Characteristics & outcomes of cancer patients with COVID-19: A multicentre retrospective study from India.

Background & objectives: High mortality has been observed in the cancer population affected with COVID-19 during this pandemic. We undertook this study to determine the characteristics and outcomes of cancer patients with COVID-19 and assessed the factors predicting outcome. Methods: Patients of all age groups with a proven history of malignancy and a recent diagnosis of SARS-CoV-2 infection based on nasal/nasopharyngeal reverse transcriptase (RT)-PCR tests were included. Demographic, clinical and laboratory variables were compared between survivors and non-survivors groups, with respect to observed mortality. Results: Between May 11 and August 10, 2020, 134 patients were included from the three centres and observed mortality was 17.1 per cent. The median age was 53 yr (interquartile range 39-61 yr) and thirty four patients (25%) were asymptomatic. Solid tumours accounted for 69.1 per cent and breast cancer was the most common tumour type (20%). One hundred and five patients (70.5%) had received chemotherapy within the past four weeks and 25 patients (19.3%) had neutropenia at presentation. On multivariate analysis, age [odds ratio (OR) 7.99 (95% confidence interval [CI] 1.18-54.00); P=0.033], haemoglobin [OR 6.28 (95% CI 1.07-37.04); P=0.042] neutrophil-lymphocyte ratio [OR 12.02 (95% CI 2.08-69.51); P=0.005] and baseline serum albumin [OR 18.52 (95% CI 2.80-122.27); P=0.002], were associated with higher mortality. Recent chemotherapy, haematological tumours type and baseline neutropenia did not affect the outcome. Interpretation & conclusions: Higher mortality in moderate and severe infections was associated with baseline organ dysfunction and elderly age. Significant proportion of patients were asymptomatic and might remain undetected.

Spontaneous pulmonary arterial embolization: A rare complication of the silicon-based peripherally inserted central venous catheter (PICC).

Peripherally inserted central catheters (PICC) are widely used in oncology for administration of chemotherapy. However, sometimes there may be complications associated with them such as infections, thrombosis and rarely fracture of catheter and embolization of the catheter fragments. Here we report a case of 59-year old gentleman with locally advanced carcinoma of head of pancreas, who had spontaneous fracture of a silicon based PICC and later migration of the catheter fragment through the heart and further into the right pulmonary arterial system. The embolized catheter fragment was retrieved through a vascular snare from the right femoral venous route. This case highlights the fact that silicon PICCs are fragile and have a high risk of spontaneous dislodgement and should be replaced by better alternative polyurethane PICCs.

PARP inhibitors in hereditary breast and ovarian cancer and other cancers: A review.

There has been a paradigm shift in the management of cancer, with the immense progress in cancer genomics. More and more targeted therapies are becoming available by the day and personalized medicine is becoming popular with specific drugs being designed for selected subgroups of patients. One such new class of targeted drugs in the armamentarium is Poly ADP Ribose Polymerase (PARP) inhibitors (PARPi), which inhibit the enzyme PARP, thus interfering with DNA repair. This strategy utilizes a pre-existing genomic lesion in tumors with homologous recombination repair defects (including BRCA mutations), weakening tumor cells further by blocking the alternate pathway of DNA repair. In this review, we discuss in detail, the evolution, genetics, mechanism of action, mechanism of resistance, indications of use of PARP inhibitors, as well as combination with other agents and future directions.

Adjunct yoga therapy: Influence on heart rate variability in major depressive disorder - A randomized controlled trial.

HRV is inversely proportional to severity of depression. Effect of 12-weeks adjunct yoga therapy on HRV in patients with MDD was assessed through a randomized controlled trial. Sixty-eight subjects (40 females) with mean age 31.58 ± 8.79 years, scoring ≥ 18 on HDRS were randomized to either (YG; n = 35) or (WG; n = 33). Linear mixed model analysis showed no significant difference between groups. On comparing change in mean percentage, substantial more decrease could be elicited only for LF/HF ratio in YG compared to WG, while being comparable for other variables across the groups. Findings suggest Yoga therapy may help in bringing parasympathetic dominance in patients with MDD.

