, retrospective, observational study of patients with RA-ILD. Clinical and radiological data from patients with RA-ILD were obtained from electronic medical records, including demographics, clinical characteristics, laboratory tests, pulmonary function tests, ECHO, and HRCT images. Result Out of 732 patients, 57 had RA-ILD. The mean age at the time of ILD diagnosis was 61.9 (± 12.2) years. RA-ILD diagnosis was significantly less among females (p = 0.008). Patients who ever smoked had significantly more RA-ILD (p 0.05). The most common symptoms of RA-ILD were cough (55.6%) and dyspnea (30.2%), and the most common ILD pattern was Non-specific Interstitial Pneumonia (NSIP) (55.6%) followed by Usual Interstitial Pneumonia (UIP) (38.9%). Traction bronchiectasis (75.5%) and glass ground opacities (73.6%) were also observed. The mean FVC and DLCO at baseline were 64.6% and 53.3%, respectively. Conclusion In this cohort of patients, Saudi RA-ILD patients had a predominant NSIP pattern conversely to what is seen globally. These findings could be explained by the lower rates of smoking in our patient population. Future prospective national studies are needed to confirm the current findings and better evaluate RA-ILD epidemiology and risk factors.

Atypical radiologic and clinical patterns may be observed within subgroups of lung adenocarcinoma. A 74-year-old man with progressive dyspnea and productive cough unresponsive to antibiotherapy showed bilateral interstitial changes in the lung parenchyma on computed tomography. We here report a patient followed up with a prediagnosis of interstitial lung disease but eventually diagnosed with lung adenocarcinoma following transthoracic lung biopsy.

Systemic sclerosis is a rare connective tissue disease; and interstitial lung disease (SSc-ILD) is associated with significant morbidity and mortality. There are no clinical, radiologic features, nor biomarkers that identify the specific time when patients are at risk for progression at which the benefits from treatment outweigh the risks. Our study aimed to identify blood protein biomarkers associated with progression of interstitial lung disease in patients with SSc-ILD using an unbiased, high-throughput approach. We classified SSc-ILD as progressive or stable based on change in forced vital capacity over 12 months or less. We profiled serum proteins by quantitative mass spectrometry and analyzed the association between protein levels and progression of SSc-ILD via logistic regression. The proteins associated with at a p value of

OBJECTIVES: To establish a framework by which experts define disease subsets in systemic sclerosis associated interstitial lung disease (SSc-ILD). METHODS: A conceptual framework for subclinical, clinical and progressive ILD was provided to 83 experts, asking them to use the framework and classify actual SSc-ILD patients. Each patient profile was designed to be classified by at least four experts in terms of severity and risk of progression at baseline; progression was based on 1-year follow-up data. A consensus was reached if ≥75% of experts agreed. Experts provided information on which items were important in determining classification. RESULTS: Forty-four experts (53%) completed the survey. Consensus was achieved on the dimensions of severity (75%, 60 of 80 profiles), risk of progression (71%, 57 of 80 profiles) and progressive ILD (60%, 24 of 40 profiles). For profiles achieving consensus, most were classified as clinical ILD (92%), low risk (54%) and stable (71%). Severity and disease progression overlapped in terms of framework items that were most influential in classifying patients (forced vital capacity, extent of lung involvement on high resolution chest CT [HRCT]); risk of progression was influenced primarily by disease duration. CONCLUSIONS: Using our proposed conceptual framework, international experts were able to achieve a consensus on classifying SSc-ILD patients along the dimensions of disease severity, risk of progression and progression over time. Experts rely on similar items when classifying disease severity and progression: a combination of spirometry and gas exchange and quantitative HRCT.

