Rosai-Dorfman disease in a symptomatic elderly man.

An 81-year-old man presented with anemia, fatigue, weight loss, and recurrent urinary tract infections and was found to have diffuse large adenopathy and infiltrating renal masses. Surgical excision of a lymph node and histologic evaluation led to the diagnosis of Rosai-Dorfman disease, a rare histioproliferative condition that classically presents with enlarged cervical lymph nodes bilaterally. It also can involve additional nodal chains and/or have extranodal manifestations. The condition can self-resolve or have periods of remission and reactivation.

Lenvatinib plus pembrolizumab in patients with either treatment-naive or previously treated metastatic renal cell carcinoma (Study 111/KEYNOTE-146): a phase 1b/2 study.

BACKGROUND: Despite advances in the first-line treatment of metastatic renal cell carcinoma (RCC), there is an unmet need for options to address disease progression during or after treatment with immune checkpoint inhibitors (ICIs). Pembrolizumab and lenvatinib are active as monotherapies in RCC; thus, we aimed to evaluate the combination of lenvatinib plus pembrolizumab in these patients. METHODS: We report results of the metastatic RCC cohort from an open-label phase 1b/2 study of lenvatinib plus pembrolizumab in patients aged at least 18 years with selected solid tumours and an Eastern Cooperative Oncology Group performance status of 0-1. Oral lenvatinib at 20 mg was given once daily along with intravenous pembrolizumab at 200 mg once every 3 weeks. Patients remained on study drug treatment until disease progression, development of unacceptable toxicity, or withdrawal of consent. Efficacy was analysed in patients with clear cell metastatic RCC receiving study drug by previous therapy grouping: treatment naive, previously treated ICI naive (previously treated with at least one line of therapy but not with an anti-PD-1 or anti-PD-L1 ICI), and ICI pretreated (ie, anti-PD-1 or anti-PD-L1) patients. Safety was analysed in all enrolled and treated patients. The primary endpoint was the objective response rate at week 24 per immune-related Response Evaluation Criteria In Solid Tumors (irRECIST) by investigator assessment. This trial is registered with ClinicalTrials.gov (NCT02501096) and with the EU Clinical Trials Register (EudraCT2017-000300-26), and is closed to new participants. FINDINGS: Between July 21, 2015, and Oct 16, 2019, 145 patients were enrolled in the study. Two patients had non-clear cell RCC and were excluded from the efficacy analysis (one in the treatment-naive group and one in the ICI-pretreated group); thus, the population evaluated for efficacy comprised 143 patients (n=22 in the treatment-naive group, n=17 in the previously treated ICI-naive group, and n=104 in the ICI-pretreated group). All 145 enrolled patients were included in the safety analysis. The median follow-up was 19·8 months (IQR 14·3-28·4). The number of patients with an objective response at week 24 by irRECIST was 16 (72·7%, 95% CI 49·8-89·3) of 22 treatment-naive patients, seven (41·2%, 18·4-67·1) of 17 previously treated ICI-naive patients, and 58 (55·8%, 45·7-65·5) of 104 ICI-pretreated patients. Of 145 patients, 82 (57%) had grade 3 treatment-related adverse events and ten (7%) had grade 4 treatment-related adverse events. The most common grade 3 treatment-related adverse event was hypertension (30 [21%] of 145 patients). Treatment-related serious adverse events occurred in 36 (25%) patients, and there were three treatment-related deaths (upper gastrointestinal haemorrhage, sudden death, and pneumonia). INTERPRETATION: Lenvatinib plus pembrolizumab showed encouraging antitumour activity and a manageable safety profile and might be an option for post-ICI treatment of metastatic RCC. FUNDING: Eisai and Merck Sharp & Dohme.

Clinical outcomes in 995 unselected real-world patients treated with an ultrathin biodegradable polymer-coated sirolimus-eluting stent: 12-month results from the FLEX Registry.