Multiple-parallel-protease digestion coupled with high-resolution mass spectrometry: An approach towards comprehensive peptide mapping of therapeutic mAbs.

Therapeutic monoclonal antibodies (mAbs) are structurally large and complex molecules. To be safe and efficacious, a biosimilar mAb must show high similarity to its reference product in Critical Quality Attributes (CQA). mAbs are highly sensitive to protein expression, production, manufacturing, supply chain, and storage conditions. All these factors make biosimilar mAbs intrinsically susceptible for variability during production. Accordingly, several lots of references and tests are required to establish the biosimilarity of a test mAb. The primary structure is a CQA of a mAb affecting its safety and efficacy. Here, we apply peptide mapping as an analytical method to decipher the primary structure and associated modifications for a quick quality assessment of TrastuzumAb and RituximAb innovator and biosimilar. A multiple-parallel-protease digestion strategy followed by high-resolution mass spectrometric analysis consistently achieved 100% sequence coverage along with reliable detection of post-translational modifications. Additionally, the use of supporting methods such as intact mass analysis and circular dichroism helped us to decipher the primary and higher order structures of these mAbs. We identify discernible variations in the profile of the innovator and biosimilar mAbs and validate the method for quick yet deep comparability analysis of the primary structure of biosimilar mAbs sold in the market. SIGNIFICANCE: Peptide mapping using bottom-up approach is one of the most common methods for the characterization of therapeutic monoclonal antibodies. Herein, we describe a multi-parallel-protease digestion strategy using a combination of five different proteases followed by high-resolution mass spectrometric analysis with TrastuzumAb and RituximAb as an example. This resulted in a comprehensive identification of peptides with increased reliability and identification of different PTMs. Additional supporting orthogonal methods like intact mass and higher-order structure analysis helped evaluate broader conformational properties.

Extranodal NK-T Cell Lymphoma, Nasal Type: Retrospective Analysis of Real-World Data.

Peripheral T cell lymphomas constitute nearly 15% of all cases on non-Hodgkin lymphoma. Of these, NK-T cell lymphoma nasal type is a rare and aggressive form. We present our experience of 16 patients of NK/T cell lymphoma which constituted approximately 1% of all lymphoma (N = 1590) cases treated at our center. Male to female ratio was 4.3:1. Median age of presentation was 42 years. Early Stage patients (n = 11) were treated with DeVIC regimen (n = 10) and SMILE (n = 1) chemotherapy and RT to all the patients. Advanced stage patients were treated with SMILE regimen (n = 4) and ICE and local RT (n = 1) with one treatment related mortality. The presence of B-symptoms adversely affected survival. The estimated median PFS and OS were 39 and 49 months respectively. Overall survival was not reached in Limited Stage patients (stage 1 and 2) and 8 months in patients with advanced stage (stage IV) (p = 0.001). According to the new CSWOG staging (retrospectively applied), comparing the Limited versus Extensive Stage, the earlier group has a significantly better estimated PFS (p = 0.020) and OS (p = 0.007). ENKTL is a rare malignancy with aggressive course. B-symptoms portend a poor prognosis to patients with this aggressive lymphoma. The new staging system helps estimate survival better.

Efficacy and tolerability of nimotuzumab in combination with chemotherapy in recurrent and metastatic squamous cell carcinoma of head and neck at a cancer center in Northern India.

