Durvalumab, with or without tremelimumab, plus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer: 3-year overall survival update from CASPIAN.

BACKGROUND: In the phase III CASPIAN study, first-line durvalumab in combination with etoposide plus either cisplatin or carboplatin (EP) significantly improved overall survival (OS) versus EP alone in extensive-stage small-cell lung cancer (ES-SCLC). Durvalumab plus tremelimumab plus EP numerically improved OS versus EP, but did not reach statistical significance. Here we report updated OS in censored patients after median follow-up of >3 years. PATIENTS AND METHODS: 805 patients with treatment-naïve ES-SCLC were randomized 1 : 1 : 1 to durvalumab plus EP, durvalumab plus tremelimumab plus EP, or EP. The two primary endpoints were OS for durvalumab plus EP versus EP and for durvalumab plus tremelimumab plus EP versus EP. RESULTS: As of 22 March 2021 (median follow-up 39.4 months, 86% maturity), durvalumab plus EP continued to demonstrate improved OS versus EP: hazard ratio (HR) 0.71 [95% confidence interval (CI) 0.60-0.86; nominal P = 0.0003]; median OS was 12.9 versus 10.5 months, and 36-month OS rate was 17.6% versus 5.8%. Durvalumab plus tremelimumab plus EP continued to numerically improve OS versus EP: HR 0.81 (95% CI: 0.67-0.97; nominal P = 0.0200); median OS was 10.4 months, and 36-month OS rate was 15.3%. Twenty-seven and nineteen patients in the durvalumab plus EP and durvalumab plus tremelimumab plus EP arms, respectively, remained on durvalumab treatment at data cut-off. CONCLUSIONS: Three times more patients were estimated to be alive at 3 years when treated with durvalumab plus EP versus EP, with the majority still receiving durvalumab at data cut-off, further establishing durvalumab plus EP as first-line standard of care for ES-SCLC.

A randomized phase III trial comparing adjuvant single-agent S1, S-1 with oxaliplatin, and postoperative chemoradiation with S-1 and oxaliplatin in patients with node-positive gastric cancer after D2 resection: the ARTIST 2 trial☆.

BACKGROUND: Adjuvant chemotherapy and chemoradiotherapy are some of the standards of care for gastric cancer (GC). The Adjuvant chemoRadioTherapy In Stomach Tumors (ARTIST) 2 trial compares two adjuvant chemotherapy regimens and chemoradiotherapy in patients with D2-resected, stage II or III, node-positive GC. PATIENTS AND METHODS: The ARTIST 2 compared, in a 1:1:1 ratio, three adjuvant regimens: oral S-1 (40-60 mg twice daily 4 weeks on/2 weeks off) for 1 year, S-1 (2 weeks on/1 week off) plus oxaliplatin 130 mg/m2 every 3 weeks (SOX) for 6 months, and SOX plus chemoradiotherapy 45 Gy (SOXRT). Randomization was stratified according to surgery type (total or subtotal gastrectomy), pathologic stage (II or III), and Lauren histologic classification (diffuse or intestinal/mixed). The primary endpoint was disease-free survival (DFS) at 3 years; a reduction of 33% in the hazard ratio (HR) for DFS with SOX or SOXRT, when compared with S-1, was considered clinically meaningful. The trial is registered at clinicaltrials.gov (NCT0176146). RESULTS: A total of 546 patients were recruited between February 2013 and January 2018 with 182, 181, and 183 patients in the S-1, SOX, and SOXRT arms, respectively. Median follow-up period was 47 months, with 178 DFS events observed. Estimated 3-year DFS rates were 64.8%, 74.3%, and 72.8% in the S-1, SOX, and SOXRT arms, respectively. HR for DFS in the control arm (S-1) was shorter than that in the SOX and SOXRT arms: S-1 versus SOX, 0.692 (P = 0.042) and S-1 versus SOXRT, 0.724 (P = 0.074). No difference in DFS was found between SOX and SOXRT (HR 0.971; P = 0.879). Adverse events were as anticipated in each arm, and were generally well-tolerated and manageable. CONCLUSIONS: In patients with curatively D2-resected, stage II/III, node-positive GC, adjuvant SOX or SOXRT was effective in prolonging DFS, when compared with S-1 monotherapy. The addition of radiotherapy to SOX did not significantly reduce the rate of recurrence after D2 gastrectomy.

Detection of combined procalcitonin and c-reactive protein applied in the diagnosis of bacterial infections.

