Usefulness of Transbronchial Lung Cryobiopsy When Starting Antifibrotic Treatment and Predicting Progressive Fibrosing Interstitial Lung Disease: Descriptive Research.

BACKGROUND: Although transbronchial lung cryobiopsy (TBLC) is widely used in diagnostic algorithms for various interstitial lung diseases (ILDs), its real-world utility in the therapeutic decision-making strategy for ILD patients remains unclear, in particular, when judging the time to start antifibrotic agents. METHODS: We analyzed medical records of 40 consecutive patients with idiopathic or fibrotic hypersensitivity pneumonitis who underwent TBLC. A TBLC-based usual interstitial pneumonia (UIP) score was used to assess three morphologic descriptors: patchy fibrosis, fibroblastic foci, and honeycombing. RESULTS: In our 40 patients with ILD, the most frequent radiological feature was indeterminate for UIP (45.0%). Final diagnosis included idiopathic pulmonary fibrosis (22.5%), fibrotic nonspecific interstitial pneumonia (5.0%), fibrotic hypersensitivity pneumonitis (35.0%), and unclassifiable ILD (37.5%). Linear mixed-effects analysis showed that declines in the slopes of %FVC and %DLCO in patients with TBLC-based UIP "Score ≥ 2" were significantly steeper than those of patients with "Score ≤ 1." During follow-up of patients with Score ≥ 2 (n = 24), more than half of them (n = 17) received an antifibrotic agent, with most patients (n = 13) receiving early administration of the antifibrotic agent within 6 months after the TBLC procedure. CONCLUSIONS: TBLC-based UIP Score ≥ 2 indicated the increased possibility of a progressive fibrosis course that may prove helpful in predicting progressive pulmonary fibrosis/progressive fibrosing ILD even if disease is temporarily stabilized due to anti-inflammatory agents. Patients may benefit from early introduction of antifibrotic agents by treating clinicians.

Inhalable FN-binding liposomes or liposome-exosome hybrid bionic vesicles encapsulated microparticles for enhanced pulmonary fibrosis therapy.

Pulmonary fibrosis (PF) is a chronic, progressive and irreversible interstitial lung disease that seriously threatens human life and health. Our previous study demonstrated the unique superiority of traditional Chinese medicine cryptotanshinone (CTS) combined with sustained pulmonary drug delivery for treating PF. In this study, we aimed to enhance the selectivity, targeting efficiency and sustained-release capability based on this delivery system. To this end, we developed and evaluated CTS-loaded modified liposomes-chitosan (CS) microspheres SM(CT-lipo) and liposome-exosome hybrid bionic vesicles-CS microspheres SM(LE). The prepared nano-in-micro particles system integrates the advantages of the carriers and complements each other. SM(CT-lipo) and SM(LE) achieved lung myofibroblast-specific targeting through CREKA peptide binding specifically to fibronectin (FN) and the homing effect of exosomes on parent cells, respectively, facilitating efficient delivery of anti-fibrosis drugs to lung lesions. Furthermore, compared with daily administration of conventional microspheres SM(NC) and positive control drug pirfenidone (PFD), inhaled administration of SM(CT-lipo) and SM(LE) every two days still attained similar efficacy, exhibiting excellent sustained drug release ability. In summary, our findings suggest that the developed SM(CT-lipo) and SM(LE) delivery strategies could achieve more accurate, efficient and safe therapy, providing novel insights into the treatment of chronic PF.

Efficacy and safety of Dynavisc® gel in prevention of scar adhesions recurrence after flexor tendons tenolysis in zone 2. Multicenter retrospective cohort study.

AIM: Dynavisc® is a novel surgical product made of carboxymethylcellulose (CMC) and Polyethylene Oxide (PEO) designed to reduce post-surgical adhesions in tendons surgery. A multicenter retrospective cohort study was performed to investigate the clinical safety and efficacy of the Dynavisc® gel in reducing post-surgical adhesions after flexor tenolysis in zone 2. MATERIAL OF STUDY: Thirty-one patients suffering from stiff finger after flexor tendon repairs in zone 2 treated with standard release with (18 Dynavisc®-treated group) or without (13 controls) anti-adhesion gel application into the flexor tendon sheath and around the site of the tenolysis, were collected in five different hand surgery units. Safety profile and functional outcomes (based on TAM test and the The Quick-DASH questionnaire) were examined from patients' charts and analyzed. RESULTS: The application of Dynavisc® posed no safety concerns and it was not related to any additional complication. The Dynavisc®-treated group showed greater progressive improvement of TAM value in all visits with superior TAM value at T(90) and T(180) compared to the control group. DISCUSSION: Tendon adhesions are the main cause of flexor tendon surgery failure. Multiple strategies (i.e. robust tendon repair, early rehabilitation and lubricant or barrier agents) have been proposed to minimize their formation. Among different products described in the literature Dynavisc® showed a significant role in limiting adhesions formation in a recent experimental study. CONCLUSIONS: This clinical study confirm the safety of Dynavisc® gel application in hand surgery demonstrating its potential long-term benefits after flexor tendon tenolysis. KEY WORDS: Flexor Tendon Repair, Tendon Adhesions, Tenolysis.

