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Abstract Background To compare the rate of fractional change for multiple corneal tomographic factors in progressive keratoconus (KC). Methods In this retrospective case series, 40 eyes (40 patients) with progressive KC (increase in central keratometry of 1.00 D or maximum keratometry of 1.50 D on two visits at least six months apart) were included. Cases with previous history of ocular surgery, poor scans, corneal scars, severe dry eyes, post-excimer ectasia, pellucid marginal degeneration were excluded. Medical records, corneal tomography and anterior corneal wavefront (8 mm) (Scheimpflug tomography, Pentacam, Oculus, Germany) were analyzed. Rate of fractional change (Rx = (x1 − x0)/(|x0|tm)); where, x1 = value at follow-up, x0 = value at initial visit and tm = time in months, was measured. Results The mean age of the patients was 30.0 ± 8.4 years. The mean follow-up duration was 8.9 ± 4.2 months. Coma (0.076 ± 1.4) had the largest rate of fractional change (P = 1.7 × 10−14, Kruskal–Wallis test). The rate of fractional change was higher for aberrometric parameters (anterior corneal higher-order aberrations root mean square and anterior coma) compared to pachymetric and keratometric parameters (P values ranging from 1.4 × 10−4 to 7.4 × 10−10, Mann–Whitney test, effect size ranging from 0.4–0.7). The rate of fractional change was comparable between pachymetric and keratometric factors (P > 0.05 for all comparisons, Mann–Whitney test). Conclusions Anterior corneal wavefront, especially anterior coma, were noted to have higher rate of fractional change compared to single point keratometric and pachymetric indices in progressive KC. This information can be used for decision-making when monitoring patients with KC.

Transition-metal-catalyzed C–H arylations are an effective tool for the construction of biaryl motifs in an efficient and selective manner. Here the authors provide an overview of the state-of-the-art of the field and perspectives on emerging directions toward increased sustainability.

Background The incidence of a bifid electrophoretic pattern in the albumin region on serum protein electrophoresis is an infrequent phenomenon. The availability of literature from India is scarce and is limited to case reports. Objective The aim of the study is to analyze the frequency of bisalbuminemia in an Indian referral facility. The study delved into their clinical associations. Material and Methods The retrospective case records of the patient from the departmental database were scrutinized. The study subjects were for an 8-year study period. Results There were about 39,900 serum electrophoresis performed in an 8-year study period. A total of 40 cases of bisalbuminemia were detected. The incidence in our cohort was 0.01%. Conclusion Bisalbuminemia, an overtly benign condition, is infrequent in Indian population although not rare. It is associated with several clinical disorders; however, the association seems to be plausibly coincidental.

PURPOSE Chronic lymphocytic leukemia (CLL) is uncommon in India. There are limited studies on CLL from the Indian subcontinent. METHODS This was a prospective study (2011-2017) of consecutively diagnosed patients with CLL at a single center. The diagnosis, prognosis, treatment indication, response criteria, and adverse events were recorded as per International Workshop on Chronic Lymphocytic Leukemia guidelines. Biosimilar rituximab dosing (375 mg/m2) was fixed for all cycles. Time to next treatment (TTNT) was defined as the time from front-line treatment initiation to next treatment or death from any cause. Overall survival (OS) was defined as the time from treatment initiation until death from any cause. RESULTS A total of 409 patients with CLL were enrolled over the study period. The median follow-up was 32 months (range, 2-135 months). The median age was 61 years, and 31.8% of patients with CLL were ≤ 55 years of age; 43.3% of patients had a cumulative illness rating scale score ≥ 3. Prognostic fluorescence in situ hybridization data were available in 53.3% of patients. Chlorambucil (94/180; 52.2%) and bendamustine + rituximab (BR; 57/180; 31.6%) were the most common regimens used up front. The overall response rates after front-line therapy were 74.4% and 91.2%, respectively. The TTNT was 33 months and not reached, respectively (P = .001). Grade 3/4 neutropenia and infections were seen in 52.6% and 38.5% of patients receiving BR. The median OS was not reached in both regimens (P = .25). CONCLUSION Indian patients with CLL are younger in chronological age but have higher morbidity burden. Treatment outcomes with biosimilar fixed-dose BR are comparable to those reported in the literature. Chlorambucil is still a valid option, given the economic burden of the disease and treatment.