In recent years, procalcitonin and C-reactive protein have been used as important indexes in the detection of inflammation. In order to analyze the combined detection of procalcitonin and C-reactive protein in infected patients, 57 subjects in the Clinical Laboratory of Zhengzhou Maternal and Child Health Hospital with a bacterial infection were selected as the observation group. Correspondingly, 57 non-infected subjects were selected for the control group. The procalcitonin and C-reactive protein levels in the included cases were analyzed and compared by extracting peripheral blood. The results showed that the two indexes of C-reactive protein (46.13±8.24 mg/L) and procalcitonin (6.61±3.45 ug/L) of the observation group were significantly higher than those of the control group (P less than 0.05). The positive rates of C-reactive protein (71.93%) and procalcitonin (91.23%) of the observation group were significantly higher than those of the control group (P less than0.05). Within the observation group, the C-reactive protein and procalcitonin levels in the infected patients after 2 and 3 days of treatment, decreased significantly (P less than 0.05). This study indicates that the combined detection of procalcitonin and C-reactive protein in patients with bacterial infections is effective and can be used in clinical settings.

Performance evaluations of hybrid modulation with different optical labels over PDQ in high bit-rate OLS network systems.

Two orthogonal modulation optical label switching(OLS) schemes, which are based on payload of polarization multiplexing-differential quadrature phase shift keying(POLMUX-DQPSK or PDQ) modulated with identifications of duobinary (DB) label and pulse position modulation(PPM) label, are researched in high bit-rate OLS network. The BER performance of hybrid modulation with payload and label signals are discussed and evaluated in theory and simulation. The theoretical BER expressions of PDQ, PDQ-DB and PDQ-PPM are given with analysis method of hybrid modulation encoding in different the bit-rate ratios of payload and label. Theoretical derivation results are shown that the payload of hybrid modulation has a certain gain of receiver sensitivity than payload without label. The sizes of payload BER gain obtained from hybrid modulation are related to the different types of label. The simulation results are consistent with that of theoretical conclusions. The extinction ratio (ER) conflicting between hybrid encoding of intensity and phase types can be compromised and optimized in OLS system of hybrid modulation. The BER analysis method of hybrid modulation encoding in OLS system can be applied to other n-ary hybrid modulation or combination modulation systems.

Electron transfer driven highly valent silver for chronic wound treatment.

Although silver is widely added to various chronic wounds to kill higher concentrations (107-108 CFU mL-1) of bacteria, overdose of silver remains a major cause of diverse side effects, such as cytotoxicity and tissue and organ damage. Here we showed that reducing the dose level of silver, additionally conferring electron transfer potential, could simultaneously achieve good biocompatibility and strong bactericidal ability without introducing extra chemical residuals for chronic wound treatment. A systematic investigation demonstrated that 1 ppm trivalent silver ions performed rapid (5 min) and effective antibacterial activities against pathogens while not significantly affecting cell viability which were equivalent to 20 ppm monovalent silver ions with cytotoxicity, and accelerated the healing process and improved the tissue quality of burn wounds. The killing effect is independent of material and is mainly controlled by the electron transfer potentials of trivalent silver ions, which disrupts the electron transport of bacteria membrane respiration and leads to the death of bacteria. Together, such trivalent silver opens up new possibilities for dispelling the concern of silver usage in biosafety and provides an avenue for designing antibiotics or other biomedical applications.

Nanoparticle formation in a chemical storage room as a new incidental nanoaerosol source at a nanomaterial workplace.

Chemical storage rooms located near engineered nanomaterials (ENMs) workplaces can be a significant source of unintentional nanoaerosol generation. A new incidental nanoparticle source was identified and characterized in a chemical storage room located at an ENMs workplace. Stationary and mobile measurements using on-line instruments and chemical analysis of volatile organic compounds (VOCs) were carried out to identify the source. The number of nanoaerosols emitted from the chemical storage room was found to be several orders of magnitude higher than that existing in the ENMs workplace. VOC analysis showed that the accumulated precursors and oxygenated VOCs in the chemical storage room could be attributed to incidental particle formation via gas-to-particle conversion. We stress the importance of identification of the incidental nanoaerosols to allow characterization of the nanoaerosols at ENMs workplaces, and to estimate additional nanoaerosols exposure, which was previously unknown. Hazardous chemical substances in the workplace have been regulated in many countries; however, most of the regulations are focused on gas-phase or liquid-phase substances. The present study emphasizes the importance of secondary pollutants in particulate form that can be generated from the gas or liquid phase of hazardous chemical substances.

Small-cell lung cancer detection in never-smokers: clinical characteristics and multigene mutation profiling using targeted next-generation sequencing.

