Purpose:In this phase I study (NCT01307267), we evaluated safety, pharmacokinetics, clinical activity, and pharmacodynamics of treatment with utomilumab plus rituximab in patients with relapsed/refractory follicular lymphoma (FL) and other CD20+ non-Hodgkin lymphomas (NHL). Patients and Methods:Primary objectives were to assess treatment safety and tolerability for estimating the MTD, using a modified time-to-event continual reassessment method, and selecting the recommended phase II dose (RP2D)....
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Purpose:The tumor microenvironment (TME) consists of a heterogenous cellular milieu that can influence cancer cell behavior. Its characteristics have an impact on treatments such as immunotherapy. These features can be revealed with single-cell RNA sequencing (scRNA-seq). We hypothesized that scRNA-seq analysis of gastric cancer together with paired normal tissue and peripheral blood mononuclear cells (PBMC) would identify critical elements of cellular deregulation not apparent with other approaches....
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Purpose:Most ALK-positive lung cancers will develop ALK-independent resistance after treatment with next-generation ALK inhibitors. MET amplification has been described in patients progressing on ALK inhibitors, but frequency of this event has not been comprehensively assessed. Experimental Design:We performed FISH and/or next-generation sequencing on 207 posttreatment tissue (n = 101) or plasma (n = 106) specimens from patients with ALK-positive lung cancer to detect MET genetic alterations. We...
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Purpose:Older patients with glioblastoma (GBM) are underrepresented in clinical trials. Several abbreviated and standard chemoradiotherapy regimens are advocated with no consensus on the optimal approach. Our objective was to quantitatively evaluate which of these regimens would provide the most favorable survival outcomes in older patients with GBM using a network meta-analysis. Experimental Design:MEDLINE, Embase, Google Scholar, and the Cochrane Library were searched. Patients >60 years of...
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Purpose:PARP inhibitors (PARPi) are efficacious in multiple cancers harboring germline (and possibly somatic) BRCA1/2 mutations. Acquired reversions can restore BRCA1/2 function, causing resistance to PARPi and/or platinum-based chemotherapy. The optimal method of identifying patients with germline, somatic, and/or reversion mutations in BRCA1/2 has not been established. Next-generation sequencing (NGS) of cell-free DNA (cfDNA) provides a platform to identify these three types of BRCA1/2 mutations....
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Purpose:Malignancy of cancer cells depends on the active transcription of tumor-associated genes. Recently, unique clusters of transcriptional enhancers, termed super-enhancers, have been reported to drive the expression of genes that define cell identity. In this study, we characterized specific super-enhancer–associated genes of osteosarcoma, and explored their potential therapeutic value. Experimental Design:Super-enhancer regions were characterized through chromatin immunoprecipitation sequencing...
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Purpose:Existing cell-free DNA (cfDNA) methods lack the sensitivity needed for detecting minimal residual disease (MRD) following therapy. We developed a test for tracking hundreds of patient-specific mutations to detect MRD with a 1,000-fold lower error rate than conventional sequencing. Experimental Design:We compared the sensitivity of our approach to digital droplet PCR (ddPCR) in a dilution series, then retrospectively identified two cohorts of patients who had undergone prospective plasma...
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Purpose:Patients with triple-negative breast cancer (TNBC) with homologous recombination deficient tumors achieve significantly higher pathologic complete response (pCR) rates when treated with neoadjuvant platinum-based therapy. Tumor-infiltrating lymphocytes (TIL) are prognostic and predictive of chemotherapy benefit in early stage TNBC. The relationship between TILs, BRCA1/2 mutation status, and homologous recombination deficiency (HRD) status in TNBC remains unclear. Experimental Design:We...
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Purpose:Enhanced lipogenesis and mitochondrial function are two critical metabolic characteristics in melanoma, but their crosstalk involved in tumor biology and targeted therapy remains unknown. ATP-citrate lyase (ACLY) is a crucial lipogenic enzyme that is greatly implicated in tumor development, but its role in mitochondrial function and melanoma pathogenesis has not been elucidated. Experimental Design:In vitro and in vivo functional experiments were performed to determine the effect of ACLY...
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Chimeric antigen receptor (CAR) T-cell therapy has been acclaimed as a revolution in cancer treatment following the impressive results in hematologic malignancies. Unfortunately, in patients with solid tumors, objectives responses to CAR T cells are still anecdotal, and important issues are driven by on-target but off-tumor activity of CAR T cells and by the extremely complex biology of solid tumors. Here, we will review the recent attempts to challenge the therapeutic impediments to CAR T-cell therapy...