Background Prognosis of gallbladder cancer (GBC) has not changed in the past 20 years. Comprehensive genomic profiling (CGP) carries potential to determine the actionability for multiple targets, including ERBB2, ERBB3, MET, ROSI, FGFR, and PIK3. This study evaluates the role of CGP and targeted therapies. Methods This is a multicenter, prospective, single-arm study. All consecutive patients of unresectable and/or metastatic GBC of age ≥18 years were enrolled. Hybrid capture-based CGP was performed by Foundation Medicine CDx. All patients received first-line chemotherapy with gemcitabine–cisplatin regimen. Patients with ERBB2/3 amplification received trastuzumab with capecitabine or nab-paclitaxel, and patients with MET amplification were treated with crizotinib. For ERBB2/3 mutations, lapatinib plus capecitabine regimen was used. Results Fifty patients were studied with a median age of 56 years (range 26–83) and a male-to-female ratio of 1:1.6. ERBB2 and ERBB3 amplification was seen in 9 (18%) and 2 (4%) patients, respectively. Four patients with ERBB2 amplification received trastuzumab and/or lapatinib, showed partial response, and maintained response beyond 12 weeks. One patient had mixed response, whereas two patients progressed on trastuzumab and lapatinib. Three patients with ERBB3 mutations showed response to lapatinib–capecitabine. One patient with MET amplification responded to crizotinib for 4 weeks. PIK3 mutations were present in 14% of cases and were independent of ERBB aberrations. Conclusion GBC is enriched in 28% of patients with ERBB2 and ERBB3 amplifications and/or mutations. Responses are seen with lapatinib in concurrent ERBB2 mutation and amplification. ERBB3 mutation showed response to lapatinib. MET and PIK3 are new findings in GBC, which may be targeted.

Background: Chronic kidney disease (CKD) predisposes to accelerated atherosclerosis that is measured by carotid artery intima media thickness (CIMT) and brachial artery flow-mediated dilation (FMD). The aim of this study was to assess the noninvasive risk markers of subclinical atherosclerosis and endothelial dysfunction and their correlation with disease severity. Methods and Results: This was a cross-sectional study conducted in 62 patients with CKD: 38 predialysis and 24 on hemodialysis and 50 age- and gender-matched controls. In both the patients and controls, high-sensitivity C-reactive protein (CRP) levels, %FMD, and CIMT were measured. Patients with CKD had increased CRP levels {[5.8 (1.0–6.0)] mg/L vs [1.0 (0.5–2.20)] mg/L; P < 0.001}; %FMD was significantly lower in patients on hemodialysis (5.51%) compared with stage IV (7.62%) and stage III (15.02%) and 17.95% in control subjects (P < 0.001); and CIMT values in hemodialysis patients (0.88 ± 0.06 mm) were significantly higher compared with stage IV (0.67 ± 0.10) and stage III (0.61 ± 0.12) (P < 0.001). Increased CIMT values were seen in patients with CKD (0.82 ± 0.21 mm) than in the healthy controls (0.55 ± 0.16 mm). In patients with CKD, a significant negative correlation was found between CRP levels and FMD responses (r = −0.315; P < 0.001), while a significant positive correlation was found between CRP and CIMT values (r = 0.327; P < 0.001). Compared with predialysis, hemodialysis subjects had significantly lower FMD and higher CRP and IMT values. Conclusion: CKD confers a higher inflammatory status when compared with apparently healthy general population. Abnormal FMD responses and CIMT values are more commonly found in dialysis patients. Our findings suggest that CIMT and FMD can be used as noninvasive markers for early risk assessment and stratification in various stages of CKD.

Plasmablastic lymphoma (PBL) is a distinctly rare neoplasm believed to arise from post-germinal center, terminally differentiated, activated B cells before transformation to plasma cells; and predominantly affecting human immunodeficiency virus (HIV) infected or immunodeficient males. Here, we report a rare case of primary PBL of bone marrow in an immunocompetent male, the diagnosis of which is complicated by the overlapping morphology and immunophenotype with several large cell lymphomas and plasma cell neoplasms; and showing dramatic response to anti-CD30 monoclonal antibody based therapy. We discuss the immunohistochemistry based approach and the possible diagnostic pitfalls in such cases. The inclusion of markers of plasmablastic differentiation in the diagnostic panel of large cell lymphomas is essential to avoid misclassification of these rare lymphomas.