BACKGROUND: Once regarded as a smoker's disease, small-cell lung cancer (SCLC) has been occasionally detected in never-smokers as smoking rates decrease worldwide. We investigated the clinical and genetic characteristics of SCLC in never-smokers. PATIENTS AND METHODS: Patients diagnosed with SCLC were grouped into smokers and never-smokers. The clinical outcomes of the two groups were compared. For SCLC in never-smokers, somatic mutation profiling was carried out using the AmpliSeq™ Cancer Hotspot Panel v2 and semiconductor sequencing technology. Epidermal growth factor receptor (EGFR) mutation was confirmed by PNAClamp™. RESULTS: In total, 391 SCLC patients treated over a 5-year period were analyzed. Fifty patients (13%) were never-smokers. The median overall survival was 18.2 months in never-smokers and 13.1 months in smokers (P = 0.054). Never-smoking history was independently a good prognostic factor [hazard ratio = 0.645, 95% confidence interval (CI) 0.456-0.914], as were limited disease (HR = 0.372, 95% CI 0.294-0.471), and lower age (HR = 0.709, 95% CI 0.566-0.888). The objective response rates to first-line etoposide/cisplatin therapy were similar between never-smokers and smokers (75% versus 81%). Of 28 genetically evaluable never-smokers, EGFR mutations were detected in four cases (two L858R, one deletion in exon 19, and one G719A). Other mutations were in TP53 (n = 26), RB1 (n = 7), PTEN (n = 5), MET (n = 4), and SMAD4 (n = 3). CONCLUSIONS: Never-smokers with SCLC are increasingly prevalent and have a better prognosis than smokers with SCLC in Korea. Our study warrants further investigation in this group.

Enhanced performance of biodegradable poly(butylene succinate)/graphene oxide nanocomposites via in situ polymerization.

Poly(butylene succinate) (PBS)/graphene oxide (GO) nanocomposites were facilely prepared via in situ polymerization. The properties of the nanocomposites were studied using FTIR, XRD, and (1)H NMR, and the state of dispersion of GO in the PBS matrix was examined by SEM. The crystallization and melting behavior of the PBS matrix in the presence of dispersed GO nanosheets have been studied by DSC and polarized optical microscopy. Through the mechnical testing machine and DMA, PBS/GO nanocomposites with 3% GO have shown a 43% increase in tensile strength and a 45% improvement in storage modulus. This high performance of the nanocomposites is mainly attributed to the high strength of graphene oxide combined with the strong interfacial interactions in the uniformly dispersed PBS/GO nanocomposites.

Inferior paralabral ganglion cyst of the shoulder with labral tear -- a rare cause of shoulder pain.

INTRODUCTION: Paralabral ganglion cysts of the shoulder are rare, and their pathogenesis is similar to that of meniscal cysts. The paralabral cysts are most frequently reported along the posterior, superior, and anterior aspects of the glenohumeral joint and are uncommon inferiorly to the joint. These cysts rarely become evident clinically, unless they cause compression of surrounding structures, i.e. nerve. PATIENTS AND METHODS: We report a retrospective series of five patients with inferior paralabral ganglion cysts of the shoulder without compression of the surrounding nerve which were treated during the period from March 2007 to December 2009. All these patients presented with only chronic shoulder pain as their chief complaint, and preoperative MRI showed the cyst over the inferior aspect of a torn glenoid labrum. All patients were treated by arthroscopic cystic decompression with labrum repair. All patients were re-evaluated with MRI performed at an average of 15 months postoperatively. The clinical outcome, including the Constant score, was assessed for all patients at a median of 16 months postoperatively. RESULTS: All the five patients had remission of pain and were satisfied with the shoulder function. The postoperative MRI in all patients showed no labral cyst recurrence. The median Constant score improved from a preoperative level of 81.5 points to 98.0 points at last follow-up. CONCLUSION: This study demonstrates that, in the absence of any nerve compression symptoms around the shoulder joint, inferior paralabral cysts with labral tear also be considered in the differential diagnosis of chronic shoulder pain. Arthroscopic repair of the cyst with repair of the labrum can lead to the disappearance of symptoms. Knowledge of this clinical condition and its imaging features is critical for a correct diagnosis of this uncommon cause of chronic shoulder pain. LEVEL OF EVIDENCE: Level IV. Retrospective therapeutic study.

Trans-scaphoid perilunate dislocation with fractured carpal bones in a child.