INTRODUCTION: Squamous cell carcinoma of head and neck (SCCHN) account for approximately 30-33% of all cancer and the median survival for recurrent and metastatic(R/M) SCCHN remains less than 1 year despite modern advances in therapy. Chemotherapy, usually single agent remains the backbone of therapy in these patients. EGFR antibodies are being used in (R/M) SCCHN. Nimotuzumab is one such agent that has anti-EGFR action similar to other agents without similar skin toxicity. METHODS: Prospective, interventional, non-randomized study done at Rajiv Gandhi Cancer Institute and Research Centre. A total 124 patients were enrolled and divided into Arm A (Chemotherapy + Nimotuzumab) and Arm B (Chemotherapy) in a ratio of 1:1 i.e., 62 in each arm. They were evaluated and treated as per protocol after a written informed consent. Statistical analysis was done using the SPSS software. Quantitative variables were compared using Unpaired t-test/Mann-Whitney Test. Qualitative variables were compared using Chi-Square test /Fisher's exact test. Kaplan-Meier analysis was used to assess the PFS, with log rank test for comparison between the groups. A p value of < 0.05 was considered statistically significant. RESULTS: The most frequent primary location of tumor was oral cavity (n=38, 69%) and (n=33, 56.9%) in both arms. The overall response rate in Arm A was 38.2% and 19% in Arm B (p= 0.023). The disease control rate in Arm A was 74.5% and 43.1% Arm B (p= 0.0007). The median PFS in Arm A was 5.2 months whereas it was 3.2 months in Arm B (p= 0.009). CONCLUSION: In this study, the combination of Nimotuzumab plus platinum/taxane based chemotherapy was active and well tolerated in Indian patients in R/M SCCHN. Addition of Nimotuzumab to chemotherapy had a response rate of 38.2% and median PFS of 5.2 months are strong arguments for clinically testing this combination.

Effect of antitubercular treatment on ovarian function in female genital tuberculosis with infertility.

AIM: To evaluate the effect of antitubercular therapy (ATT) on an ovarian function such as ovarian reserve, ovarian dimensions, and ovarian stromal blood flow. SETTINGS AND DESIGN: Prospective study design. MATERIALS AND METHODS: Fifty infertile women with female genital tuberculosis (FGTB) without tubo-ovarian masses diagnosed by positive acid-fast bacilli culture or epithelioid granuloma on endometrial aspirate or positive polymerase chain reaction with positive findings on laparoscopy or hysteroscopy were recruited. The ovarian function tests were performed on day 2/3 as follicle-stimulating hormone (FSH) levels and anti-Mullerian hormone (AMH) levels. Ovarian dimensions (length, width, and depth) were measured using a transvaginal ultrasound. Mean antral follicle count (AFC) and ovarian stromal blood flow (peak systolic velocity [PSV], pulsatility index (PI), and resistive index [RI]) were measured using a transvaginal ultrasound. All women were started on ATT for 6 months by directly observed treatment strategy. After completion of ATT, all the parameters were repeated. RESULTS: There was a significant increase in AMH (2.68 ± 0.97 ng/ml to 2.8 ± 1.03 ng/ml) pre- to post-ATT, nonsignificant increase in FSH (7.16 ± 2.34 mIU/ml to 7.26 ± 2.33 mIU/ml) post-ATT, significant increase in mean AFC (7.40 ± 2.12-8.14 ± 2.17), PSV in the right ovary (6.015-6.11 cm/s) and left ovary (6.05-6.08 cm/s), PI in the right ovary (0.935-0.951 cm/s) and left ovary (0.936-0.957 cm/s), and RI in the right ovary (0.62 ± 0.01-0.79 ± 0.02) and left ovary (0.65 ± 0.02-0.84 ± 0.01) with ATT. There was no significant change in mean ovarian dimensions (ovarian length, breadth, and width) and summed ovarian volume with ATT. On laparoscopy, tubercles were seen in 27 (54%) women. Caseous nodules and encysted ascites were seen in 8% cases each. CONCLUSION: ATT improves the ovarian function (AMH and AFC) and ovarian blood flow in women with FGTB.

RP-LC gradient elution method for simultaneous determination of thiocolchicoside, aceclofenac and related impurities in tablet formulation.

