Comparative effectiveness of intensity modulated radiation therapy to 3-dimensional conformal radiation in locally advanced lung cancer: pathological and clinical outcomes.

OBJECTIVE: Intensity-modulated radiotherapy (IMRT) has better normal-tissue sparing compared with 3-dimensional conformal radiation (3DCRT). We sought to assess the impact of radiation technique on pathological and clinical outcomes in locally advanced non-small cell lung cancer (LANSCLC) treated with a trimodality strategy. METHODS: Retrospective review of LANSCLC patients treated from August 2012 to August 2018 at Sheba Medical Center, Israel. The trimodality strategy consisted of concomitant chemoradiation to 60 Gray (Gy) followed by completion surgery. The planning target volume (PTV) was defined by co-registered PET/CT. Here we compare the pathological regression, surgical margin status, local control rates (LC), disease free (DFS) and overall survival (OS) between 3DCRT and IMRT. RESULTS: Our cohort consisted of 74 patients with mean age 62.9 years, male in 51/74 (69%), adenocarcinoma in 46/74 (62.1%), stage 3 in 59/74 (79.7%) and chemotherapy in 72/74 (97.3%). Radiation mean dose: 59.2 Gy (SD ± 3.8). Radiation technique : 3DCRT in 51/74 (68.9%), IMRT in 23/74 (31%). Other variables were similar between groups.Major pathological response (including pathological complete response or less than 10% residual tumor cells) was similar: 32/51 (62.7%) in 3DCRT and 15/23 (65.2%) in IMRT, p=0.83. Pathological complete response (pCR) rates were similar: 17/51 (33.3%) in 3DCRT and 8/23 (34.8%) in IMRT, p=0.9. Surgical margins were negative in 46/51 (90.1%) in 3DCRT vs. 17/19 (89.4%) in IMRT (p=1.0).The 2-year LC rates were 81.6% (95% CI 69-89.4%); DFS 58.3% (95% CI 45.5-69%) and 3-year OS 70% (95% CI57-80%). Comparing radiation techniques, there were no significant differences in LC (p=0.94), DFS (p=0.33) and OS (p=0.72). CONCLUSION: When used to treat LANSCLC in the neoadjuvant setting, both IMRT and 3DCRT produce comparable pathological and clinical outcomes. ADVANCES IN KNOWLEDGE: This study validates the real-world effectiveness of IMRT compared to 3DCRT

"The fruits of independence": Satyajit Ray, Indian nationhood and the spectre of empire

Challenging the longstanding consensus that Satyajit Ray's work is largely free of ideological concerns and notable only for its humanistic richness, this article shows with reference to representations of British colonialism and Indian nationhood that Ray's films and stories are marked deeply and consistently by a distinctively Bengali variety of liberalism. Drawn from an ongoing biographical project, it commences with an overview of the nationalist milieu in which Ray grew up and emphasizes the preoccupation with colonialism and nationalism that marked his earliest unfilmed scripts. It then shows with case studies of Kanchanjangha (1962), Charulata (1964), First Class Kamra (First-Class Compartment, 1981), Pratidwandi (The Adversary, 1970), Shatranj ke Khilari (The Chess Players, 1977), Agantuk (The Stranger, 1991) and Robertsoner Ruby (Robertson's Ruby, 1992) how Ray's mature work continued to combine a strongly anti-colonial viewpoint with a shifting perspective on Indian nationhood and an unequivocal commitment to cultural cosmopolitanism. Analysing how Ray articulated his ideological positions through the quintessentially liberal device of complexly staged debates that were apparently free, but in fact closed by the scenarist/director on ideologically specific notes, this article concludes that Ray's reputation as an all-forgiving, ‘everybody-has-his-reasons’ humanist is based on simplistic or even tendentious readings of his work

Study of the effect of the herbal composition SR2004 on hemoglobin A1c, fasting blood glucose, and lipids in patients with type 2 diabetes mellitus