OBJECTIVES: To evaluate, in the FLEX Registry, clinical outcomes of an ultrathin (60 µm) biodegradable polymer-coated Supraflex sirolimus-eluting stent (SES) for the treatment of coronary artery disease. Additionally, to determine the vascular response to the Supraflex SES through optical coherence tomography (OCT) analysis. SETTING: Multicentre, single-arm, all-comers, observational registry of patients who were treated with the Supraflex SES, between July 2013 and May 2014, at nine different centres in India. PARTICIPANTS: 995 patients (1242 lesions) who were treated with the Supraflex SES, between July 2013 and May 2014, at nine different centres in India. A total of 47 participants underwent OCT analysis at 6 months' follow-up. INTERVENTIONS: Percutaneous coronary intervention with Supraflex SES, PRIMARY AND SECONDARY OUTCOME MEASURES: The primary endpoint-the rate of major adverse cardiac events (defined as a composite of cardiac death, myocardial infarction (MI), target lesion revascularisation (TLR))-was analysed during 12 months. RESULTS: At 12 months, the primary endpoint occurred in 36 (3.7%) of 980 patients, consisting of 18 (1.8%) cardiac deaths, 16 (1.6%) MI, 7 (0.7%) TLR and 2 (0.2%) cases of non-target lesion target vessel revascularization. In a subset of 47 patients, 1227 cross-sections (9309 struts) were analysed at 6 months by OCT. Overall, a high percentage of struts was covered (98.1%), with a mean neointimal thickness of 0.13 ± 0.06 µm. CONCLUSIONS: The FLEX Registry evaluated clinical outcomes in real-world and more complex cohorts and thus provides evidence that the Supraflex SEX can be used safely and routinely in a broader percutaneous coronary intervention population. Also, the Supraflex SES showed high percentage of stent strut coverage and good stent apposition during OCT follow-up.

Accessory pancreatic lobe with gastric duplication cyst: diagnostic challenges of a rare congenital anomaly.

Reports of combined congenital abnormalities of gastric duplication cysts and accessory pancreatic lobes are rarely reported. Patients with such anomalies may require appropriate surgical intervention tailored to the individual patient for complete cure. A multimodality diagnostic approach using ultrasonography, CT and MRI is useful for appreciation of the relevant anatomy of the congenital abnormality and for proper surgical planning. We present a case of a gastric duplication cyst with accessory pancreatic lobe and ectopic pancreatic rest in a 5-year-old child presenting with symptoms of recurrent pancreatitis.

Paclitaxel formulations: challenges and novel delivery options.

Paclitaxel (PTX), a taxane plant product, is one of the most effective broad-spectrum anti-cancer agents and approved for the treatment of a variety of cancers including ovarian, breast, lung, head and neck as well as Kaposi's sarcoma. Poor aqueous solubility and serious side effects associated with commercial preparation of PTX (Taxol®) triggered the development of alternative PTX formulations. Over past three decades, plethora of research work has been published towards the development of cremophor free and efficient formulations. Various nanocarrier systems including nanoparticles, liposomes, micelles, bioconjugates and dendrimers have been employed in order to improve PTX solubility and eliminate undesired side effects. These nanocarriers offer the advantage of high degree of encapsulation and cellular uptake, escape from elimination by P-glycoprotein (P-gp) mediated efflux, and can be explored for targeted drug delivery. The potential of these nanocarriers is reflected by the fact that various nanocarriers of PTX are in different stages of clinical trials and a few have already been commercialized including Abraxane®, Lipusu and Genexol PM®. This review focuses on the various challenges associated with PTX formulation development, limitations of existing formulations and novel approaches for the development of alternative formulations for PTX and also highlights the development of novel formulations in clinical settings.

Development and evaluation of paclitaxel loaded PLGA:poloxamer blend nanoparticles for cancer chemotherapy.

This investigation described the development of novel PLGA:poloxamer blend nanoparticles for intravenous administration of paclitaxel in order to limit the cremophor-associated adverse effects. The developed formulation was well-characterized using various techniques including scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy and differential scanning calorimetry. The nanoparticles had an average particle size around 180nm and zeta potential of -22.7mV. The in vitro release study of nanoparticles exhibited biphasic release pattern. The non-hemolytic potential of the nanoparticles indicated the suitability of the developed formulation for intravenous administration. The PLGA:poloxamer blend nanoparticles showed significantly improved cytotoxicity in cell lines (MCF-7 and Colo-205), as compared to free drug. Further, the developed formulation was stable under the accelerated storage conditions. In conclusion, the results indicated that the developed polymeric formulation is a novel and potential alternative for the paclitaxel delivery.

Patient profile and results of percutaneous transvenous mitral commissurotomy in mitral restenosis following prior percutaneous transvenous mitral commissurotomy vs surgical commissurotomy.