C−H methylation of sp2 and sp3 carbon centers is significant in many biological processes. Methylated drug candidates show unique properties due to the change in solubility, conformation and metabolic activities. Several photo-catalyzed, electrochemical, mechanochemical and metal-free techniques that are widely utilized strategies in medicinal chemistry for methylation of arenes and heteroarenes have been covered in this review.

The Page kidney is a rare phenomenon. External renal parenchymal compression is the culprit. We report two cases of young males with flank pain, renal mass, and hypertension with history of blunt abdominal trauma. Initially, hypertension was controlled by angiotensin-converting enzyme (ACE) inhibitors but gradually became refractory to medical treatment. Laparoscopic nephrectomy was performed in both patients. We emphasize the Page kidney as a cause of hypertension in young patients, presenting with flank pain and renal mass with or without complications of hypertension. Management is aimed to control blood pressure by ACE inhibitors, aspiration of the hematoma, open hematoma evacuation, or nephrectomy.

Background: Yoga is proven beneficial in improving quality of life among breast cancer survivors receiving chemotherapy, but its effectiveness in lymphoma patients needs to be explored. As chemotherapy-induced neutropenia is very common among lymphoma patients, they are much prone to infections from the environment. Furthermore, trained yoga instructors are not available in every setting, so there is a need to develop home-based yoga program modules for lymphoma patients receiving chemotherapy. Aim: The aim of the study was to explore the feasibility and safety of yogic exercises among lymphoma patients during chemotherapy. Subjects and Methods: An interventional, single-arm prepost design study was conducted at a tertiary health-care center. Patients suffering from malignant lymphoma (18–65 years) with Eastern Cooperative Oncology Group performance status from 0 to 2, planned to receive chemotherapy were administered a home-based yoga program over a period of 2 months from the start of chemotherapy. The primary outcome variables were retention rate, acceptance rate, safety, and adherence. Health-related quality of life (HRQOL), fatigue level, overall sleep quality, depression, anxiety level, and pain were also assessed. Statistical Analysis: Descriptive statistics was used to see the feasibility and adherence. The paired t-test was used to compare various pre and postintervention outcome measures. Results: Fourteen patients (median age: 36 years, range13–65 years) of malignant lymphoma were enrolled in the study. Male-to-female ratio was 9:5. Non-Hodgkin's lymphoma patients constituted 64%. The recruitment rate was 93%. Favorable retention (100%), acceptability (97%), adherence (78.6%), and no serious adverse events following yoga practice were reported. Improvement was also found in HRQOL, fatigue, sleep, depression, and anxiety. However, it needs further validation in a randomized study. Conclusion: Home-based yoga program is safe and feasible among the patients suffering from malignant lymphoma receiving chemotherapy.

Purpose: The introduction of tyrosine kinase inhibitors has transformed the care of patients with chronic myeloid leukemia, with survival approaching that of healthy individuals. Current-day challenges in chronic myeloid leukemia care include adherence to tyrosine kinase inhibitor therapy. We studied adherence from resource-constrained settings and tried to analyze the factors responsible for nonadherence in these individuals. We also correlated adherence to current molecular status. Patients and Methods: This was a single-center, cross-sectional, observational study from north India. It consisted of a questionnaire-based survey in which a one-to-one interview technique was used by trained nursing staff administering the Modified Morisky Adherence Scale (MMAS-9) questionnaire. Adherence was also measured on the basis of physician’s assessment. JMP 13.0.0 was used for statistical analysis. Results: A total of 333 patients with a median age of 42 years were included in the study. The median BCR-ABL/ABL ratio (IS) was 0.175 (0.0 to 98.0). The mean MMAS-9 score was 11 ± 2. Adherence was seen in 54.95% on the basis of MMAS-9, whereas physician’s assessment reported adherence in 90.39% of patients. Using the χ2 test, no relationship was found between the two assessment techniques. There was a significant relationship between major molecular response status and adherence by physician’s assessment and MMAS-9 (P < .001). Bivariate analysis by logistic fit showed a good relation between the MMAS-9 score and the BCR-ABL/ABL ratio (IS), χ2 (1,220) = 135.45 (P < .001). On multivariate analysis, enrolment in the Novartis Oncology Access program (a patient assistance program) was significantly associated with adherence (P = .012). Conclusion: This study highlights the lack of adherence in real-world settings and the various factors responsible. Such studies are important from a public health services perspective in various settings around the world because they may lead to corrective action being taken at the institutional level.