Background: Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by raised blood glucose levels and peripheral insulin resistance. It is an increasingly prevalent global healthcare concern. Conventional treatment options are limited and in this context, there is renewed interest in evaluating the clinical and biological effects of traditional therapies. We assess the effect of a new herbal composition SR2004 on the hemoglobin A1c (HbA1c), fasting blood glucose, and lipid profiles of patients with T2DM. Methods: This is a single center, unblinded, prospective interventional study conducted in Israel. The composition SR2004 includes Morus alba, Artemisia dracunculus, Urtica dioica, Cinnamomum zeylanicum, and Taraxacum officinale. One hundred and nineteen patients with diagnosed T2DM were enrolled and received SR2004 in addition to their usual medications. HbA1c, fasting blood glucose, and lipid profiles at 12 weeks were compared with baseline. In addition, the tolerability and side effects of SR2004 were recorded. Results: One hundred and three patients completed 12 weeks of follow-up (87%) and were included in the results. At 12 weeks, HbA1c reduced from 9.0% to 7.1% (22%; p < 0.0001), mean blood glucose decreased from 211 mg/dL to 133 mg/dL (37% reduction; p < 0.0001), mean total cholesterol to 185 mg/dL (13% reduction; p < 0.01) and mean serum triglycerides to160 mg/dL (a reduction of 40% from baseline; p < 0.001). Twelve patients (12%) had no response with SR2004 supplementation. In addition, of thirteen patients who took insulin at baseline, five required only oral hypoglycemics and another five reduced their daily insulin requirements by 30% at 12 weeks. Clinical observations included improvements in vasculopathy, including reversal of established retinopathic changes in two patients.No major adverse effects were observed, with minor abdominal symptoms reported in sixteen patients (16%). Conclusion: SR2004 supplementation significantly reduced HbA1c, blood glucose, and lipids with good tolerability and no observed adverse interactions with conventional medications. Some interesting findings relating to the reversal of microvascular phenomena warrant further research to elucidate the mechanisms of action of this novel composition. Keywords: Glucose, Herbal, Lipids, Retinopathy, Type 2 diabetes mellitu

Unimodality and Multimodality Cryodebridement for Airway Obstruction. A Single-Center Experience with Safety and Efficacy

Rationale: Cryodebridement (CD) refers to the removal of obstructive material from the lumen of the tracheobronchial tree by freezing with a cryoprobe, which is usually inserted through a flexible bronchoscope. This method of achieving instant recanalization of airways has been established for over 20 years, but published experience comprises limited case series. Objectives: This study describes a single large-volume referral center experience, including clinical outcomes and safety profile. Methods: Electronic medical records of 156 patients who underwent bronchoscopic CD between December 2007 and March 2012 as the primary method to relieve airway obstruction were reviewed retrospectively. Measurements and Main Results: The most frequent cause of airway obstruction was malignancy (n = 88), with non–small-cell lung cancer and metastatic renal cell carcinoma being the most common etiologies. The site of obstruction was localized to the central airways in 63 patients (40%) and the distal airways in 44 patients (28%), and it was diffuse in 49 patients (32%). Bronchoscopic airway patency was achieved in 95% of patients, with the highest success rates found in those with obstruction localized in the central airways. Improvement in symptoms occurred in 118 (82%) of 144 symptomatic patients. Serious complications were reported in 17 patients (11%) and included respiratory distress, severe bleeding, airway injury, and hemodynamic instability. All patients responded to treatment, and no intra- or postoperative deaths were reported. Conclusions: CD, when used alone or in combination with other endoscopic treatment modalities, appears to be safe and effective in treating endoluminal airway obstruction

The inhibitor apoptosis protein antagonist Debio 1143 Is an attractive HIV-1 latency reversal candidate.

Antiretroviral therapy (ART) suppresses HIV replication, but does not cure the infection because replication-competent virus persists within latently infected CD4+ T cells throughout years of therapy. These reservoirs contain integrated HIV-1 genomes and can resupply active virus. Thus, the development of strategies to eliminate the reservoir of latently infected cells is a research priority of global significance. In this study, we tested efficacy of a new inhibitor of apoptosis protein antagonist (IAPa) called Debio 1143 at reversing HIV latency and investigated its mechanisms of action. Debio 1143 activates HIV transcription via NF-kB signaling by degrading the ubiquitin ligase baculoviral IAP repeat-containing 2 (BIRC2), a repressor of the non-canonical NF-kB pathway. Debio 1143-induced BIRC2 degradation results in the accumulation of NF-κB-inducing kinase (NIK) and proteolytic cleavage of p100 into p52, leading to nuclear translocation of p52 and RELB. Debio 1143 greatly enhances the binding of RELB to the HIV-1 LTR. These data indicate that Debio 1143 activates the non-canonical NF-kB signaling pathway by promoting the binding of RELB:p52 complexes to the HIV-1 LTR, resulting in the activation of the LTR-dependent HIV-1 transcription. Importantly, Debio 1143 reverses viral latency in HIV-1 latent T cell lines. Using knockdown (siRNA BIRC2), knockout (CRIPSR NIK) and proteasome machinery neutralization (MG132) approaches, we found that Debio 1143-mediated HIV latency reversal is BIRC2 degradation- and NIK stabilization-dependent. Debio 1143 also reverses HIV-1 latency in resting CD4+ T cells derived from ART-treated patients or HIV-1-infected humanized mice under ART. Interestingly, daily oral administration of Debio 1143 in cancer patients at well-tolerated doses elicited BIRC2 target engagement in PBMCs and induced a moderate increase in cytokines and chemokines mechanistically related to NF-kB signaling. In conclusion, we provide strong evidences that the IAPa Debio 1143, by initially activating the non-canonical NF-kB signaling and subsequently reactivating HIV-1 transcription, represents a new attractive viral latency reversal agent (LRA)

Tunneled Pleural Catheter Placement with and without Talc Poudrage for Treatment of Pleural Effusions Due to Congestive Heart Failure