OBJECTIVE: The aim of the present study is to develop a simple and precise HPLC method for simultaneous determination of thiocolchicoside, aceclofenac and related impurities in a tablet formulation and validate as per ICH guidelines. The aim of study extends to perform forced degradation study to trace the degradation pathways of potential degradant impurities. MATERIALS AND METHODS: The separation was achieved on a 4.6 mm × 100 mm, 3 µm C18 column at 40°C with the mobile phase containing 0.1 M ammonium acetate buffer and methanol in a gradient mode at a flow rate of 1.0 mL min(-1). The UV detection was carried out at 257 nm. RESULTS: Acelofenac, thiocolchicoside and their related compounds were well separated from each other with good resolution and symmetry factor without interference of excipients. The method for assay was linear in the range of 10-200 µg mL(-1) for aceclofenac and 0.4 to 8 µg mL(-1) for thiocolchicoside. CONCLUSION: The method was validated according to ICH guidelines and the acceptance criteria for accuracy, precision, linearity, specificity, robustness, ruggedness and system suitability were met in all cases. The method was highly specific, as two related compounds of thiocolchicoside and nine related compounds of aceclofenac were well separated from each other. Stress study ensured the specificity of the method as the unknown degradation products formed during stress studies did not interfere with the determination of thiocolchicoside and aceclofenac, thus proving the stability indicating capacity of the method.

Sebaceous carcinoma: clinicopathologic features and diagnostic role of immunohistochemistry (including androgen receptor).

OBJECTIVE: To explicate the clinicopathologic features of periocular sebaceous carcinoma (SC) and emphasize the importance of immunohistochemical staining that includes androgen receptor (AR) in their diagnosis. DESIGN: Retrospective study. METHODS: Clinical and histopathologic features in 56 patients with periocular SC were analyzed. Immunohistochemical staining for pan-cytokeratin (CK), epithelial membrane antigen (EMA), Ber-EP4, adipophilin (ADP), and AR was performed on all cases. Immunostaining in SC was compared with that of squamous cell carcinoma (SCC; n = 25) and basal cell carcinoma (BCC; n = 18) for all antibodies. RESULTS: SGC was more frequent in females, most commonly presenting as a discrete and nodular mass. Four patients had regional lymph node metastases, whereas in 2, the tumour metastasized to the liver. Eight patients had a locoregional recurrence between the 3rd and 45th months of follow-up. Fifty patients had a moderately differentiated tumour. In 3 patients, the resected margins displayed intraepithelial tumour spread, and 2 patients died of the disease. In general, the staining pattern in SGC was CK(+), EMA(+), BerEP4(-), ADP(+), and AR(+). SCCs were CK(+), EMA(+), Ber-EP4(-), ADP(-/+), and AR(-), whereas BCC were CK(+), EMA(-), Ber-EP4(+), ADP(-), and AR(-/+). p53 expression and Ki-67 index were higher in SC than SCC or BCC. CONCLUSIONS: Immunostaining using a panel of antibodies comprising BerEP4, ADP, EMA, and AR is useful in diagnosing sebaceous carcinoma and differentiating it from SCC and BCC, which are common to the periocular location and sometimes are morphologically identical to SC.

Periocular sebaceous gland carcinoma: do androgen receptor (NR3C4) and nuclear survivin (BIRC5) have a prognostic significance?

PURPOSE: The study aimed at evaluating the expression of androgen receptor (AR) and nuclear survivin (NS) in periocular sebaceous gland carcinoma (SGC) and to determine whether this expression is associated with histopathological features, markers of apoptosis and proliferation and with clinical outcomes. METHODS: This was a retrospective, comparative case series which included 56 patients with a biopsy-proven periocular SGC. Immunohistochemical staining for AR, survivin, p53 and Ki-67 was analysed in all cases. RESULTS: All patients expressed AR, p53 and Ki-67 in the nucleus of tumour cells. Twenty-four patients (42.8%) had a high AR score, and 32 patients (57.2%) had a low AR score. Twenty-four (42.8%) patients expressed survivin in the nucleus of tumour cells. Nine (37.5%) had a high NS score, and 15 (62.5%) had a low NS score. Patients with a high AR score had a greater recurrence (p < 0.005), higher expression of Ki-67 (p < 0.0001) and a lower p53 expression (p < 0.005). Nuclear expression of survivin correlated with a high Ki-67 labelling index (0.0001) and low p53 expression (<0.005). Neither nuclear expression of survivin nor the NS score correlated with any clinicopathological features. CONCLUSION: Expression of AR significantly impacts prognosis and is thus promising prognostic marker in periocular SGC.

