Prophylactic Mechanical Circulatory Support Use in Elective Percutaneous Coronary Intervention for Patients With Stable Coronary Artery Disease.

BACKGROUND: Mechanical circulatory support (MCS) devices can be used in high-risk percutaneous coronary intervention (PCI). Our objective was to describe trends and outcomes of prophylactic MCS use in elective PCI for patients with stable coronary artery disease in the American College of Cardiology National Cardiovascular Data Registry's CathPCI registry. METHODS: Among 2 108 715 consecutive patients with stable coronary artery disease undergoing elective PCI in the CathPCI registry between 2009 and 2018, we examined patterns of prophylactic use of MCS. Propensity score models with inverse probability of treatment weighting compared effectiveness (in-hospital death, cardiogenic shock, or new heart failure) and safety (stroke, tamponade, major bleeding, or vascular complication requiring treatment) between patients treated with intra-aortic balloon pump versus other MCS (Impella or extracorporeal membrane oxygenation). RESULTS: Overall, 6905 (0.3%) patients underwent elective PCI with prophylactic MCS. MCS use trended up from 0.2% of elective PCIs in 2009 to 0.6% in 2018 (P<0.0001), driven by other MCS (P<0.0001), whereas intra-aortic balloon pump use remained low and constant (P=0.12). In-hospital major adverse cardiac events and cardiovascular complications occurred in 7.1% and 18.8% of elective PCI patients with prophylactic MCS use and 0.5% and 2.3% of patients without prophylactic MCS use. Intra-aortic balloon pump use was associated with a higher risk of major adverse cardiac events (9.6% versus 6.0%, adjusted odds ratio, 1.59 [95% CI, 1.32-1.91]) but lower risk of complications (18.2% versus 19.1%, adjusted odds ratio, 0.88 [95% CI, 0.77-0.99]) than use of other MCS. CONCLUSIONS: The use of prophylactic MCS has increased over time for elective PCI in patients with stable coronary artery disease. Intra-aortic balloon pump was associated with higher major adverse cardiac events but lower risk of procedural complications compared with other MCS.

Redefining the importance of polylactide-co-glycolide acid (PLGA) in drug delivery.

The limitations of non-biodegradable polymers have paved the way for biodegradable polymers in the pharmaceutical and biomedical sciences over the years. Poly (lactic-co-glycolic acid) (PLGA), also known as "Smart polymer", is one of the most successfully developed biodegradable polymers due to its favorable properties, such as biodegradability, biocompatibility, controllable drug release profile, and ability to alter surface with targeting agents for diagnosis and treatment. The release behavior of drugs from PLGA delivery devices is influenced by the physicochemical properties of PLGA. In this review, the current state of the art of PLGA, its synthesis, physicochemical properties, and degradation are discussed to enunciate the boundaries of future research in terms of its applicability with the optimized design in today's modern age. The fundamental objective of this review is to highlight the significance of PLGA as a polymer in the field of cancer, cardiovascular diseases, neurological disorders, dentistry, orthopedics, vaccine therapy, theranostics and lastly emerging epidemic diseases like COVID-19. Furthermore, the coverage of recent PLGA-based drug delivery systems including nanosystems, microsystems, scaffolds, hydrogels, etc. has been summarized. Overall, this review aims to disseminate the PLGA-driven revolution of the drug delivery arena in the pharmaceutical and biomedical industry and bridge the lacunae between material research, preclinical experimentation, and clinical reality.

Development, validation, and application of an RP-HPLC method for concurrent quantification of Minoxidil and Finasteride in a topical solution for hair regrowth.