Potential antifibrotic effect of blueberry and grape polyphenol extracts in acute and subacute bleomycin-induced lung tissue injury models in mice / Potencial efecto antifibrótico de los extractos de polifenoles de arándano y uva en modelos de lesión tisular pulmonar aguda y subaguda inducida por bleomicina en ratones

SUMMARY: An experimental morphological and morphometric study of the antifibrotic function of blueberry and grape extracts was carried out on a model of lung injury in mice induced by intraperitoneal administration of bleomycin. During intraperitoneal administration of bleomycin to mice, acute and subacute damage to the pulmonary system was noted. Both patterns had the same prevalence and severity. The administration of polyphenolic extracts of blueberry and grape to mice showed a significant reduction in the severity of the acute and subacute pattern of lung injury. Blueberry and grape extracts reduce the acute phase of damage to the microvasculature, enhance phagocytic function, have an anti-inflammatory effect, reducing the degree of lymphohistiocytic infiltration and locoregional foci of residual inflammatory effects.

Se realizó un estudio experimental morfológico y morfométrico de la función antifibrótica de extractos de arándano y uva en un modelo de lesión pulmonar en ratones inducida por la administración intraperitoneal de bleomicina. Durante la administración intraperitoneal de bleomicina a ratones, se observaron daños agudos y subagudos en el sistema pulmonar. Ambos patrones tuvieron la misma prevalencia y severidad. La administración de extractos polifenólicos de arándano y uva a ratones mostró una reducción significativa en la severidad del patrón agudo y subagudo de lesión pulmonar. Los extractos de arándano y uva reducen la fase aguda del daño a la microvasculatura, mejoran la función fagocítica, tienen un efecto antiinflamatorio, reducen el grado de infiltración linfohistiocítica y los focos locorregionales de efectos inflamatorios residuales.

Is it possible to repigment iatrogenic and traumatic hypochromic lesions? A case series using the MMP® drug delivery technique with 5-fluorouracil and bleomycin.

OBJECTIVES: We present the results of 11 patients with hypochromic lesions treated with antifibrotic agents delivered through the MMP® technique. METHODS: Eleven patients with hypochromic lesions because of external injuries were treated at a single clinic with 5-fluorouracil (5-FU) and/or bleomycin using the MMP® drug delivery technique. Treatment sessions were repeated at 30-day intervals until patient satisfaction. The primary outcome was repigmentation of the lesions, assessed independently by two dermatologists and by the patient. RESULTS: The MMP® technique injected 0.048 mg/cm2 of 5-FU or 0.0028 U/cm2 of bleomycin. The accumulated 5-FU and bleomycin density per patient ranged from 0.02 to 0.77 mg and 0.0022 to 0.2800 U/ml, respectively. Patients were treated with 1 to 6 MMP® sessions with 5-FU (3 patients), bleomycin (6 patients), or both drugs (2 patients). After the last session, all patients had a significant improvement (>75%) of the lesions compared to baseline. There were no procedure-related short- or long-term adverse effects in any of the participants up to their last follow-up visit. CONCLUSIONS: The injection of antifibrotic agents using the MMP® technique was effective and safe in the treatment of hypochromic lesions. This can be a new therapeutic option for these lesions.

Feasibility and safety of treatment switch from Pirfenidone to Nintedanib in patients with idiopathic pulmonary fibrosis: a real-world observational study.

OBJECTIVE: Idiopathic Pulmonary Fibrosis is a disease characterized by a devastating fibrosing process. Two anti-fibrotic agents, pirfenidone and nintedanib, have been found to alter the disease progression. In this study, we sought to determine whether switching treatment to nintedanib is feasible and safe in patients that had to discontinue treatment with pirfenidone due to side effects. PATIENTS AND METHODS: We analyzed patients that had to discontinue pirfenidone due to side effects. Patients were prospectively enrolled for treatment with nintedanib between March 2015 and June 2019. Side effects and Pulmonary Function Tests were recorded. RESULTS: 12 patients received nintedanib after discontinuing treatment with pirfenidone. Side-effects that led to discontinuation were diarrhea (33.3%), nausea (16.6%), photosensitivity (33.3%) and difficulty adhering to pirfenidone's dosage scheme (16.6%). After the initiation of nintedanib, diarrhea was the most common side effect (66.6%). Four patients of these patients could not tolerate the full dose of 300 mg daily and had to reduce it to 200 mg daily. No patient has had experienced liver damage. During the last twelve months of treatment with pirfenidone, mean ΔFCV was +2.47 ± 3.69%, mean ΔDLco was -0.36 ± 2.64% and mean difference of the distance walked during the 6MWT was 5 ± 56.48 meters. During the first year of treatment with nintedanib, mean ΔFCV was -1.32 ± 1.12% (p=0.68), mean ΔDLco was -1.59 ± 3.45% (p=0.54) and mean difference of the distance walked during the 6MWT was 14.17 ± 59 meters (p=0.078). 50% of patients had stable disease under pirfenidone (6-month FVC decline < 5% and/or 6-month DLco decline < 10%) vs. 50% under nintedanib, 33.3% had marginal 6-month decline (5% ≤ 6-month FVC ≤ 10% and/or (≤ 10% 6- month DLco decline ≤15%) under pirfenidone vs. 33.3% under nintedanib and 16.6% had disease progression (6-month FVC decline > 10% and/or 6-month DLco decline > 15%) under pirfenidone vs. 16.6% under nintedanib. CONCLUSIONS: These results suggest that nintedanib is a safe option for the treatment of patients that had to discontinue pirfenidone due to adverse reactions. Further studies with greater patient numbers are needed for accurate results concerning efficacy.