Primary intraocular malignant extrarenal rhabdoid tumor: a clinicopathological correlation.

Malignant extrarenal rhabdoid tumor is a rare and highly aggressive tumor of childhood. Intraocular involvement by malignant extrarenal rhabdoid tumor has only been described once as a metastasis. No report exists in published literature describing a primary intraocular malignant extrarenal rhabdoid tumor. The authors report the first such case along with its clinico-radiological features and histopathologic and electron microscopic characteristics.

Primary intraocular malignant extrarenal rhabdoid tumor: a clinicopathological correlation.

Malignant extrarenal rhabdoid tumor is a rare and highly aggressive tumor of childhood. Intraocular involvement by malignant extrarenal rhabdoid tumor has only been described once as a metastasis. No report exists in published literature describing a primary intraocular malignant extrarenal rhabdoid tumor. The authors report the first such case along with its clinico-radiological features and histopathologic and electron microscopic characteristics.

RP-HPLC method for simultaneous estimation of bisoprolol fumarate and hydrochlorothiazide in tablet formulation.

A simple, precise and stability-indicating HPLC method was developed and validated for the simultaneous determination of bisoprolol fumarate and hydrochlorothiazide in pharmaceutical dosage form. The method involves the use of easily available inexpensive laboratory reagents. The separation was achieved on an Inertsil ODS 3V (25cmx4.6mm) 5microm column with isocratic flow. The mobile phase at a flow rate of 1.0mLmin(-1), consisted of 0.1M potassium dihydrogen phosphate buffer and acetonitrile (70:30, v/v). The UV detection was carried out at 228nm. A linear response was observed over the concentration range 2.5-50microgmL(-1) of bisoprolol fumarate and the concentration range 6.25-125microgmL(-1) of hydrochlorothiazide. Limit of detection and limit of quantitation for bisoprolol fumarate were 0.01 and 0.03microgmL(-1), respectively and for hydrochlorothiazide were 0.01 and 0.05microgmL(-1), respectively. The method was successfully validated in accordance to ICH guidelines acceptance criteria for specificity, linearity, accuracy, precision, robustness, ruggedness and system suitability. Individual drugs (bisoprolol fumarate and hydrochlorothiazide), their combinations and the tablets were exposed to thermal, photolytic, hydrolytic and oxidative stress conditions. The resultant stressed samples were analyzed by the proposed method. The method gave high resolution among the degradation products and the analytes. The peak purity of analyte peaks in the stressed samples was confirmed by photodiode array detector. The method was used for accelerated stability study on marketed and in-house formulations. The analysis concluded that the method was selective for simultaneous estimation of bisoprolol fumarate and hydrochlorothiazide and was stability-indicating.

Reimbursement trends for outpatient interventional radiology procedures: comparison of hospital and freestanding physician office sites of service.