Introduction: Various anomalous kidneys such as horseshoe kidney, crossed ectopic kidney, simple ectopic kidney, pelvic ectopic kidney, kidney with duplex system, and malrotated kidney are frequently associated with stone disease. Percutaneous nephrolithotomy (PCNL) is a challenging procedure in these patients because of abnormal orientation of kidney. Patients and Methods: Since 2005–2015, 86 patients underwent PCNL for stone removal in anomalous kidneys. Stone characteristics, type of calyceal puncture, number of punctures, need of relook procedures, mean hemoglobin drop, blood transfusion, mean operative time complications, mean hospital stay, stone free rate, and auxiliary procedure were analyzed. Results: Totally 91 sessions of PCNL was done in 86 patients including five of horseshoe kidney who had bilateral stone disease. Mean age, duration of symptoms, stone size, and hospital stay was 29.6 ± 12.6 years, 2.18 ± 1.41 years, 4.40 ± 1.16, and 4.17 ± 2.11 days, respectively. Sixteen patients underwent relook procedure, out of which only 6 could have complete stone clearance. Conclusion: PCNL in anomalous kidney is a safe and feasible procedure similar to normally located kidney, but requires careful preoperative planning and intra- and post-operative vigilance.

Aim: Transurethral resection of prostate (TURP) is considered a gold standard surgical procedure. The management of benign prostatic hyperplasia (BPH) has undergone tremendous change in recent years and shifted from open to minimal invasive procedure. With the advancement in technology and skills of surgeons, lasers have been used more liberally, particularly holmium laser. Holmium laser enucleation of prostate (HoLEP) is seen as close rival of TURP. The objective if this study is to observe long- and short-term outcomes of transurethral resection and holmium laser enucleation in the prostate of more than 60 g. Materials and Methods: This prospective randomized study includes 164 patients. Inclusion criteria were age 60 g, gross hematuria secondary to BPH, recurrent urinary tract infection, acute urinary retention, postvoid residual >150 ml, and Schafer Grade II or more. BPH associated with neurogenic bladder, stricture urethra, and carcinoma prostate were excluded from the study. Group 1 comprises patients who underwent TURP and Group 2 comprises who underwent HoLEP. Follow-up was done at 1, 3, 6, 12, and 24 months after the surgery. Results: Data of 144 patients were analyzed. The mean age of patients in TURP and HoLEP group was 66.78 ± 7.81 and 67.70 ± 7.44 years, respectively (P = 0.47), mean prostatic volume was 74.5 ± 12.56 and 75.6 ± 12.84 g, respectively (P = 0.60), operative time was 73.10 ± 10.49 and 89.56 ± 13.81 min, respectively (P = 0.0001). Mean resected tissue was 44.80 ± 9.87 and 48.49 ± 10.87, respectively (P = 0.03). The sexual function did not changed significantly in postoperative follow-up. Conclusion: HoLEP is associated with less blood loss, lower transfusion rates, and a shorter hospital stay. The disadvantage of HoLEP is longer operative time and postoperative dysuria.

Purpose: To analyze single session, intrauser reliability of a Scheimpflug device for anterior chamber (AC) and corneal parameters. Methods: In this observational study, 100 normal candidates underwent Scheimpflug analysis with Sirius 3D Rotating Scheimpflug Camera and Topography System (Costruzione Strumenti Oftalmici, Italy). Two scans in dark room conditions were performed by the same experienced user. The candidates were asked to keep both eyes closed for 5 min before the scans. Exclusion criteria were previous ocular surgery, corneal scarring and anterior segment/posterior segment anomalies. Only the right eyes were used for the analysis. Both corneal (central, minimum, and apical thickness, volume, horizontal visible iris diameter, and apical curvature) and anterior chamber (volume, depth, angle, horizontal diameter) measurements were evaluated. Results: There was no difference in the means of repeated measurements (p > 0.05, ANOVA). Intraclass correlations between the measures were high and ranged from 0.995–0.997 for corneal to 0.964–0.997 for anterior chamber (AC) parameters. The precision of repeatability measures (1.96 × Sw) was approximately 5 μ for the central and minimum corneal thickness, 8 μ for the apical corneal thickness, 0.06 mm for AC (anterior chamber) depth and less than 2° for the AC angle. Conclusions: Sirius Scheimpflug system has high repeatability for both corneal and AC parameters in normal eyes.