Myeloperoxidase and associated lung disease: Review of the latest developments.

Myeloperoxidase (MPO) anti-neutrophil cytoplasmic antibodies (ANCA) are often detected in association with a variety of lung pathologies, the most common being interstitial lung disease (ILD). A growing cohort of patients are being diagnosed with MPO-ANCA in the context of ILD without ANCA-associated vasculitis. Clinically and radiologically, there is little to differentiate this cohort from MPO-ANCA-negative ILD patients; however, the pathophysiology is likely different and different treatments are likely required. We present here a brief summary of the proposed pathophysiology of MPO-ANCA-positive ILD, and a more detailed review of the latest evidence on management, including monitoring for development of ANCA-associated vasculitis, immunosuppression, anti-fibrotics, and novel agents that have yet to be trialled in human experiments.

Molecular and Clinical Elucidation of the Mechanism of Action of Steroids in Idiopathic Carpal Tunnel Syndrome.

BACKGROUND: Carpal tunnel steroid injection is a nonoperative intervention for the treatment for idiopathic carpal tunnel syndrome (CTS). The antifibrotic, anti-inflammatory, and antiedematous properties of steroids account for their therapeutic effects in the context of CTS; however, their relative contribution has not been clarified. METHODS: Fibroblasts from subsynovial connective tissues (SSCT) were intraoperatively collected from patients with idiopathic CTS and were incubated with or without the steroid triamcinolone acetonide (TA) for 1, 3, and 7 days; the expression of fibrosis-related genes and inflammatory cytokines was evaluated using quantitative reverse transcription-polymerase chain reaction. A clinical prospective study was conducted with patients who received carpal tunnel TA injections. We performed clinical and electrophysiological evaluations before and 1, 3, and 5 months after TA injection; and we compared the median nerve, flexor tendon, and SSCT areas and the median nerve flattening ratio before and 1 month after TA injection using 3-T magnetic resonance imaging (MRI). RESULTS: TA induced downregulation of the fibrosis-related genes Col1A1 (collagen type I alpha 1 chain), Col1A2, and Col3A1 but not the inflammation-related genes. The nerve flattening ratio did not change after TA injection according to the MRI-based observation of the median nerve, flexor tendon, and SSCT areas. CONCLUSIONS: The therapeutic effects of injected TA are apparently mediated by its antifibrotic rather than its anti-inflammatory and antiedematous properties. TA probably alters the properties but not the morphology of SSCT. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

The Influence of Indentation Deformity on Outcomes With Intralesional Collagenase Clostridium Histolyticum Monotherapy for Peyronie's Disease.

OBJECTIVE: To identify patient-specific factors associated with patient-reported improvements in functional outcomes after intralesional Collagenase Clostridium histolyticum (CCH) for Peyronie's Disease (PD). METHODS: We retrospectively explored our prospectively maintained CCH registry. We sought to identify patient-specific factors that prevented the need for surgical straightening and/or improved ability to engage in penetrative intercourse. RESULTS: Eighty-six patients underwent CCH monotherapy and had objective follow-up data available. Mean PD symptom duration was 25 months (SD 44) and baseline curvature was 65o (SD 24). Prominent indentation/hourglass deformities (defined as girth discrepancy >10%) were present in 40 patients (47%). Mean objective curve improvement was 19o (SD 20), and 60% achieved improvement ≥15o. Greater baseline curvature was associated with greater absolute improvements in curvature, although there was no association between baseline curvature and relative (%) improvement. Three of 40 patients (8%) with indentation achieved girth improvement. Patients with baseline indentation/hourglass were less likely to report that CCH prevented the need for surgery (35% vs 64%, P = .018). Patients with curve improvement <15o were also less likely to report that CCH prevented the need for surgery (25% vs 63%, P = .0086) or improved penetration (54% vs 89%, P = .018). There were no differences in outcomes based on age, BMI, symptom duration, and presence of biplanar curvature. CONCLUSION: Baseline indentation/hourglass deformity and curve improvement <15o are associated with less favorable functional improvements such as preventing the need for surgery and improving penetration.