PURPOSE: The aim of this study was to compare trends in reimbursement rates between hospital outpatient departments and freestanding physician offices for commonly performed interventional radiology procedures from 2006 through 2010. METHODS: Using final rules data from the 2006 and 2008 Hospital Outpatient Prospective Payment System for Medicare and Medicare Physician Fee Schedule, reimbursement rates were calculated for a sample of procedures commonly performed by interventional radiologists in the outpatient setting. Hospital and freestanding reimbursement rates for 2006, 2008, and 2010 (projected) were adjusted for inflation to 2008 dollars and weighted by relative procedure frequency using Medicare Part B claims data. Reimbursements for the entire sample of procedures were compared year to year, by site of service, and by payment system. Individual procedure reimbursements were also trended. RESULTS: In 2006, reimbursements for the entire procedure sample were 6% less in hospital outpatient departments than in freestanding offices. In 2008 and 2010, they are projected to be 3% and 23% greater, respectively, in hospital outpatient departments than in freestanding offices. Over the 4-year interval, reimbursements are projected to fall by 36% in freestanding offices and by 16% in hospital outpatient departments. Reimbursements to hospitals for facility costs are projected to decrease by 14%. Reimbursements to physicians for work done in hospital outpatient departments are projected to decrease by 23%. CONCLUSIONS: Substantial reductions in calculated outpatient interventional radiology practice expenses being phased in between 2006 and 2010 under the Medicare Physician Fee Schedule seem to be dramatically reducing reimbursements for interventional procedures performed on outpatients, especially in freestanding offices. The impact of these practice expense reductions on interventional radiology seems to far outweigh that of the Deficit Reduction Act and other recent Medicare reimbursement changes.

Verapamil versus saline in electromotive drug administration for Peyronie's disease: a double-blind, placebo controlled trial.

PURPOSE: While surgery remains the gold standard of therapy to correct the acquired curvature of Peyronie's disease, the search for a less invasive therapy continues. Transdermal drug delivery was proposed to be superior to oral or injection therapy because it bypasses hepatic metabolism and minimizes the pain of injection. After electromotive drug administration with verapamil tunica albuginea specimens were demonstrated to contain detectable levels of the drug. Due to varying success with verapamil as injectable therapy for Peyronie's disease we performed a double-blind, placebo controlled trial to determine the effectiveness of verapamil delivered through electromotive drug administration. MATERIALS AND METHODS: A total of 42 men with Peyronie's disease volunteered to participate in this study, which was approved by our institutional review board. A genitourinary examination was performed on all patients, including plaque location, stretched penile length, objective measurement of curvature after papaverine injection and duplex ultrasound. Each subject was randomized to receive 10 mg verapamil in 4 cc saline or 4 cc saline via electromotive drug administration. A Mini-Physionizer (Physion, Mirandola, Italy) device was used at a power of 2.4 mA for 20 minutes. Treatments were performed 2 times weekly for 3 months. After 3 months each patient was reevaluated with physical examination and duplex ultrasound by a technician blinded to the treatment received. A modified erectile dysfunction index of treatment satisfaction questionnaire was also completed by each patient. RESULTS: A total of 23 patients were randomized to the verapamil treatment group (group 1) and 19 were randomized to the saline group (group 2). There were no significant differences between patient groups with respect to patient age, disease duration or pretreatment curvature. In group 1, 15 patients (65%) had measured improvement (mean 9.1 degrees, range 5 to 30), 5 (22%) had no change and in 3 (13%) the condition worsened. In group 2, 11 patients (58%) had measured improvement (mean 7.6 degrees, range 5 to 30), 7 (37%) showed no change and in 1 (5%) the condition worsened. To better evaluate effectiveness the total number of patients experiencing significant improvement (20 degrees or greater) was calculated and compared. Seven patients (30%) in group 1 and 4 (21%) in group 2 achieved this criterion. Although a greater percent of patients treated with verapamil had improved curvature, the results were not statistically significant. CONCLUSIONS: Although a greater percent of patients treated with verapamil in our electromotive drug administration protocol had a measured decrease in curvature, the results were not statistically significant. Further research is necessary to determine whether electric current may have a role in the treatment of Peyronie's disease as well as if verapamil delivered via electromotive drug administration may have a role as effective treatment. Electromotive drug administration is a treatment option in the patient whose major complaint is pain or in the patient with mild curvature who does not wish to undergo intralesional therapy or surgical correction.