Static analysis of gain control for a few-mode erbium-doped fiber amplifier employing pump power adjustment.

In mode-division multiplexing (MDM) optical transmission systems and MDM networks, the gain must be kept nearly constant even when the input signal power of the few-mode (FM), erbium-doped fiber amplifier (EDFA) changes. This paper investigates controllability of the gain in a 4-LP mode EDFA, whose EDF has signal modes of L P 01, L P 11, L P 21, and L P 02 or L P 01, L P 11, L P 21, and L P 31, by using analytical and full models. The results of calculation using the analytical model and a gain simulation using the full model show that the gain can be kept almost constant with an error less than 0.25 dB simply by adjusting the L P 01 pump power of the EDFA with signal modes of L P 01, L P 11, L P 21, and L P 31. This result suggests that it is possible to control the gain simply by adjusting the pump power in FM-EDFAs where all signal modes have a radial mode number of one.

1.8 µm band broadband hybrid light source employing a combination of a super luminescent diode and thulium-doped fiber amplifier.

We have proposed a broadband hybrid light source that combines a super luminescent diode (SLD) and thulium-doped fiber amplifier (TDFA) and operates in the 1.8 µm band. This light source can improve the characteristics of the output spectrum by amplifying the output light of the SLD with TDFA. In this study, we investigate the dependence of the output spectral characteristics of the hybrid broadband light source on the thulium-doped fiber (TDF) length used in the TDFA as well as the output spectra of three newly developed SLDs of 1660, 1690, and 1730 nm bands. In the evaluation of the output bandwidth, there are various definitions of output bandwidth, but we adopted the bandwidth with power density of over -40dBm/0.1nm. This is because it is possible to evaluate in this band with a dynamic range of "30 dB/0.1 nm" by using a general optical spectrum analyzer. The hybrid light source achieves the bandwidth of 332 nm, from 1579 to 1911 nm, and a high total output power of over 15 dBm. The maximum ripple was less than ∼0.1dB, which is similar to the maximum value of that of the SLD, without any deterioration in the ripple characteristics owing to the hybrid configuration of the SLD and TDFA.

Efficacy of early antifibrotic treatment for idiopathic pulmonary fibrosis.

BACKGROUND: Although antifibrotic drugs, including nintedanib and pirfenidone, slow the progression of idiopathic pulmonary fibrosis (IPF), there is little data about the timing of start of antifibrotic treatment in real-world clinical practice. The present study aimed to clarify the efficacy of nintedanib and pirfenidone in patients with early-stage IPF. METHODS: We compared survival and disease progression between patients with IPF with Japanese Respiratory Society (JRS) disease severity system stage I with and without oxygen desaturation on the 6-min walk test (6MWT) and increased the gender-age-physiology (GAP) staging. We examined the efficacy of antifibrotic drugs in patients with early-stage IPF. RESULTS: The severity of stage I IPF (n = 179) according to the JRS criteria consisted of the following GAP staging criteria: stage I, 111 cases; stage II, 58 cases; stage III, 10 cases. The duration from the initial visit to disease progression and survival time was significantly shorter in JRS stage I patients with oxygen desaturation on the 6MWT or with increased GAP staging (unfavorable group) compared with patients without those factors. In the unfavorable group, the relative decline in percentage predicted forced vital capacity (%FVC) over 6 months was significantly lower in patients undergoing antifibrotic treatment compared with non-treated patients. CONCLUSION: Antifibrotic drugs have a beneficial effect on the decline in %FVC in Japanese patients with early-stage IPF who have oxygen desaturation on the 6MWT or increased GAP staging.

Association of Immune-Related Adverse Events with Clinical Benefit in Patients with Advanced Non-Small-Cell Lung Cancer Treated with Nivolumab.

BACKGROUND: Immune-related adverse events (irAEs) are frequently observed with nivolumab monotherapy. This study aimed to evaluate whether the development of irAEs correlates with treatment response in advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: We conducted a retrospective study of patients who received nivolumab monotherapy at Sendai Kousei Hospital (n = 70). The patients were categorized into two groups based on the incidence of irAEs: those with irAEs (irAE group) or those without (non-irAE group). Treatment efficacy was evaluated in each group. The patients were further categorized into responders and nonresponders, and predictive factors of treatment response were determined. RESULTS: The objective response rate was 57% in the irAE group versus 12% in the non-irAE group. Median progression-free survival was 12.0 months in the irAE versus 3.6 months in the non-irAE group. The incidence of both irAEs and pre-existing antithyroid antibody was significantly higher in responders than in nonresponders. Multivariate analysis identified incidence of irAEs and pre-existing antithyroid antibody as an independent predictor of treatment response. CONCLUSION: Objective response rate and progression-free survival were significantly better in the irAE than in the non-irAE group in patients with advanced NSCLC treated with nivolumab monotherapy. The development of irAEs was associated with clinical efficacy, and the presence of pre-existing antithyroid antibody might be correlated with treatment response to nivolumab monotherapy. IMPLICATIONS FOR PRACTICE: Immune-related adverse events (irAEs) are frequently observed with nivolumab monotherapy. This study evaluted whether the development of irAEs correlates with treatment response in advanced non-small-cell lung cancer. Results showed that the objective response rate and progression-free survival were significantly better in the patients who developed irAEs than in the patients who did not develop irAEs, and the incidence of irAEs and positivity for antithyroid antibody at pretreatment were independent predictors of treatment response of nivolumab monotherapy. Therefore, the development of irAEs predicts clinical benefit and suggests that cautious management of irAEs can lead to achieving maximum clinical benefit from nivolumab monotherapy.