A young man presented with irritative lower urinary tract symptoms and multiple fistulae (watering can) in the perineum since 6 months. Micturating cystourethrogram and retrograde urethrogram was performed after 12 weeks following suprapubic cystostomy which showed bulbar urethral stricture with multiple urethrocutaneous fistulae. He underwent anastomotic urethroplasty and excision of the urethrocutaneous fistulae. Histopathology of the excised fistulous tract showed granulomatous pathology suggestive of tuberculosis. Antitubercular treatment was given for 9 months. The patient is voiding well at 12 months follow-up.

Paraurethral cyst is a benign cystic disorder of anterior vaginal wall. Many secondary complications have been described in literature, but stone formation in the cyst is a rare phenomenon. We are reporting a case of a 35-year-old multiparous woman who presented with lower urinary tract symptoms, dysuria, and dyspareunia. She was diagnosed as a case of the paraurethral cyst with stones and was managed successfully. Various differential diagnoses have been suggested, most important being urethral diverticulum, ruled out by urethroscopy. Many imaging modalities have been described, but physical examination plays the key role in reaching the diagnosis of stone. For definitive management incision over the cyst with stone removal followed by marsupialization is performed to prevent recurrence.

Hydatid disease of the adrenal gland is uncommon. We present images and description a case of emphysematous hydatid cyst of the adrenal gland that had an unfavourable intraoperative outcome.

Letter to the Editor

ABSTRACT Introduction For dorsal onlay graft placement, unilateral urethral mobilization is less invasive than standard circumferential urethral mobilization. Apart from success in terms of patency of urethra, other issues like sexual function, overall quality of life and patient satisfaction remain important issues while comparing outcomes of urethroplasty. Aim To prospectively compare the objective as well as subjective outcomes of two approaches. Materials and Methods Between July 2011 and January 2015, 136 adult males having anterior urethral stricture with urethral lumen ≥ 6 Fr. were prospectively assigned between two groups by alternate randomization. Operative time, complications, success rate (no obstructive symptoms, no need of any postoperative intervention, Q max > 15mL/sec), sexual functions (using Brief Male Sexual Function Inventory) were compared. Results Baseline parameters were similar in both groups (68 in each group). Overall success rate was similar in both groups (89 % and 91 % respectively). Improvement in total LUTS scores was similar in groups. Changes in overall health status (VAS and EQ 5D) was equal in both groups. Erectile function score was significantly decreased in DO than DL group while ejaculatory function and sexual desire remained stable after urethroplasty in both groups. Conclusions In anterior urethral stricture buccal mucosa graft provides satisfactory results as onlay technique. No technique whether dorsolateral and dorsal techniques is superior to other. Dorsolateral technique needs minimal urethral mobilization and should be preferred whenever feasible.

ABSTRACT Objective: To analyse outcomes of holmium laser and pneumatic lithotripsy in treatment of lower ureteric calculus in pediatric patients. Materials and methods: Prospective study conducted between August 2013 and July 2015. Inclusion criteria were lower ureteric calculus with stone size ≤1.5cms. Exclusion criteria were other than lower ureteric calculus, stone size ≥1.5cms, congenital renal anomalies, previous ureteral stone surgery. Patients were divided into two groups. Group A underwent pneumatic and group B underwent laser lithotripsy procedure. Patient's baseline demographic and peri-operative data were recorded and analysed. Post operatively X-ray/ultrasound KUB (Kidney, ureter and bladder) was performed to assess stone free status. Results: A total of 76 patients who met the inclusion criteria to ureteroscopic intracorporeal lithotripsy were included. Group A and B included 38 patients in each. Mean age was 12.5±2.49 in Group A and 11.97±2.74 years in Group B respectively (p=0.38). Overall success rate was 94.73% in Group A and 100% in Group B, respectively (p=0.87). Conclusion: Holmium Laser lithotripsy is as efficacious as pneumatic lithotripsy and can be used safely for the endoscopic management of lower ureteric calculus in pediatric patients. However, holmium laser requires more expertise and it is a costly alternative.