Transcarpal fractures and dislocations in children are rarely reported in the orthopedics literature. This is a report of a 10-year-old boy who sustained a trans-scaphoid perilunate dislocation with fractures across the carpal structure: these included injuries to the scaphoid, capitate and triquetrum bones. Treatment consisted in a closed reduction for the dislocation and using the dorsal approach of an open reduction with internal fixation of the fractures. The injury healed well with a full return of good wrist function. This unusual pattern of injury is described so that it may be more readily appreciated in the future.

Modified Arthroscopic Double Row Repair of Partial Thickness Ttear of the Rotator Cuff Involving Articular and Bursal Side

Partial thickness of rotator cuff tears is considered as a common cause of shoulder disability. Various techniques for arthroscopic repair of partial thickness tear of rotator cuff have been reported in the literature. These techniques have addressed the articular side partial thickness cuff tear. We present an arthroscopic repair of partial thickness tear of rotator cuff involving both articular and bursal surfaces without converting into a full thickness tear. Each side of the tear was repaired with suture anchors separately

160-line multiwavelength generation of linear-cavity self-seeded Brillouin-Erbium fiber laser.

We have demonstrated a novel multiwavelength Brillouin-erbium fiber laser (BEFL), in which the Brillouin pump is self-excited within the linear cavity, instead of the injection from the external cavity or direct generation in the intracavity. By using this simple scheme, the generation of more than 160 Brillouin Stokes lines has been experimentally demonstrated, which is the largest one achieved in BEFLs to the best of our knowledge. Also, the single longitudinal mode operation and the low noise performance of output wavelength line have been confirmed. Meanwhile, the experiment demonstrates that the BEFL performs good stability on both the operating wavelengths and the output power of each wavelength.

Self-seeded multiwavelength Brillouin-erbium fiber laser.

We propose and demonstrate a self-seeded multiwavelength Brillouin-erbium fiber laser with an internally self-excited Brillouin pump, which is achieved by incorporation of a length of single-mode fiber together with a Sagnac loop mirror into a fiber ring cavity. In this simple scheme the Brillouin pump is self-excited in the fiber ring cavity and then used to seed the Brillouin multiwavelength comb in the single-mode fiber. Stable generation of more than 120 Brillouin Stokes wavelengths with relatively uniform amplitudes is demonstrated with this scheme. It is also shown that such a self-seeded Brillouin laser has good stability and repeatability.

Molecular cloning and characterization of mouse cardiac junctate isoforms.

Junctate is a newly identified integral ER/SR membrane calcium binding protein, which is an alternative splicing form of the same gene generating aspartyl beta-hydroxylase and junctin. Screening a mouse heart cDNA library using canine junctin cDNA as a probe yielded three complete mouse heart cDNAs. One of the cDNAs is homologous to the previously reported human junctate. The three mouse junctate proteins are composed of 270, 259, and 215 amino acids (we named them junctate-1, -2, and -3). The apparent molecular masses of the mouse junctates in SDS-PAGE were in the range between 40 and 53 kDa. Northern and Western blot analyses indicate that mouse junctates are expressed in heart, brain, spleen, lung, liver, kidney, and stomach, but not in skeletal muscle. The apparent molecular weights of junctates from heart and brain were somewhat different from those from the other tissues tested, suggesting that there are tissue-specific expression patterns of the different junctate isoforms. Immunohistochemical studies showed that junctates were expressed both in ventricular and atrial tissues. This is the first study that shows the presence of 3 distinct cardiac junctate isoforms expressed in various mammalian tissues.

Molecular cloning and characterization of mouse cardiac triadin isoforms.

Triadin is a ryanodine receptor and calsequestrin binding protein located in junctional sarcoplasmic reticulum of striated muscles. In the present study, mouse cardiac triadin cDNAs have been identified by cDNA library screening and RT-PCR. The deduced aa sequences show that the three isoforms consist of 277, 293 and 305 aa giving rise to the molecular weights of approximately 31,414, 33,066, and 34,328, respectively. The isoforms have identical 262 aa N-terminal sequences, whereas they have distinct C-terminal sequences. Northern blot analysis using a cDNA probe representing the N-terminal common region of triadin revealed that the mouse triadins were present both in heart and skeletal muscles. The estimated sizes of the transcripts were approximately 1.3, 4.3 and 5 kb in heart and 5, 5.5 and 7 kb in skeletal muscle. Endo H treatment and Western blot analysis of isolated mouse cardiac sarcoplasmic reticulum and in vitro translation products indicate that there are three distinct mouse cardiac triadin isoforms having molecular weights of 35, 35.5 and 40 kDa. We termed those three isoforms as mouse cardiac triadin 1, mouse cardiac triadin 2 and mouse cardiac triadin 3.