RATIONALE There is a paucity of evidence regarding the role of tunneled pleural catheters in pleural effusions caused by congestive heart failure that is refractory to medical management. OBJECTIVES: The aim of this study was to assess the feasibility of tunneled pleural catheter drainage for treatment of refractory pleural effusions associated with congestive heart failure, either when used alone or with concomitant talc pleurodesis performed during thoracoscopy. METHODS: This was a retrospective cohort study. We identified patients with congestive heart failure and recurrent symptomatic pleural effusions who were treated between 2005 and 2015 by placement of a tunneled pleural catheter. Patients underwent either thoracoscopy followed by talc poudrage and pleural catheter placement (group 1) or catheter insertion alone (group 2). MEASUREMENTS AND MAIN RESULTS: Forthy-three catheters were inserted in 36 patients, with 15 placed in group 1 and 28 in group 2. Successful pleurodesis was seen in 80% in group 1 and 25% in group 2. The median time of catheter placement was 11.5 days in group 1 and 66 days in group 2. There was a significant decrease in hospital admissions and pleural interventions after catheter placement compared with before insertion (P < 0.05). CONCLUSIONS: This single-center, retrospective study demonstrated the feasibility of catheter placement used alone or with talc poudrage for the treatment of refractory pleural effusions associated with congestive heart failure. The addition of talc poudrage might increase the pleurodesis rate and reduce the days to catheter removal in highly selected patients. Prospective studies on a larger number of patients are warranted to verify the safety and efficacy of this intervention

Referral rates and barriers to lung transplantation based on pulmonary function criteria in interstitial lung diseases: a retrospective cohort study

Background: Interstitial lung diseases (ILD) unresponsive to medical therapy often require lung transplantation (LTx), which prolongs quality of life and survival. Ideal timing for referral for LTx remains challenging, with late referral associated with significant morbidity and mortality. Among other criteria, patients with ILD should be considered for LTx if forced vital capacity (FVC) is less than 80% or diffusion capacity for carbon monoxide (DLCO) is less than 40%. However, data on referral rates are lacking. Objectives: To evaluate referral rates for LTx based on pulmonary function tests (PFTs) and identify barriers associated with non-referral. Design: A single-center retrospective cohort study. Methods: The study consisted of ILD patients who performed PFT between 2014 and 2020. Patients with FVC < 80% or a DLCO < 40% were included in the study. Patients with absolute contraindications to LTx were excluded. Referral rates were computed, and a comparison was made between referred and non-referred subjects. Results: Out of 114 ILD patients meeting criteria for referral to LTx, 35 were referred (30.7%), and 7 proceeded to undergo LTx. Median time from PFT to referral for assessment was 255 days [interquartile range (IQR) 35–1077]. Median time from referral to LTx was 89 days (IQR 59–143). Referred patients were younger ( p  = 0.003), had lower FVC ( p  < 0.001), DLCO ( p  < 0.001), and a higher rate of pulmonary hypertension ( p  = 0.04). Relatively better PFT, and older age, were significantly associated with non-referral of patients. Conclusion: There is under-referral of ILD patients who are eligible for LTx, which is associated with severe disease and missed opportunities for LTx. Further research is required to validate these findings

Virtual reality utilization for left atrial appendage occluder device size prediction

Aim: To explore the feasibility and accuracy of virtual reality (VR) derived from cardiac computed angiography (CCTA) data to predict left atrial appendage occlusion (LAAO) device size. Method: Retrospective data of patients who underwent LAAO according to clinical indication were reviewed; all patients underwent a pre-procedural CCTA. Measurements of the left atrial appendage (LAA) orifice diameters by CCTA, VR, and transesophageal echocardiography (TEE) (acquired during the procedure) were compared to the implanted device size. The LAA perimeter was calculated using the Ramanujan approximation. Statistical analyses included Lin's Concordance Correlation Coefficient (ρc), the mean difference, and the mean square error (MSE). Results: The sample was composed of 20 patients (mean age 75.7 ± 7.5 years, 60% males) who underwent successful LAAO insertion (ACP™ N = 8, Watchman™ N = 12). The CCTA, VR, and TEE maximal diameter ρc was 0.52, 0.78 and 0.60, respectively with mean differences of +0.92 ± 4.0 mm, −1.12 ± 2.3 mm, and −3.45 ± 2.69 mm, respectively. The CCTA, VR, and TEE perimeter calculations ρc were 0.49, 0.54, and 0.39 respectively with mean differences of +4.69 ± 11.5 mm, −9.88 ± 8.0 mm, and −16.79 ± 7.8 respectively. Discussion: A VR visualization of the LAA ostium in different perspectives allows for a better understanding of its funnel-shaped structure. VR measurement of the maximal ostium diameter had the strongest correlation with the diameter of the inserted device. VR may thus provide new imaging possibilities for the evaluation of complex pre-procedural structures such as the LAA