In complex crystals close to melting or at finite temperatures, different types of defects are ubiquitous and their role becomes relevant in the mechanical response of these solids. Conventional elasticity theory fails to provide a microscopic basis to include and account for the motion of point defects in an otherwise ordered crystalline structure. We study the elastic properties of a point-defect rich crystal within a first principles theoretical framework derived from the microscopic equations of motion. This framework allows us to make specific predictions pertaining to the mechanical properties that we can validate through deformation experiments performed in molecular dynamics simulations. [ABSTRACT FROM AUTHOR]

The present study examines the flow and thermal characteristics of a tube containing perforated conical inserts by varying the Reynolds number in the range of 4000–20000. The perforated conical insert having (d/D) ratio of 0.3, (p/D) ratio of 2, (x/L) ratio of 0.25, and N = 6 showed the minimum entropy generation. Second law analysis showed that the solid inserts of a lower pitch to diameter ratio are suitable to transfer high energy transfer at lower Reynold's number, whereas the perforated conical inserts are found to be effective at higher Reynolds numbers. Empirical correlations are developed for solid and perforated conical inserts. [ABSTRACT FROM AUTHOR]

Diabetic myonecrosis or muscle infarction (DMI), a clinicoradiological entity is an underdiagnosed complication of diabetes mellitus. It refers to spontaneous aseptic necrosis of skeletal muscles commonly of the lower limb without evidence of any large vessel disease. It presents as painful swollen limb without any external insult in patients with long-standing diabetes mellitus with other microvascular complications especially nephropathy. We present four instances of DMI in our patients who had end-stage renal disease with a varied course. [ABSTRACT FROM AUTHOR]

Molecular dynamics computer simulations of a binary Lennard-Jones glass under shear are presented. The mechanical response of glassy states having different thermal histories is investigated by imposing a wide range of external shear rates, at different temperatures. The stress-strain relations exhibit an overshoot at a strain of around 0.1, marking the yielding of the glass sample and the onset of plastic flow. The amplitude of the overshoot shows a logarithmic behavior with respect to a dimensionless variable, given by the age of the sample times the shear rate. Dynamical heterogeneities having finite lifetimes, in the form of shear bands, are observed as the glass deforms under shear. By quantifying the spatial fluctuations of particle mobility, we demonstrate that such shearbanding occurs only under specific combinations of imposed shear-rate, age of glass, and ambient temperature. [ABSTRACT FROM AUTHOR]

Under external mechanical loading, glassy materials, ranging from soft matter systems to metallic alloys, often respond via formation of inhomogeneous flow patterns, during yielding. These inhomogeneities can be precursors to catastrophic failure, implying that a better understanding of their underlying mechanisms could lead to the design of smarter materials. Here, extensive molecular dynamics simulations are used to reveal the emergence of heterogeneous dynamics in a binary Lennard-Jones glass, subjected to a constant strain rate. At a critical strain, this system exhibits for all considered strain rates a transition towards the formation of a percolating cluster of mobile regions. We give evidence that this transition belongs to the universality class of directed percolation. Only at low shear rates, the percolating cluster subsequently evolves into a transient (but long-lived) shear band with a diffusive growth of its width. Finally, the steady state with a homogeneous flow pattern is reached. In the steady state, percolation transitions also do occur constantly, albeit over smaller strain intervals, to maintain the stationary plastic flow in the system. [ABSTRACT FROM AUTHOR]