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Matched pre-/posttreatment tissue biopsies from patients with EGFR-mutant non–small cell lung cancer demonstrate that histologic transformations, including both small-cell carcinoma and squamous transformation, are unexpectedly common among patients progressing on first-line osimertinib. The study highlights the key role of tissue testing and underscores the need for innovative therapeutic approaches to prevent, rather than treat, resistance. See related article by Schoenfeld et al., p. 2654
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PARP inhibitors (PARPi) are promising in BRCA2-altered prostate cancer. Data were presented on PARPi efficacy in prostate cancers with alterations in other DNA damage repair genes which suggest low response rates in ATM-, CHEK2-, CDK12-altered tumors and promising results in PALB2-, RAD51B-, FANCA-, and BRIP1-altered tumors. See related article by Abida et al., p. 2487
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Abstract Ibrutinib treatment has been shown to increase survival in patients with B cell malignancies. Real-life data suggest a large part of discontinuations are due to toxicities, impairing ibrutinib efficacy. We aimed to assess the impact of a pharmaceutical care program on the efficacy and safety of ibrutinib. This single-center, cohort, observational study enrolled patients with B cell malignancies. Patients were either assigned to the program or to receive usual care, based...
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Summary The risk of cancer among adults with metabolically healthy obesity (MHO) has not yet been established. We systematically searched from inception to 15 March 2020. We included prospective cohort studies that compared participants with MHO and participants with metabolically healthy non‐obesity (MHNO) for incidence of any type of cancer. Benign tumors, cancer mortality or cancer prognosis were not in the scope of our analysis. The Newcastle–Ottawa Scale was used for quality assessment. Ultimately,...
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DNA damage‐induced apoptosis suppressor promotes activation of tyrosine phosphorylation of STAT3 through their interaction. Miconazole exerts an anti–cancer effect by suppressing STAT3 activation through inhibition of DDIAS/STAT3 binding. Abstract DNA damage‐induced apoptosis suppressor (DDIAS) facilitates the survival of lung cancer by suppressing apoptosis. Moreover, DDIAS promotes tyrosine phosphorylation of signal transducer and activator of transcription 3 (STAT3) via their interaction. Here,...
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Gauri Raman Gangakhedkar, Raghbirsingh Gehdoo, Jasmeen Kaur, Sohan Lal SolankiIndian Journal of Anaesthesia 2020 64(6):529-530
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Babita Ghai, Naveen Malhotra, Sukhminder Jit Singh BajwaIndian Journal of Anaesthesia 2020 64(6):456-462 Treatment of chronic pain is an essential service. Due to lockdown, travel restrictions, social and physical distancing requirements or fear that health care facilities may be infected; patients may avoid visiting health care facilities in person. It is also imperative to decrease the risk of exposure of the health care workers (HCWs) to severe acute respiratory syndrome corona virus 2 (SARS...
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Ankur Khandelwal, Gyaninder P SinghIndian Journal of Anaesthesia 2020 64(6):544-545
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Isha Sharma, Shelly Rana, Bharti Choudhary, Tanvi Dhiman, Sheena Sharma, Mahesh KumarIndian Journal of Anaesthesia 2020 64(6):463-469 Background and Aim: Intrathecal and intravenous dexmedetomidine has been used as adjuvant in subarachnoid block [SAB]. The aim of this study was to compare the analgesic efficacy of intravenous vs intrathecal dexmedetomidine as adjuvant to intrathecal bupivacaine. Methods: Ninety patients, aged 20–60 years belonging to American Society of Anaesthesiologists (ASA)...
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Rammurthy Kulkarni, Shilpa G K BhatIndian Journal of Anaesthesia 2020 64(6):536-537
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Sumitra G Bakshi, Ajay Gawri, Amit R PanigrahiIndian Journal of Anaesthesia 2020 64(6):470-476 Background: Emergency laparotomies present a challenge in pain management given sick patients, odd timings and poor outcomes. Current recommendations favour multimodal opioid-sparing analgesia following elective laparotomies. No recommendation exists for emergency surgeries. Methodology: After approval and registration of the trial, adult patients posted for emergency laparotomy in the hospital (tertiary...
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Sarath Venugopalan, Nitu Puthenveettil, Sunil Rajan, Jerry PaulIndian Journal of Anaesthesia 2020 64(6):524-526 Gitelman syndrome is a rare autosomal recessive salt-losing disorder of renal tubules, which results in hypokalemic metabolic alkalosis. Associated hypomagnesaemia and hypocalcaemia are also seen. Gitelman syndrome is a variant of renal Bartter's syndrome. Anaesthetic management of these obstetric patients is challenging and requires a careful multidisciplinary approach. Close monitoring...
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Sonali Kaushal, Surinder Singh, Anupam SharmaIndian Journal of Anaesthesia 2020 64(6):477-482 Background and Aims: Height and weight-based formulae are used for calculation of dose of medications for caudal analgesia but these have not been compared. We compared spinal column height-based Spiegel and weight-based Takasaki and Armitage formulae for achieving maximum height of sensory neuraxial block after caudal epidural analgesia in paediatric patients. Methods: In this double-blind randomised...