In a patient with interstitial lung disease (ILD) of known or unknown etiology other than idiopathic pulmonary fibrosis (IPF), progressive pulmonary fibrosis (PPF) is defined by worsening lung fibrosis on high-resolution computed tomography (HRCT), decline in lung function, and/or deterioration in symptoms. The INBUILD trial involved 663 patients with PPF who were randomized to receive nintedanib or placebo. The median exposure to trial medication was approximately 19 months. The INBUILD trial provided valuable learnings about the course of PPF and the efficacy and safety of nintedanib. The relative effect of nintedanib on reducing the rate of forced vital capacity decline was consistent across subgroups based on ILD diagnosis, HRCT pattern, and disease severity at baseline, and between patients who were and were not taking glucocorticoids or disease-modifying anti-rheumatic drugs and/or glucocorticoids at baseline. The adverse events most frequently associated with nintedanib were gastrointestinal, particularly diarrhea, but nintedanib was discontinued in only a minority of cases. The results of the INBUILD trial highlight the importance of prompt detection and treatment of PPF and the utility of nintedanib as a treatment option. Plain language summary: What did we find out from the INBUILD trial about progressive lung fibrosis? Lung fibrosis is a rare disease in which the lung tissue becomes scarred and hardened. This makes it more difficult for the lungs to inflate and for the lungs to exchange oxygen with the blood. In some patients, lung fibrosis gets worse over time. This is known as progressive lung fibrosis. In the INBUILD trial, researchers looked at the effects of a drug called nintedanib in patients with progressive lung fibrosis. In this trial, 663 patients were randomly allocated to receive either nintedanib or a placebo and then followed for approximately 19 months. The patients and the researchers did not know which patients were taking the active drug (nintedanib) and which patients were taking placebo. The results showed that the criteria used to find patients with progressive lung fibrosis to take part in the trial successfully identified patients whose disease would continue to worsen. These criteria were based on a decline in the volume (size) of the lungs, worsening symptoms such as shortness of breath, and worsening of changes seen on a scan of the chest. The trial results also showed that nintedanib slowed down loss of lung function and had a similar benefit in patients with different severities of disease at the start of the trial. The most common side-effects of nintedanib were gastrointestinal problems, particularly diarrhea, but most patients given nintedanib were able to cope with these side-effects without needing to stop treatment. Large trials like the INBUILD trial are important for helping us understand how diseases progress and in which patients particular drugs should be used. [ABSTRACT FROM AUTHOR]

Objective: Unusual clinical course Background: Melanoma differentiation associated gene-5 antibody (MDA-5 Ab) is one of the diagnostic autoantibodies that appears in idiopathic inflammatory myopathies (IIMs). Unlike when other autoantibodies are positive, when this antibody is positive, there is less characteristic muscle involvement. However, this MDA-5 Ab-positive myopathy presents extremely rapid progression of interstitial lung disease, resulting in a high mortality rate. Previous studies reported that the prognosis of this lung disease will be determined by the titer and suggest that low titers of MDA-5 antibody can indicate a good prognosis in associated interstitial lung disease. Case Report: Our case describes a 55-year-old woman who presented with acute respiratory symptoms and dyspnea. After hospitalization, symptoms and chest imaging worsened rapidly, and the radiology image of lung disease featured interstitial changes not seen in typical infections. We treated the patient with a high-flow oxygen nasal cannula, empirical antibiotics, and a systemic steroid. While treatment for a disease of unknown cause was continued, low titer of MDA-5 antibody was identified. Conclusions: This case suggests 2 points to consider about non-infectious interstitial changes with acute respiratory distress syndrome. First, when treating rapidly progressing interstitial pneumonia of an unknown cause, it is recommended to consider lung involvement of MDA-5 Ab dermatomyositis. Second, a low titer of MDA-5 Ab can be associated with better prognosis in this MDA-5 Ab dermatomyositis-related lung disease. [ABSTRACT FROM AUTHOR]

Interstitial lung diseases (ILD) are associated with various extrapulmonary complications, often leading to reduced exercise capacity. However, the relationship between exercise capacity and other clinical outcomes is not well established in the literature. To evaluate the association between exercise capacity and clinical outcomes in patients with ILD. This cross-sectional observational study included 42 patients aged 40 to 75 years who were diagnosed with ILD and were clinically stable. Patients were divided into two groups based on the median distance covered in the 6-minute walk test (6MWT): Group 1 (G1) included those who covered < 457 meters, while Group 2 (G2) comprised those who covered ≥ 457 meters. Participants underwent lung function tests, assessed their activities of daily living (ADL), measured global and peripheral muscle strength, and completed questionnaires evaluating quality of life, disease severity, sleep quality, sleepiness, and symptoms of anxiety and depression. The G1 covered 385 [327-415] meters on the 6MWT, while G2 covered 514 [490-590] meters. Statistical analysis showed significant differences between the groups in terms of daily steps, global muscle strength, upper limb strength, lower limb strength, and quality of life (p<0.05 for all). However, no differences were found between the groups concerning lung function, including FVC, FEV1, DLCO, symptoms of anxiety and depression, sleep quality, or sleepiness. Exercise capacity influences global and peripheral muscle strength, quality of life, and activities of daily living (ADL). However, there were no statistically significant differences in lung function, sleep quality, sleepiness, disease severity, or symptoms of anxiety and depression. [ABSTRACT FROM AUTHOR]

Idiopathic inflammatory myopathy (IIM) is a heterogeneous autoimmune disease of unknown etiology characterized by proximal limb muscle involvement and chronic inflammation. Multiple systems may be involved, with interstitial lung disease (ILD) being the most common manifestation of respiratory system involvement in IIM. This article summarizes the current methods of myositis animal models and myositis-associated ILD model construction methods, so as to provide reference for the subsequent construction and research of IIM-ILD models. [ABSTRACT FROM AUTHOR]