Cytotoxic drugs are highly efficacious and also have low therapeutic index. A great degree of caution needs to be exercised in their usage. To optimize the efficacy these drugs need to be given at maximum tolerated dose which leads to significant amount of toxicity to the patient. The fine balance between efficacy and safety is the key to the success of cytotoxic chemotherapeutics. However, it is possibly more rewarding to obtain that balance for this class drugs as the frequency of drug related toxicities are higher compared to the other therapeutic class and are potentially life threatening and may cause prolonged morbidity. Significant efforts have been invested in last three to four decades in therapeutic drug monitoring (TDM) research to understand the relationship between the drug concentration and the response achieved for therapeutic efficacy as well as drug toxicity for cytotoxic drugs. TDM evolved over this period and the evidence gathered favored its routine use for certain drugs. Since, TDM is an expensive endeavor both from economic and logistic point of view, to justify its use it is necessary to demonstrate that the implementation leads to perceivable improvement in the patient outcomes. It is indeed challenging to prove the utility of TDM in randomized controlled trials and at times may be nearly impossible to generate such data in view of the obvious findings and concern of compromising patient safety. Therefore, good quality data from well-designed observational study do add immense value to the scientific knowledge base, when they are examined in totality, despite the heterogeneity amongst them. This article compiles the summary of the evidence and the best practices for TDM for the three cytotoxic drug, busulfan, 5-FU and methotrexate. Traditional use of TDM or drug concentration data for dose modification has been witnessing a sea change and model informed precision dosing is the future of cytotoxic drug therapeutic management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Smita, Narayan, J and Gaurav.)

Background: Sealer penetration into dentinal tubules eliminates the pathways for bacterial leakage and entombs intratubular bacteria., Aim: The aim of this study was to evaluate and compare the depth of radicular dentinal tubule penetration of five root canal sealers using confocal laser scanning microscopy., Methods: Fifty freshly extracted single-rooted maxillary anterior teeth were used. After decoronation at the cementoenamel junction, they were prepared to ProTaper size F3. After irrigation with 5 mL smear clear, 5 mL 5% sodium hypochlorite and 5 mL distilled water alternatively, the samples were randomly divided into five groups ( n = 10) and obturated by lateral compaction technique using the test sealers labeled by fluorescent rhodamine B dye (Mayor Diagnostics, Mumbai, India). Zinc oxide eugenol (ZOE) (Prime Dental Products), EndoREZ (Ultradent), Sealapex (SybronEndo), AH Plus (Dentsply Maillefer), and MTA-Fillapex (Angelus) formed the test groups. Teeth were then positioned in blocks of orthodontic resin. Three horizontal sections of 1-mm representing coronal middle and apical thirds were made and examined with Zeiss (laser scanning microscope [LSM] 780) confocal LSM. Images were analyzed using ZEN 2.1 software., Statistical Analysis: Data were recorded and subjected to statistical analysis using one-way ANOVA test., Results: Maximum penetration depth was demonstrated by AH Plus in the coronal and apical thirds, MTA-Fillapex in the middle thirds, while minimum penetration depth was seen in ZOE in the coronal and middle thirds and Sealapex in the apical thirds. None of the root canal sealers were able to penetrate the complete depth of radicular dentinal tubules., Conclusion: While AH Plus and MTA-Fillapex showed the highest penetration into radicular dentinal tubules, ZOE and Sealapex demonstrated the least penetration., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Conservative Dentistry.)