A topical solution comprising of Minoxidil (MXL) and Finasteride (FNS) for alopecia is formulated in the present work, which essentially contains a lipid-Lauroglycol FCC as a penetration enhancer. The objective of the proposed work was to develop a rapid, simple, and robust reverse phase high performance liquid chromatographic (RP-HPLC) method to determine MXL and FNS in the said formulation. Herein, the chromatographic conditions were optimized based on the theoretical principles of separation and physicochemical properties such as pKa and log P of both the Active Pharmaceutical Ingredients (APIs). The separation was accomplished on an Inertsil® ODS-3 C18 column (150mm×4.6mm; 5µm of particle size) at 25°C by using a mobile phase composed of 70:30 v/v ratio of Methanol and Milli-Q water along with 0.5% Triethylamine at pH 6.4 adjusted with Ortho Phosphoric Acid. Drug peaks showed a good resolution at 210nm. The retention times for MXL and FNS were found to be 2.40min and 6.39min, respectively. The developed method was found to be linear (R2≥0.998) in a concentration range of 5-100µg/mL for both the drugs. The method was validated according to the ICH guidelines Q2 (R1). The ability of the method to differentiate between the types formulations was demonstrated by the in vitro diffusion data performed using a highly sophisticated Strat-M® membrane. The cumulative amount of drug released (MXL and FNS) at the end of 24hours was maximum for the topical formulation containing lipids prepared using isopropyl alcohol and propylene glycol as the base.

Assessing the effects of manual dexterity and playing computer games on catheter-wire manipulation for inexperienced operators.

AIM: To investigate the effect of playing computer games and manual dexterity on catheter-wire manipulation in a mechanical aortic model. MATERIAL AND METHODS: Medical student volunteers filled in a preprocedure questionnaire assessing their exposure to computer games. Their manual dexterity was measured using a smartphone game. They were then shown a video clip demonstrating renal artery cannulation and were asked to reproduce this. All attempts were timed. Two-tailed Student's t-test was used to compare continuous data, while Fisher's exact test was used for categorical data. RESULTS: Fifty students aged 18-22 years took part in the study. Forty-six completed the task at an average of 168 seconds (range 103-301 seconds). There was no significant difference in the dexterity score or time to cannulate the renal artery between male and female students. Students who played computer games for >10 hours per week had better dexterity scores than those who did not play computer games: 9.1 versus 10.2 seconds (p=0.0237). Four of 19 students who did not play computer games failed to complete the task, while all of those who played computer games regularly completed the task (p=0.0168). CONCLUSION: Playing computer games is associated with better manual dexterity and ability to complete a basic interventional radiology task for novices.

Advanced Ovarian Cancer: Primary or Interval Debulking? Five Categories of Patients in View of the Results of Randomized Trials and Tumor Biology: Primary Debulking Surgery and Interval Debulking Surgery for Advanced Ovarian Cancer.

BACKGROUND: Standard treatment of stage III and IV advanced ovarian cancer (AOC) consists of primary debulking surgery (PDS) followed by chemotherapy. Since the publication of the European Organisation for Research and Treatment of Cancer/National Cancer Institute of Canada trial, clinical practice has changed and many AOC patients are now treated with neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS). The best option remains unclear. Ovarian cancer is a heterogenic disease. Should we use the diversity in biology of the tumor and patterns of tumor localization to better stratify patients between both approaches? METHODS: This analysis was based on results of five phase III randomized controlled trials on PDS and IDS in AOC patients, three Cochrane reviews, and four meta-analyses. RESULTS: There is still no evidence that NACT-IDS is superior to PDS. Clinical status, tumor biology, and chemosensitivity should be taken into account to individualize surgical approach. Nonserous (type 1) tumors with favorable prognosis are less chemosensitive, and omitting optimal PDS will lead to less favorable outcome. For patients with advanced serous ovarian cancer (type 2) associated with severe comorbidity or low performance status, NACT-IDS is the preferred option. CONCLUSION: We propose stratifying AOC patients into five categories according to patterns of tumor spread (reflecting the biologic behavior), response to chemotherapy, and prognosis to make a more rational decision between PDS and NACT-IDS. IMPLICATIONS FOR PRACTICE: Trial results regarding effect and timing of debulking surgery on survival of patients with advanced ovarian cancer have been inconsistent and hence difficult to interpret. This review examines all randomized trials on primary and interval debulking surgery in advanced ovarian cancer, including the results of the newly published CHORUS (chemotherapy or upfront surgery for newly diagnosed advanced ovarian cancer) trial. On the basis of findings presented in this review and in view of recent molecular data on the heterogeneity of ovarian tumors, we propose prognostic categorization for patients with advanced ovarian cancer to better distinguish those who would optimally benefit from primary debulking from those who would better benefit from interval debulking following neoadjuvant chemotherapy.