Hybrid cladding-pumped multicore EDFA/Raman amplification for space division multiplexing transmission systems.

We propose and demonstrate a hybrid cladding-pumped multicore erbium-doped fiber amplifier (EDFA) and distributed Raman amplification for space division multiplexing transmission systems. The cladding-pumped multicore EDFA is used to efficiently amplify signals in multiple cores simultaneously, while Raman pumping is used to control loss in each core individually. We construct an in-line amplified 7-core transmission line, and show that distributed Raman amplification can compensate loss variation between cores. Furthermore, we transmit 46 WDM PDM-16QAM signals over a long distance of greater than 1000 km and demonstrate good transmission performance.

Applicability of a model with average inversion level to a cladding-pumped multicore erbium-doped fiber amplifier.

This paper investigates the applicability of a model of a cladding-pumped multicore erbium-doped fiber amplifier (CP-MC-EDFA) that employs the average inversion level of an erbium ion. The model is modified to include the effects of multiple cores for modifications of the background loss coefficient of the pump light. The model is validated experimentally by measurements of the pump power, gain transient, and intercore cross-gain modulation of a cladding-pumped 12-core EDFA in which the pump light is uniformly distributed in the inner cladding. The calculated and measured pump power, gain transient response, and gain change caused by the intercore cross-gain modulation agree well, suggesting the modified model is useful for characterizing a CP-MC-EDFA.

2-LP mode few-mode fiber amplifier employing ring-core erbium-doped fiber.

A fiber amplifier supporting 2 LP modes that employs a ring-core erbium-doped fiber (RC-EDF) is investigated to reduce differential modal gain (DMG). The inner and outer radii of the ring-core of the RC-EDF are clarified for 2-LP mode operation of the amplifier, and are optimized to reduce the DMG. It is shown that using the overlap integral between the erbium-doped core area and the signal power mode distribution is a good way to optimize the inner and outer radii of the ring-core of the RC-EDF and thus minimize the DMG. A fabricated RC-EDF and a constructed 2-LP mode EDFA are described and a small DMG of around 1 dB is realized for LP01, LP11 and LP21 pumping.

Method for estimating gain coefficient spectrum of erbium-doped fiber based on net gain-loss measurement employing 4I(13/2) level pumping.

The method for estimating the gain coefficient spectrum of an erbium-doped fiber (EDF) is proposed and demonstrated experimentally. The method employs a net gain-loss measurement that uses the 4I(13/2) level pumping of the EDF and the McCumber relation. A formula used to obtain the quotient of the gain and loss coefficient from the net gain-loss measurement is derived to determine the parameter in the McCumber relation. It is confirmed that the gain coefficient spectrum of an EDF estimated with the method coincides with the value estimated using a conventional net gain-loss measurement that employs the 4I(11/2) level pumping. The method is successfully applied to an erbium/ytterbium-doped fiber, for which it is impossible to perform a conventional net gain-loss measurement with pumping at the 4I(11/2) level of erbium ions because of the absorption transition of ytterbium ions from 2F(7/2) to 2F(5/2) levels.

Tolerability and efficacy of switching anti-fibrotic treatment from nintedanib to pirfenidone for idiopathic pulmonary fibrosis.