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Amitraz toxicity after topical application: A rare case report with a brief review of the literature
Neeraj Kumar, Amarjeet Kumar, Abhyuday Kumar, Anil KumarIndian Journal of Anaesthesia 2020 64(6):532-534
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Zhang Jing, Yu Ling, Feng YiIndian Journal of Anaesthesia 2020 64(6):483-487 Background and Aims: Previous work shows that transcutaneous electrical stimulation (TES) has analgesic and sedative effects. However, it is unclear whether TES can affect the sedative effect of propofol or not. This study was designed to assess the effect of TES on median effective plasma concentration (Cp50) of propofol and haemodynamic changes before and after tracheal intubation. Methods: 48 patients belonging to ASA...
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Rachel C Koshy, Hally Thankamony, Jayasree Vijay, Cherian KurianIndian Journal of Anaesthesia 2020 64(6):540-541
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Deepshikha Jain, Anjum S Khan JoadIndian Journal of Anaesthesia 2020 64(6):488-494 Background: The aim was to study perioperative management in head and neck cancer, the commonest cancer in Indian men, after radiation therapy. Radiotherapy (RT) targets the tumour and the neck including the thyroid gland. RT induced physical effects (on the airway) and physiological effects (on the thyroid) impact perioperative care. Patients with RT-induced subclinical and mild clinical hypothyroidism are often...
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Ramachandran Gopinath, Sangineni K S Dhanalakshmi, Kiran Tejavath, Polapally VenuIndian Journal of Anaesthesia 2020 64(6):453-455
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Rajeeb K Mishra, Mihir P Pandia, Subodh Kumar, Gyaninder P Singh, M KalaivaniIndian Journal of Anaesthesia 2020 64(6):495-500 Background and Aims: Delayed cerebral ischaemia is one of the major contributors to morbidity in aneurysmal subarachnoid haemorrhage (aSAH). General anaesthesia (GA) in the presurgical period may have a preconditioning effect. The primary aim was to assess the effect of preoperative exposure to GA during digital subtraction angiography (DSA) on neurological outcome in patients...
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Monish S Raut, Vijay M HanjooraIndian Journal of Anaesthesia 2020 64(6):527-528
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Tasneem Dhansura, Nirbha Ghurye, Aastha Khurana, Swati Kudalkar, Yash UpadhyayIndian Journal of Anaesthesia 2020 64(6):501-506 Background and Aims: Out of hospital cardiac arrest (OHCA) is a leading cause of mortality worldwide. Increased bystander cardiopulmonary resuscitation (CPR) is observed in regions where school CPR training has been mandatory and led to reduced mortality by OHCA. We would like to explore the feasibility of teaching compression only life support (COLS) CPR to Indian school...
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Tanvi Bhargava, Abhishek Kumar, Tapas K Singh, Amit RastogiIndian Journal of Anaesthesia 2020 64(6):531-532
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Sathianarayanan Srinivasan, Rajeshwari Subramaniam, Anjolie Chhabra, Dalim K Baidya, Mahesh K Arora, Souvik Maitra, Virender K Bansal, Hemanga K BhattacharjeeIndian Journal of Anaesthesia 2020 64(6):507-512 Background and Aims: Postoperative pain following laparoscopic donor nephrectomy (LDN) is significant and no suitable analgesic technique is described. Opioid analgesia in standard doses is often suboptimal and associated with numerous adverse effects. Transversus abdominis plane (TAP) block...
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Savitri Velayudhan, Pratheeba Natrajan, Ravindra BhatIndian Journal of Anaesthesia 2020 64(6):534-536
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George J W Lin, Ying Ching Lim, Jiexun Wang, Siddiqui ShahlaIndian Journal of Anaesthesia 2020 64(6):513-516
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Ankit Sharma, Asha Tyagi, Ashana SingalIndian Journal of Anaesthesia 2020 64(6):538-539
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Polona Gams, Nenad Danojević, Marko Bitenc, Maja ŠoštaričIndian Journal of Anaesthesia 2020 64(6):516-519
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Swapnil Y ParabIndian Journal of Anaesthesia 2020 64(6):542-543
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Melissa K Stubbs, Megan A Wellbeloved, Janine C VallyIndian Journal of Anaesthesia 2020 64(6):520-523 Due to the rising caesarean section (CS) rate, there has been an increase in placenta percreta (PP) cases. Resuscitative endovascular balloon occlusion of the aorta (REBOA) use has been successful in obstetric surgery for PP. In our institution, it has been introduced for prophylactic and therapeutic management in patients with PP. In our environment, the risks, benefits, and associated cost of...