Management of Acute Pulmonary Embolism: Consensus Statement for Indian Patients.

Pulmonary embolism (PE) is an important cause of morbidity and mortality among hospitalized patients. Although the exact epidemiology of PE is not known in India, Some of the studies show that more frequently it is missed and not managed appropriately leading to significant cardiovascular morbidity and mortality. Justification and purpose: Indian guidelines for the diagnosis and treatment of acute PE are not yet formulated. The objective of this consensus statement is to propose a diagnostic and management approach for acute PE in India. PROCESS: A working group of 15 experts in the management of acute PE (cardiologists, pulmonologist, haematologist, emergency specialist and intensivists). This consensus statement makes recommendations for diagnosis and management for PE based on literature review, including Indian data.

Quiescent-inflow single-shot magnetic resonance angiography using a highly undersampled radial k-space trajectory.

PURPOSE: We hypothesized that high undersampling factors could be used in conjunction with radial quiescent-inflow single-shot magnetic resonance angiography (MRA) to accelerate the data acquisition and enable multislice acquisitions. METHODS: Seven subjects were imaged on a 1.5 T MRI system. For multislice quiescent-inflow single-shot MRA, the venous saturation radiofrequency pulse, in-plane saturation radiofrequency pulse, and quiescent interval were applied only once before the first slice. RESULTS: The mean (standard deviation) measurements for the intra-arterial signal-to-noise ratio were as follows: Cartesian 1 slice-29.3 (5.5); radial 1 slice, 92 views-22.3 (3.6); radial 1 slice, 46 views-18.5 (2.0); radial 2 slices, 46 views-18.3 (3.2); and radial 3 slices, 32 views-21.7 (3.9), normalized for pixel size to 15.8. Horizontal striping was present with multislice radial quiescent-inflow single-shot MRA (especially with the three-slice acquisition) due to variable T1 relaxation between the concurrently acquired slices, but the image quality remained diagnostic. Vascular pathology in patients with peripheral arterial disease was well shown by all techniques. CONCLUSION: Very high undersampling factors in excess of 18 have been demonstrated for nonenhanced MRA using a radial quiescent-inflow single-shot technique, enabling the acquisition of two to three slices per cardiac cycle. Scan time for a complete peripheral MRA could be shortened to 2 min or less.

Sentinel node procedures in gynecologic cancers: an overview.

The aim of this study was to assess the value of sentinel lymph node procedures in gynecologic cancers. A systematic literature overview, using the PubMed database, was performed. In early stage vulvar, endometrial and cervical cancer, lymph node status is the most important prognostic factor. Lymphadenectomy, performed for adequate staging, is associated with high morbidity rates. Sentinel node procedures hold the promise of adequate staging with less treatment-related morbidity. Sentinel lymph node procedures in patients with early-stage vulvar cancer are associated with low recurrence rates, excellent survival, lower morbidity and shorter hospital stay compared to classical inguinal dissection. Therefore, these procedures should be the standard of care in early-stage unilateral vulvar cancer. Reports on sentinel lymph node procedures in endometrial and cervical cancer are ambiguous. The procedures in these cancers are reported in small studies only. Detection rates vary depending on the used injection sites and the used tracers. Bilateral detection rates are low and are not mentioned by default. Large controlled multi-institutional studies are necessary to evaluate the validity and the prognostic significance of the sentinel lymph node procedures in endometrial and cervical cancer.