BACKGROUND: In real-world studies, the rate of discontinuation of nintedanib (NT) varies from 4% to 53%. Switching anti-fibrotic treatment in patients with idiopathic pulmonary fibrosis (IPF) has not been adequately investigated, and data on the tolerability and efficacy of changes in anti-fibrotic treatment is limited in clinical practice. OBJECTIVE: To identify factors associated with poor continuation of NT, efficacy and predictors of deterioration after switching from NT to pirfenidone (PFD) in patients with IPF. SUBJECTS AND METHODS: One hundred and seventy patients with IPF in whom NT was introduced between April 2017 and March 2022 were included to investigate NT continuation status and the effect of switching to PFD. RESULTS: A total of 123 patients (72.4%) continued NT for 1 year and had a significantly higher %forced vital capacity (FVC) at NT introduction than those who discontinued within 1 year (80.9% ± 16.3% vs. 71.9% ± 22.1%, P = 0.004). The determinant of poor NT continuation was the high GAP stage. On the other hand, 28 of 36 patients who discontinued NT because of disease progression switched to PFD. Consequently, FVC decline was suppressed before and after the change. The predictor of deterioration after the switch was a lower body mass index. CONCLUSIONS: In patients with IPF, early NT introduction increased continuation rates, and switching to PFD was effective when patients deteriorated despite initial NT treatment.

409-Tb/s + 409-Tb/s crosstalk suppressed bidirectional MCF transmission over 450 km using propagation-direction interleaving.

We demonstrate bidirectional transmission over 450 km of newly-developed dual-ring structured 12-core fiber with large effective area and low crosstalk. Inter-core crosstalk is suppressed by employing propagation-direction interleaving, and 409-Tb/s capacities are achieved for both directions.

Pleuroparenchymal fibroelastosis in mycobacterium avium complex lung disease.

We report a rare case of pleuroparenchymal fibroelastosis (PPFE) with interstitial lung disease progressed after an onset of mycobacterium avium complex (MAC) lung disease. Clinicians should pay attention to the management for patients with PPFE in MAC lung disease.

Successful baricitinib treatment of refractory anti-synthetase syndrome associated with interstitial lung disease.

A 47-year-old Japanese man was admitted with dyspnoea on exertion (DOE), skin rash and myalgia. Clinical findings of Gottron's sign and mechanic's hands were observed, with increased serum levels of Krebs von den Lungen-6, surfactant protein-D, creatine kinase, and anti-EJ on laboratory tests. In both lungs, chest computed tomography revealed diffuse reticular opacities and lower lobe predominance. The patient was diagnosed with anti-synthetase syndrome (ASS) and associated interstitial lung disease. Despite repeated administration of high-dose intravenous corticosteroids, cyclophosphamide and immunoglobulin, his skin rash, myalgia, and DOE followed a relapsing and remitting course. He was then given rituximab therapy. This was initially successful, but disease activity increased approximately 12 months after starting rituximab therapy. Finally, in addition to prednisolone and cyclosporine A, we administered baricitinib. There has been no relapse of the disease in the 12 months since he began baricitinib treatment.

1000-km 7-core fiber transmission of 10 x 96-Gb/s PDM-16QAM using Raman amplification with 6.5 W per fiber.

We demonstrate 7-core fiber transmission of 10 x 96-Gb/s PDM-16QAM signals over 1000-km using distributed Raman amplification (DRA). DRA gain of 9-12 dB and equivalent noise figure of less than 1 dB are achieved in all cores. We also prove the feasibility of high power multi-core fiber transmission with per fiber power of 6.5 W.

Coronavirus disease 2019 vaccination-induced acute exacerbation in idiopathic pulmonary fibrosis.

We report a rare case of acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) after coronavirus disease 2019 (COVID-19) vaccination. Clinicians should be aware of this COVID-19 vaccination-induced AE in IPF.

Multiple endotracheal metastases of combined small cell lung carcinoma.

We report a very rare case of combined small cell lung carcinoma (C-SCLC) which presented as persistent cough and was due to endotracheal metastases. Clinicians should be aware of this unusual site of metastases from a C-SCLC.

Immunoglobulin G4-positive interstitial pneumonia associated with pleuroparenchymal fibroelastosis.

A 79-year-old former smoking Japanese man was admitted to our hospital with a 2-year history of dry cough and dyspnoea on exertion. High-resolution computed tomography of the chest revealed reticulation and perilobular opacity with bronchial wall thickening and ground-glass opacities (GGOs) in both lungs, in addition to subpleural dense consolidation (pleuroparenchymal fibroelastosis-like lesion; PPFE-like lesion) predominantly in the bilateral upper lobes. Serum immunoglobulin G4 (IgG4) was elevated (348 mg/dl). Lung biopsy specimens obtained by video-assisted surgery revealed a mixture of usual interstitial pneumonia (IP) and non-specific IP pattern admixed with PPFE. In addition, immunohistochemical staining of IgG4 showed numerous IgG4-positive plasma cells. Consequently, he was diagnosed with IgG4-positive IP associated with PPFE. We initiated a combination therapy with prednisolone and cyclosporine as a calcineurin inhibitor. During prednisolone tapering, his clinical conditions and GGOs improved gradually over 12 months. However, reticular opacities and PPFE-like lesions remained unchanged, and pulmonary function test findings slightly deteriorated.