BACKGROUND: Patients with mitral restenosis who have undergone prior PTMC or surgical commissurotomy have increased. Predictors of outcome of repeat PTMC in either subgroup of patients may be different. AIMS AND OBJECTIVES: Aim was to assess and compare the immediate results of PTMC in patients who had undergone a prior PTMC or surgical commissurotomy. METHODS AND RESULTS: This is a single center, prospective, open label study. Of 70 patients in study, 44 (62.85%) patients had prior history of PTMC and 26 (37.15%) had prior surgical commissurotomy (closed/open). Average time from the initial procedure was 8.88 ± 5.36 years overall, 6.75 ± 3.38 for patients with prior PTMC and 16.73 ± 3.67 for patients with prior surgical commissurotomy. Prior PTMC group had 75% female, patients with prior surgical commissurotomy were older (44 ± 7 vs 33.57 ± 9.1 years, p = 0.001), had higher NYHA class (III/IV in100% vs 86.36%, p = 0.006.), higher atrial fibrillation (73.1% vs 25% p < 0.0001) and higher Wilkins' score (>8 in 88.46% vs 68.18%, p = 0.05). Successful PTMC was lower (65.4% vs 84.1%) in patients with prior surgical commissurotomy, though statistically not significant (p = 0.07). After PTMC, mitral valve area, PA systolic pressure, LA mean pressure and trans-mitral gradient were similar. Post procedure complications were not different in both the groups. CONCLUSION: PTMC for mitral restenosis in patients with prior surgical valvotomy is as effective as in patients with prior PTMC despite older age, higher NYHA class, higher Wilkins score and atrial fibrillation and can be considered in all patients with restenosis irrespective of the type of past procedures done.

Spontaneous cholecystocolic fistula: case report.

Cholecystocolic fistula is a rare billiary-enteric fistula with variable clinical presentation. Despite modern diagnostic tool a high degree of suspicion is required to diagnose it preoperatively. These fistulae are treated by open as well as laparoscopic surgery, with no difference in intraoperative and postoperative complications. We are describing a 50-year-old female patient with the diagnosis of chronic cholecystitis with cholelithiasis, which was investigated with routine lab investigations, and abdominal ultrasonography but none of these gave us any clue to the presence of fistula, were discovered incidentally during an open surgery and were appropriately treated.

Novel atherosclerotic risk factors and angiographic profile of young Gujarati patients with acute coronary syndrome.

OBJECTIVES: In this study we aimed to analyse the frequency of atherosclerotic risk factors with focus to novel risk factors for coronary artery disease and angiographic profile in young (≤ 40 years) acute coronary syndrome (ACS) patient with healthy controls in Gujarat, India. METHODS: Between January 2008 and December 2012, 109 consecutive young patients aged ≤ 40 years old, diagnosed to have ACS were included in the study. All ACS patients underwent diagnostic coronary angiography. An equivalent age and sex matched population without coronary disease with similar risk factors without tobacco considered a control group. All angiographic patients were evaluated for conventional risk factors for coronary artery disease like diabetes mellitus, hypertension, smoking, obesity as well as novel atherogenic risk factors like high sensitivity C-reactive protein (Hs-CRP), Lipoprotein(a) [LP(a)], homocysteine, apolipoprotein A1 (ApoA1) and B (ApoB). RESULT: In a study group, out of 109 young patients, 90 (82.6%) patients were presented to our hospital as ST-segment elevation myocardial infarction (STEMI), 10 (9.2%) presented as known non-ST-elevation myocardial infarction (NSTEMI) and 9 (8.3%) presented as unstable angina (UA). Serum cholesterol, triglycerides, LDL, LP(a) and lipid tetrad index were significantly higher in the study group whereas the HDL levels significantly lower as compared to the control group. CONCLUSION: A quite common risk factors of premature CAD are smoking, high Hs-CRP, high LP(a), hyperhomocysteinaemia and positive family history in the young ACS. Most common presentation of ACS in young was STEMI. On angiography, single vessel involvement was the most common finding.

Biodegradable-polymer-based, sirolimus-eluting Supralimus stent: 6-month angiographic and 30-month clinical follow-up results from the series I prospective study.

AIMS: There have been recent concerns regarding the long-term safety of the first generation of drug-eluting stents, which utilised a permanent polymer coating for drug delivery. SERIES I is a prospective, non-randomised, first-in-man open label study with the biodegradable polymer-based Supralimus sirolimus eluting stent (Sahajanand Medical Technologies Pvt. Ltd, India) for the treatment of patients with coronary artery lesions. METHODS AND RESULTS: One hundred patients were treated with 126 Supralimus stents (mean lesion length 10.5 +/- 4.3 mm, mean reference vessel diameter 2.66 +/- 0.62 mm). The pre-specified primary endpoint was angiographic binary in-stent restenosis at six months. Secondary endpoints were device-orientated major adverse clinical events (MACE; defined as a composite of cardiac death, nonfatal myocardial infarction [Q-wave and Non-Q wave], or clinically-justified target vessel revascularisation) at 30 days, nine months and 30 months. Angiographic follow-up in a pre-specified subgroup of 60 patients at six months showed binary angiographic restenosis rates of 0% (in-stent) and 1.7% (in-segment). The in-stent late loss was 0.09 +/- 0.37 mm. MACE rates were 0% after one month, 6% at 9-month follow-up and 7% after 30 months follow-up. CONCLUSIONS: The biodegradable-polymer-based sirolimus-eluting stent (Supralimus) is effective in inhibiting neointimal hyperplasia.