BD-ProExC as adjunct molecular marker for improved detection of CIN2+ after HPV primary screening.

BACKGROUND AND METHODS: We investigated the efficacy of 8 cervical cancer screening strategies relative to cytology with emphasis on immunocytochemical detection of high-risk human papillomavirus (hrHPV)-induced cell transformation (BD-ProExC) as a tool of triage following primary cytology or hrHPV testing. 3,126 women were tested with BD-SurePath liquid-based cytology, hrHPV PCR genotyping and BD-ProExC immunostaining, and colposcopy verification to calculate sensitivity and positive predictive value (PPV) in detecting cervical intraepithelial neoplasia (CIN2(+)). RESULTS: Compared to cytology screening, double testing with cytology and hrHPV resulted in the same sensitivity with a significant increase in the PPV (relative PPV: 1.83). However, twice as many tests were needed. Cytology with atypical squamous cells of undetermined significance (ASC-US) triage and hrHPV testing showed comparative results to double testing requiring only a small increase in number of tests. Screening for hrHPV subtypes 16/18, and ASC-US triage with hrHPV16/18 resulted in significant reductions in sensitivity (ratio: 0.74 and 0.96, respectively). Primary hrHPV/BD-ProExC screening was significantly more sensitive (ratio: 1.63/1.33), but had a significantly lower PPV (ratio: 0.64/0.88). ASC-US triage by BD-ProExC increased the PPV (ratio: 1.90) but decreased the sensitivity (ratio: 0.96). Primary hrHPV screening followed by BD-ProExC triage, led to significant increases in sensitivity (ratio: 1.30) and PPV (ratio: 2.89), and resulted in 55% fewer referrals for colposcopy. CONCLUSIONS: From the investigated screening strategies, primary hrHPV DNA-based screening followed by BD-ProExC triage was determined to be the best screening strategy. IMPACT: Immunocytological triage could be used to perfect hrHPV primary screening.

Chronic suppurative otitis media in Nepal: ethnicity does not determine whether disease is associated with cholesteatoma or not.

OBJECTIVES: To determine the frequency of cholesteatoma in a population of patients with chronic suppurative otitis media, and to determine whether this frequency is affected by ethnicity. PATIENTS: The study included 6005 patients with chronic suppurative otitis media seen during the course of 30 charitable surgical 'ear camps' in Nepal. MAIN OUTCOME MEASURES: Proportion of patients with each subtype of disease, and their ethnicity. A secondary outcome measure was concordance of surname with Nepalese ethnic affiliation. RESULTS: A total of 762 patients were grouped as being of Tibeto-Mongolian origin, and 4875 as Indo-Caucasian. The rate of chronic suppurative otitis media with cholesteatoma, expressed as a proportion of the rate of all chronic suppurative otitis media subtypes, was 17.8 per cent in Tibeto-Mongolian patients and 18.6 per cent in Indo-Caucasian patients (p > 0.05). The effect of other risk factors (i.e. age, gender and geographical district) on disease distribution was also non-significant. Analysis of secondary outcome measures indicated that patients' surnames were a reliable predictor of ethnicity in this Nepalese population. CONCLUSION: There is almost complete concordance in proportions of patients with significant genetic, cultural, and even geographical heterogeneity, suggesting that, in Nepal, the aetiology of cholesteatoma owes little to these factors.

Wide excision and ulno-carpal arthrodesis for primary aggressive and recurrent giant cell tumours.