Clinical data of 16 patients diagnosed as CTD-ILD associated with lung cancer, who were admitted to our center, were retrospectively analyzed, including general conditions, clinical characteristics, auxiliary examinations, pathological classification of lung cancer, TNM type, treatment and clinical outcome. Results Among the 16 CTD-ILD patients with lung cancer, there were 12 males and 4 females. The mean age at diagnosis of CTD-ILD was (64.7±9.2) years, and the mean age at diagnosis of lung cancer was (66.6±8.7) years. Lung occupying space on imaging (62.5%) was the most common initial symptom in lung cancer patients, followed by cough and phlegm (12.5%) and chest pain (12.5%). Of patients with lung cancer, adenocarcinoma (8 cases, 50.0%) was the most common pathological type, followed by small cell lung cancer (4 cases, 25.0%). The diagnosis time of CTD-ILD was earlier than that of lung cancer in 8 cases (50.0%), with a median time of 36.0 (11.3, 57.0) months, followed by 7 cases (43.8%) of CTD-ILD diagnosed with lung cancer at the same time. The diagnosis time of lung cancer was earlier than that of CTD-ILD in 1 case (6.3%). The most common TNM stage for lung cancer was stage Ⅳ (9 cases, 56.25%). Sixteen patients were followed up from 1 to 64 months, with a median of 8.5 (1.5, 14.3) months. Eleven patients (68.8%) died, including 8 patients (72.7%) died of infection and 3 patients (27.3%) died of end-stage lung cancer. Conclusion For CTD-ILD patients, close follow-up and regular imaging monitoring are necessary to help early detection of lung cancer and improve prognosis. [ABSTRACT FROM AUTHOR]

Lymphocytic interstitial pneumonia (LIP) is a rare but largely benign interstitial lung disease, most frequently associated with HIV and autoimmune conditions. It is infrequently found to be an idiopathic condition. Diagnosis is complex and can require numerous invasive tests as evidenced in the case presented. The diagnosis is made from a combination of clinical, radiological, and histological features but the unusual radiological and clinical features meant diagnosis in our case required surgical biopsy. There is minimal evidence around best treatment although largely involves targeting the underlying cause. There is a small risk of transformation to lymphoma and fibrosis. Immunosuppression with steroids is the most common therapeutic strategy however in our case the radiographic changes spontaneously resolved. We present a case of an immunocompetent male presenting with significant radiological and histopathological findings of LIP, without significant symptomatology, that spontaneously resolved without intervention suggesting a monitoring approach may be a valid management strategy. [ABSTRACT FROM AUTHOR]

Background: Interstitial mycosis fungoides (IMF) is a rare subtype of mycosis fungoides (MF) characterized by atypical lymphocytes infiltrating the reticular dermis between collagen bundles with limited epidermotropism and variable granulomatous features. Methods: Retrospective single institution review of 31 cases of IMF including clinical characteristics, disease course and pathological features. Results: Our cohort was predominately male (19; 61%, M:F 1.6:1) with a mean age at diagnosis of 43 years (range 11–85), mean signs/symptoms duration of 7 years prior to diagnosis, and 6 years mean follow‐up duration. Clinically, patients often exhibited symmetric ill‐defined patches/plaques involving intertriginous regions with tan‐yellow hyperpigmentation and follicular‐based papules, wrinkling, and alopecia. Lymphadenopathy was noted in seven patients. Fifteen (52%) patients were in near or complete clinical remission at the latest follow‐up. T‐cell receptor gene rearrangement was positive in 23/24 (96%) cases. Histopathologically, atypical cells were small–medium, CD4+ (29; 94%) or rarely CD4+/CD8+ (1; 3%) lymphocytes infiltrating the reticular dermis with thickened collagen bundles (27; 87%), multinucleated giant cells (12; 39%), and often tracing along adnexa with subtle folliculotropism (12/20; 60%). Conclusions: Our study demonstrates IMF is an indolent subtype of MF with distinct features, including frequent granulomatous and subtle follicular involvement resulting in alopecia. [ABSTRACT FROM AUTHOR]

Atypical radiologic and clinical patterns may be observed within subgroups of lung adenocarcinoma. A 74-year-old man with progressive dyspnea and productive cough unresponsive to antibiotherapy showed bilateral interstitial changes in the lung parenchyma on computed tomography. We here report a patient followed up with a prediagnosis of interstitial lung disease but eventually diagnosed with lung adenocarcinoma following transthoracic lung biopsy. [ABSTRACT FROM AUTHOR]