Background  Prognosis of gallbladder cancer (GBC) has not changed in the past 20 years. Comprehensive genomic profiling (CGP) carries potential to determine the actionability for multiple targets, including ERBB2 , ERBB3 , MET , ROSI , FGFR , and PIK3 . This study evaluates the role of CGP and targeted therapies. Methods  This is a multicenter, prospective, single-arm study. All consecutive patients of unresectable and/or metastatic GBC of age ≥18 years were enrolled. Hybrid capture-based CGP was performed by Foundation Medicine CDx. All patients received first-line chemotherapy with gemcitabine-cisplatin regimen. Patients with ERBB2/3 amplification received trastuzumab with capecitabine or nab-paclitaxel, and patients with MET amplification were treated with crizotinib. For ERBB2/3 mutations, lapatinib plus capecitabine regimen was used. Results  Fifty patients were studied with a median age of 56 years (range 26-83) and a male-to-female ratio of 1:1.6. ERBB2 and ERBB3 amplification was seen in 9 (18%) and 2 (4%) patients, respectively. Four patients with ERBB2 amplification received trastuzumab and/or lapatinib, showed partial response, and maintained response beyond 12 weeks. One patient had mixed response, whereas two patients progressed on trastuzumab and lapatinib. Three patients with ERBB3 mutations showed response to lapatinib-capecitabine. One patient with MET amplification responded to crizotinib for 4 weeks. PIK3 mutations were present in 14% of cases and were independent of ERBB aberrations. Conclusion  GBC is enriched in 28% of patients with ERBB2 and ERBB3 amplifications and/or mutations. Responses are seen with lapatinib in concurrent ERBB2 mutation and amplification. ERBB3 mutation showed response to lapatinib. MET and PIK3 are new findings in GBC, which may be targeted., Competing Interests: Conflicts of Interest There are no conflicts of interest., (MedIntel Services Pvt Ltd. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: Chronic kidney disease (CKD) predisposes to accelerated atherosclerosis that is measured by carotid artery intima media thickness (CIMT) and brachial artery flow-mediated dilation (FMD). The aim of this study was to assess the noninvasive risk markers of subclinical atherosclerosis and endothelial dysfunction and their correlation with disease severity., Methods and Results: This was a cross-sectional study conducted in 62 patients with CKD: 38 predialysis and 24 on hemodialysis and 50 age- and gender-matched controls. In both the patients and controls, high-sensitivity C-reactive protein (CRP) levels, %FMD, and CIMT were measured. Patients with CKD had increased CRP levels {[5.8 (1.0-6.0)] mg/L vs [1.0 (0.5-2.20)] mg/L; P < 0.001}; %FMD was significantly lower in patients on hemodialysis (5.51%) compared with stage IV (7.62%) and stage III (15.02%) and 17.95% in control subjects ( P < 0.001); and CIMT values in hemodialysis patients (0.88 ± 0.06 mm) were significantly higher compared with stage IV (0.67 ± 0.10) and stage III (0.61 ± 0.12) ( P < 0.001). Increased CIMT values were seen in patients with CKD (0.82 ± 0.21 mm) than in the healthy controls (0.55 ± 0.16 mm). In patients with CKD, a significant negative correlation was found between CRP levels and FMD responses ( r = -0.315; P < 0.001), while a significant positive correlation was found between CRP and CIMT values ( r = 0.327; P < 0.001). Compared with predialysis, hemodialysis subjects had significantly lower FMD and higher CRP and IMT values., Conclusion: CKD confers a higher inflammatory status when compared with apparently healthy general population. Abnormal FMD responses and CIMT values are more commonly found in dialysis patients. Our findings suggest that CIMT and FMD can be used as noninvasive markers for early risk assessment and stratification in various stages of CKD., Competing Interests: There are no conflicts of interest.

Purpose: The introduction of tyrosine kinase inhibitors has transformed the care of patients with chronic myeloid leukemia, with survival approaching that of healthy individuals. Current-day challenges in chronic myeloid leukemia care include adherence to tyrosine kinase inhibitor therapy. We studied adherence from resource-constrained settings and tried to analyze the factors responsible for nonadherence in these individuals. We also correlated adherence to current molecular status., Patients and Methods: This was a single-center, cross-sectional, observational study from north India. It consisted of a questionnaire-based survey in which a one-to-one interview technique was used by trained nursing staff administering the Modified Morisky Adherence Scale (MMAS-9) questionnaire. Adherence was also measured on the basis of physician's assessment. JMP 13.0.0 was used for statistical analysis., Results: A total of 333 patients with a median age of 42 years were included in the study. The median BCR-ABL/ABL ratio (IS) was 0.175 (0.0 to 98.0). The mean MMAS-9 score was 11 ± 2. Adherence was seen in 54.95% on the basis of MMAS-9, whereas physician's assessment reported adherence in 90.39% of patients. Using the χ 2 test, no relationship was found between the two assessment techniques. There was a significant relationship between major molecular response status and adherence by physician's assessment and MMAS-9 ( P < .001). Bivariate analysis by logistic fit showed a good relation between the MMAS-9 score and the BCR-ABL/ABL ratio (IS), χ 2 (1,220) = 135.45 ( P < .001). On multivariate analysis, enrolment in the Novartis Oncology Access program (a patient assistance program) was significantly associated with adherence ( P = .012)., Conclusion: This study highlights the lack of adherence in real-world settings and the various factors responsible. Such studies are important from a public health services perspective in various settings around the world because they may lead to corrective action being taken at the institutional level.