Twenty-five patients underwent wide resection of the distal radial giant cell tumours (GCTs) followed by ulno-carpal arthrodesis. There were 15 male and ten female patients, with an average age of 21.5 years. Tumours included ten primary aggressive and 15 recurrent GCTs. Mean follow up was 2.4 years. Pain, swelling and reduced range of movement (ROM) were noted. Average time to fusion was 7.6 months. Five patients had persistent pain in the proximal forearm. Grip strength was 65% compared to the uninvolved side. Two patients had superficial wound infection, two underwent additional bone grafting and three implant removals due to hardware prominence were carried out. There was no evidence of carpal instability or arthritis on clinical or radiological examination at the time of final follow up. Fusion of the carpus to the ulna is a simple method of producing a painless stable wrist, though at the expense of mobility. The procedure allows wide resection with a lower rate of recurrence. Pain in the proximal forearm seems to persist for 3 to 4 months only to improve at subsequent follow up. The procedure provides a valid option for the management of primary aggressive and recurrent GCTs of distal radius.

A rare case of progressive bilateral congenital abduction contracture with shoulder dislocations treated with proximal deltoid release.

The contracture of the deltoid muscle is an uncommon disorder. Amongst the various causes reported, post intramuscular injection and trauma leading to the fibrosis of the muscle are common. However, congenital cases are extremely rare. We report a case of congenital progressive bilateral abduction contracture left untreated for a long time leading to anteroinferior subluxation. A proximal release was performed with satisfactory outcome on both sides.

Use of the levonorgestrel-releasing intrauterine system in breast cancer patients.

OBJECTIVE: To study the recurrence of breast cancer among patients who were using the levonorgestrel-releasing intrauterine system (LNG IUS). DESIGN: A retrospective, controlled cohort analysis. SETTING: Six Belgian hospitals. PATIENT(S): We identified 79 breast cancer patients who used the LNG IUS, and we selected a control group of 120 patients with no history of LNG IUS use and who were closely matched for age at diagnosis, tumor stage, tumor grade, and treatment modalities. Two subgroups were identified: [1] breast cancer patients who continued using the LNG IUS after diagnosis and [2] breast cancer patients who began using an LNG IUS after treatment for breast cancer. INTERVENTION(S): Patient's data were collected and survival analysis was performed. MAIN OUTCOME MEASURE(S): Breast cancer recurrence rate. RESULT(S): There was a recurrence rate of 21.5% (17/79) among LNG IUS users and of 16.6% (20/120) among the control group (adjusted hazard ratio, 1.86; 95% confidence interval, 0.86-4.00; no statistically significant difference). Subgroup analysis showed that women using the LNG IUS (n = 38) at the time of breast cancer diagnosis (and who continued its use) had a statistically significantly increased risk of recurrence (adjusted hazard ratio, 3.39; 95% confidence interval, 1.01-11.35) compared with patients in the control group. There was 47.4% (18/38) nodal involvement in this subgroup, and all patients who recurred had metastatic disease. CONCLUSION(S): Overall, we did not find an increased risk of breast cancer recurrence associated with use of the LNG-IUS. However, in a subgroup analysis of women who developed breast cancer while using an LNG IUS and who continued to use the LNG IUS, we found a higher risk of recurrence of borderline statistical significance. Additional research is needed to confirm or refute these findings.

Self-administration of vaginal misoprostol after mifepristone for termination of pregnancy: patient acceptability.

This was a questionnaire survey involving women who self-administered vaginal misoprostol in the hospital setting following oral mifepristone for medical termination of pregnancy. The sample number was 89 with a median gestational age of 9 weeks; median dose of misoprostol used was 1600 mug and median induction abortion interval was 5.3 h. The success rate was 100% with the majority finding it easy to self-administer vaginal misoprostol and two-thirds did not mind doing this. Only one-third experienced adverse effects of the medication and 83% were satisfied with the procedure. Only one-third was willing to try it at home in future if necessary. Self-administration of vaginal misoprostol for termination of pregnancy in the hospital is safe and effective. Although women were comfortable in self administering the pessaries in the hospital, they do not appear to be keen to do it at home without any supervision. However, as this is the first study in the UK involving women expressing their views regarding this issue, added research in this area is required.