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Ramamani Mariappan, Krishnaprabhu RajuIndian Journal of Anaesthesia 2020 64(6):546-547
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Research in baboons suggests that misfolded proteins linked to Parkinson’s disease can travel from the brain to gut and vice versa – with both routes causing equal amounts of brain cell death
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Background:Although the poor prognosis and increasing incidence of pancreatic cancer highlight the need for prevention strategies, few lifestyle risk factors for pancreatic cancer have yet been identified. Soybeans contain various bioactive compounds. However, the association between soy food intake and pancreatic cancer risk remains unknown. Methods:The Japan Public Health Center–based Prospective Study is a cohort study conducted in a general Japanese population. To determine the association...
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Acrylamide is a probable human carcinogen. Aside from occupational exposures and smoking, diet is the main source of exposure in humans. We performed a systematic review of the association between estimated dietary intake of acrylamide and risk of female breast, endometrial, and ovarian cancers in nonexperimental studies published through February 25, 2020, and conducted a dose–response meta-analysis. We identified 18 papers covering 10 different study populations: 16 cohort and two case–control...
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Background:We aimed to evaluate the utility of p16/Ki-67 dual-stained cytology for triaging human papillomavirus (HPV)-positive women. Methods:HPV-positive women ages ≥ 21 years were recruited in a multicenter prospective observational study between May 2016 and May 2017. The clinical performance of dual-stained cytology, with or without HPV16/18 genotyping, was evaluated for all HPV-positive women to detect cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Results:846 HPV-positive...
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Background:Evidence suggest that diabetes and glycated hemoglobin (HbA1c) levels are associated with cancer risk. However, previous studies have been limited variably by failure to adjust for cancer-specific risk factors (e.g., body mass index), inattention to diabetes duration and use of antidiabetic medications, and failure to stratify by obesity. Methods:We examined the association between diabetes, HbA1c, and cancer risk in the UK Biobank, using data from 476,517 participants (54% women), followed...
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Background:Independent validation of risk prediction models in prospective cohorts is required for risk-stratified cancer prevention. Such studies often have a two-phase design, where information on expensive biomarkers are ascertained in a nested substudy of the original cohort. Methods:We propose a simple approach for evaluating model discrimination that accounts for incomplete follow-up and gains efficiency by using data from all individuals in the cohort irrespective of whether they were sampled...
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Background:Diabetes mellitus is known to have a negative effect on colorectal cancer survival due to hyperinsulinemia or hyperglycemia, and medications such as metformin, which targets insulin resistance and hyperinsulinemia, have a preventive effect on the risk of death. The aim of this study was to compare the risk of death among patients with colorectal cancer with diabetes with different levels of adherence to oral antidiabetics. Methods:National Health Information Database was used, which...
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Background:The association between male pattern baldness and prostate cancer has been inconsistent. We prospectively investigated the association between baldness at age 45 and prostate cancer risk in the Health Professionals Follow-up Study (HPFS), focusing on clinical and molecular markers. Methods:Baldness was self-reported on the 1992 questionnaire using the modified Norwood–Hamilton scale prior to diagnosis. We estimated HRs between baldness and prostate cancer risk among 36,760 men, with...
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Background:Low serum 25-hydroxyvitamin D [25(OH)D] concentrations in patients with colorectal cancer have been consistently associated with higher mortality in observational studies. It is unclear whether low 25(OH)D levels directly influence colorectal cancer mortality. To minimize bias, we use genetic variants associated with vitamin D levels to evaluate the association with overall and colorectal cancer–specific survival. Methods:Six genetic variants have been robustly identified to be associated...
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Background:Emerging evidence supports a role of the receptor activator of NF-B (RANK) pathway in normal mammary gland development and breast carcinogenesis. Osteoprotegerin (OPG) is the endogenous decoy receptor for RANK-ligand (RANKL), which inhibits RANK-signaling. Whether OPG may be a biomarker of breast cancer risk remains unclear. Methods:We evaluated the association between plasma OPG and breast cancer risk in a case (n = 297)–control (n = 297) study nested within the Nurses' Health Study...
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Background:Vitamin D status may be an important determinant of health-related quality of life of colorectal cancer survivors. The current study investigated longitudinal associations between serum 25-hydroxyvitamin D3 (25OHD3) concentrations and quality of life in stage I–III colorectal cancer survivors up to 2 years after treatment. Methods:Patients with colorectal cancer (n = 261) were included upon diagnosis. Home visits (including blood sampling) were performed at diagnosis and at 6 weeks,...
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Background:The underlying etiology of colorectal cancer includes both genetic variation and environmental exposures. The main aim of this study was to search for interaction effects between well-established environmental risk factors and published common genetic variants exerting main effects on colorectal cancer risk. Methods:We used a two-phase approach: (i) discovery phase (2,652 incident colorectal cancer cases and 10,608 controls from UK Biobank) and (ii) validation phase (1,656 cases and...
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