Efficacy and safety of oral semaglutide in patients with non-alcoholic fatty liver disease complicated by type 2 diabetes mellitus: A pilot study.

Background and Aim: This study aimed to clarify the efficacy and safety of oral semaglutide treatment in patients with non-alcoholic fatty liver disease (NAFLD) complicated by type 2 diabetes mellitus (T2DM). Methods: This was a single-arm, open-label pilot study. Sixteen patients with NAFLD who received oral semaglutide for T2DM were included in the analysis. Oral semaglutide was initiated at a dose of 3 mg once daily, and the dose was sequentially increased to 7 mg at 4 weeks and 14 mg at 8 weeks (maintenance dose) until the end of the 24-week trial. Results: Body weight and levels of liver-related biochemistry, plasma glucose, and hemoglobin A1c decreased significantly from baseline to 12 weeks. These significant decreases were maintained until the end of the trial. Additionally, levels of the homeostasis model assessment-insulin resistance and triglyceride significantly decreased at 24 weeks. Controlled attenuation parameter (CAP) values significantly decreased from baseline to 24 weeks. Changes in body weight were correlated with those in levels of alanine aminotransferase (r = 0.52) and CAP (r = 0.72). As for liver fibrosis markers, significant decreases from baseline to 24 weeks in levels of the fibrosis-4 index, ferritin, and type IV collagen 7 s were found; however, the liver stiffness measurement did not significantly decrease. Most adverse events were grade 1-2 transient gastrointestinal disorders. Conclusions: Oral semaglutide treatment in patients with NAFLD complicated by T2DM improved impaired liver function, hypertriglyceridemia, insulin resistance, and hepatic steatosis, as well as improving diabetic status and reducing body weight.

Eosinophilic bronchiolitis successfully treated with benralizumab.

A 53-year-old non-smoking Japanese woman was admitted to our hospital with a 20-year history of wet cough and dyspnoea on exertion. Bronchial asthma (BA) had been diagnosed 20 years earlier. Although she has been treated with high-dose inhaled corticosteroid, she had experienced frequent exacerbation of BA, and short-term oral corticosteroid bursts were occasionally administered. High-resolution CT of the chest revealed diffuse centrilobular nodules with bronchial wall thickening and patchy ground-glass opacities in both lungs. Lung biopsy specimens showed widespread cellular bronchiolitis with follicle formations in the membranous and respiratory bronchioles, accompanied by marked infiltration of plasma cells and eosinophils. In addition, immunohistochemical immunoglobulin G4 (IgG4) staining revealed many IgG4-positive plasma cells, and the ratio of IgG4-positive cells to IgG-positive cells exceeded 40%. The final diagnosis was eosinophilic bronchiolitis with marked IgG4-positive plasma cell infiltration in association with BA. With benralizumab therapy, her clinical condition dramatically improved.

Post-coronavirus disease 2019 organizing pneumonia confirmed pathologically by video-assisted thoracoscopic surgery.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, has become a global pandemic. Many survivors of serious COVID-19 pneumonia have long-term residual pulmonary disease. However, there is little documentation of the histopathological characteristics of lung sequelae post-COVID-19 and effective treatments. We present two Japanese cases of lung sequelae post-COVID-19. The patients were histopathologically diagnosed with organizing pneumonia (OP) or OP with fibrosis and no diffuse alveolar damage on video-assisted thoracoscopic surgery. Case 1, who had been diagnosed with OP, was successfully treated with corticosteroid and other immunosuppressive agents over a 6-month period. Although case 2, who had been diagnosed with OP with fibrosis, had a partial and unsatisfactory response to immunosuppressive agents, the patient responded to antifibrotic treatment including nintedanib.

Acute exacerbation in chronic bird fancier's lung with pleuroparenchymal fibroelastosis.

A 71-year-old non-smoker woman was admitted to our hospital complaining of a six-month history of dry cough. She had kept java sparrow for nine years and has been raising budgerigars for the previous eight months. High-resolution computed tomography (HRCT) images of the chest revealed reticulonodular lesions predominantly in the bilateral upper lobes. Surgical lung biopsy specimens showed non-caseous epithelioid cell granulomas in the alveolar spaces, including irregular and centrilobular fibrosis with pleuroparenchymal fibroelastosis. When she started using a duck feather duvet at home, she developed dyspnoea and chest HRCT abnormalities progressively deteriorated. The results of precipitation of antibodies against duck feather, java sparrow, and budgerigars dropping extracts were positive in sera. Consequently, the patient was diagnosed as having chronic bird fancier's lung with acute exacerbation caused by the use of a feather duvet. After combination treatments with corticosteroid and cyclosporine, her respiratory symptoms and reticulonodular shadow immediately improved.