Self-administration of misoprostol for termination of pregnancy: safety and efficacy.

We conducted a retrospective study to determine the efficacy and safety of self-administration of vaginal misoprostol (following oral mifeprestone) for medical termination of pregnancy. This study revealed that self-administration was accepted by the majority of the patients (90%) and the success rate (98.4%) and duration of hospital stay was not altered significantly compared to our previous year's data, where women were administered vaginal misoprostol by the staff. Based on this study's results, we are of the opinion that this regimen not only demedicalises the problem but also decreases the workload for the medical staff.

A pilot study of the beneficial effects of amantadine in the treatment of painful diabetic peripheral neuropathy.

BACKGROUND: Current symptomatic treatments for painful peripheral neuropathy in diabetes have variable efficacy in individual patients. Amongst other chemical transmitters involved in pain reception, the N-methyl-D-aspartate (NMDA) subtype of excitatory amino acid receptor is involved in nociception. Amantadine was recently shown to act as a non-competitive antagonist of NMDA and may be effective in the treatment of neuropathic pain in patients with cancer. We have looked at the benefit of amantadine infusion in diabetic patients with painful peripheral neuropathy. METHODS: Seventeen patients with diabetes (nine men) completed this double-blind randomized crossover placebo-controlled trial of intravenous amantadine. The average age was 58.4 (sd 11) years, with duration of diabetes of 21.1 (8.7) years and duration of painful peripheral neuropathy symptoms of 29.1 (24) months. All analgesics except paracetamol were stopped for 4 weeks prior to the study. Infusions were carried out on a weekly basis with amantadine being administered intravenously as a single 200-mg infusion. The Neuropathy Symptom Score (NSS), together with visual analogue scales, were used to assess current pain intensity (VAS-P) pre-therapy and 1 week later VAS-P was repeated together with a visual analogue scale used to assess relief in pain (VAS-R) and the Physicians Global Evaluation (PGE) score used to assess response to therapy. RESULTS: Pre-therapy, the NSS was 6.8 (6.3-7.4) at baseline, remaining unchanged at 6.6 (5.8-7.4) after placebo (P = 0.33), but fell to 4.6 (3.4-5.8) after amantadine (P = 0.003 vs. baseline and P = 0.02 vs. placebo). The baseline perception of pain was scored as 7.8 cm (7.3-8.3), with no difference following placebo, at 8.2 cm (7.7-8.6) (P = 0.34), but following amantadine it fell to 6.2 cm (4.9-7.8) (P = 0.01 compared with pre-therapy, P = 0.003 compared with placebo). The perception of relief from pain following placebo was only 0.2 (-0.2 to +0.6) but following amantadine was 10-fold better at 1.9 (0.8-3.1) (P = 0.016). The PGE assessment of pain relief was -0.3 (-0.5 to 0) for placebo and following amantadine was 0.8 (0.1-1.5) (P = 0.006). CONCLUSIONS: Our study has shown that intravenous amantadine is beneficial in reducing the pain of painful peripheral neuropathy, with an effect sustained for at least 1 week after an infusion.

A stability indicating LC method for felodipine.

A stability indicating reversed-phase liquid chromatographic (RP-LC) method was developed for the assay of felodipine as a bulk drug and in pharmaceuticals. The chromatography was performed on a C18 column. Eluents were monitored by UV detection at 238 nm using the mobile phase methanol-potassium dihydrogen orthophosphate (pH 3.5; 0.01 M) (75:25, v/v). The method was statistically validated for linearity, accuracy, precision and specificity. The linearity of felodipine peak area responses was demonstrated within the concentration range of 1-7 microg/ml. The limits of detection and quantitation were 150 and 500 ng/ml, respectively. The method was demonstrated to be precise, accurate and specific with no interference from the tablet excipients and separation of the drug peak from the peaks of the degradation products (oxidative degradation, photodegradation, acid and base degradation). The results indicated that the proposed method could be used in a stability assay.