Comparative Evaluation of Topographic Parameters Using Three Different Topographers in Keratoconic and Cross-linked Keratoconic Corneas.

PURPOSE: To compare the parameters of three different topographic devices (Pentacam HR, Oculus Optikgeräte GmbH; Sirius, Costruzione Strumenti Oftalmici; and Cassini, i-Optics) in grading the severity of keratoconus in cross-linked and non-cross-linked eyes. METHODS: This was a prospective comparative interventional study done in a tertiary eye care center, wherein 114 eyes of 68 patients with keratoconus were divided into two groups: 62 eyes that were observed and 52 eyes that were cross-linked. All eyes were evaluated on all three topographers at baseline, 3-month follow-up, and 6-month follow-up. RESULTS: The Sirius showed significantly lower values of mean flat keratometry in comparison to the Pentacam HR (limits of agreement [LoA]: 1.75 to 3.51%) and Cassini (LoA: 1.75 to 3.51%). The mean steep keratometry values were higher for the Cassini in comparison to the Pentacam HR (LoA: 4.39 to 7.02%) and Sirius (LoA: 3.51 to 6.14%). The mean steep keratometry values of the Sirius were significantly lower than those of the Pentacam HR and in both the cross-linked and observation groups (LoA: 3.51 to 6.14%). The mean keratometry values were significantly higher in the Cassini compared to the Pentacam HR (LoA: 3.51 to 8.77%) and significantly lower in the Sirius in comparison to the Pentacam HR (LoA: 3.51 to 6.14%). The mean difference in astigmatism was also statistically significant between the three tomographers in both groups, with the Cassini showing higher values (LoA: 3.51 to 5.26%) and the Sirius lower values than the Pentacam HR (LoA: 5.26 to 6.14%). CONCLUSIONS: The authors conclude the three devices cannot be used interchangeably. The Cassini showed better agreement and correlation with the Pentacam HR in the staging of keratoconus, whereas the Sirius tended to underdiagnose and under-stage the disease. [J Refract Surg. 2024;40(4):e260-e269.].

Thiopurines Have Sustained Long-term Effectiveness in Patients with Inflammatory Bowel Disease, Which is Independent of Disease Duration at Initiation: A Propensity Score Matched Analysis.

BACKGROUND AND AIMS: Thiopurines are viable option for the treatment of inflammatory bowel disease [IBD] in resource-limited countries. However, data on the effect of disease duration at thiopurines initiation on long-term effectiveness are limited. METHOD: We performed a propensity matched analysis of a retrospective cohort of patients with ulcerative colitis [UC] and Crohn's disease [CD]. Patients initiated on thiopurines early in the disease course [≤2 years] were compared with those started late [>2 years]. Effectiveness was defined as no requirement for hospitalisation, anti-tumour necrosis factor [TNF] agents, or surgery, and minimum steroid requirement [≤1 steroid course in 2 years] during follow-up. RESULTS: A total of 988 [UC: 720, CD: 268] patients were included (male: 665 [60.8%], median age: 40 [32-51] years, median follow-up: 40 [19-81] months). Overall effectiveness at 5 and 10 years was 79% and 72% in UC, and 69% and 63% in CD, respectively. After propensity score matching, there was no difference in 5- and 10-year effectiveness between early and late thiopurine initiation groups either for UC [81% and 80% vs 82% and 74%; p = 0.92] or CD [76% and 66% vs 72% and 51%, p = 0.32]. Male sex for UC (negative: hazard ratio [HR]: 0.67, 95% confidence interval [CI): 0.45-0.97; p = 0.03), and ileal involvement [positive: HR: 3.03, 95% CI: 1.32-6.71; p = 0.008], steroid-dependent disease [positive: HR: 2.70, 95% CI: 1.26-5.68; p = 0.01] and adverse events [negative: HR: 0.47, 95% CI:0.27-0.80; p = 0.005] for CD were predictors of thiopurine effectiveness. CONCLUSION: Thiopurines have sustained long-term effectiveness in both UC and CD. However, early thiopurine initiation had no better effect on long-term disease outcome compared with late initiation.

A randomized controlled trial to explore the safety and efficacy of irradiated buffy-coat granulocytes in pediatric patients with febrile neutropenia.

BACKGROUND: Transfusion of granulocytes obtained by apheresis is beneficial in febrile neutropenia (FN) but expensive and time-consuming. Buffy-coat-derived granulocytes could be an alternative. We studied the efficacy and safety of the administration of irradiated buffy-coat-derived granulocytes along with the standard of care in pediatric high-risk (HR) FN. METHODS: Sixty children ≤18 years with malignancy and chemotherapy-induced HR FN were randomized to either the granulocyte transfusion (GT) arm which received irradiated buffy-coat derived granulocyte transfusion along with the standard treatment or the standard treatment (ST) arm. RESULTS: Baseline characteristics, day-to-defervescence, antibiotic duration, hospital stay, and mortality were comparable between the groups. A significant difference was seen in days to achieve absolute neutrophil count (ANC) >500/mm3 in the 2 groups: 4.5 days (3-6.5) in the GT arm v/s 8 days (4-11) in the ST arm (P=0.01). CONCLUSION: Buffy-coat-derived granulocyte transfusion was safe and led to early hematological recovery but was not associated with survival benefits. Future studies with earlier initiation in the intended dose could be undertaken to generate more evidence.

The Utility of Galactomannan and Polymerase Chain Reaction Assays in Bronchoalveolar Lavage for Diagnosis of Chronic Pulmonary Aspergillosis.

The diagnosis of chronic pulmonary aspergillosis (CPA) is established by combined clinic-radio-microbiological criteria. Out of the different microbiological criteria, a positive serology for Aspergillus-specific IgG levels is the cornerstone of diagnosis. Alternatively, other microbiological evidence are sometimes sought viz., positive Aspergillus antigen (broncho-alveolar lavage fluid, i.e., BALF galactomannan ≥ 1.0), histopathological demonstration of the fungi following lung biopsy or resection, demonstration of hyaline septate hyphae in direct microscopy resembling Aspergillus spp. or its growth on a respiratory specimen. However, the exact roles of BALF- GM and the newer BALF-PCR have not been confirmed by studies till date. This study enrolled 210 patients with suspected CPA. Of the participants, 88 patients met the criteria for CPA, whereas 122 patients had an alternative diagnosis. The sensitivity-specificity of AsperGenius® PCR and "in-house" PCR were 52.27(36.69-67.54) %-33.78 (23.19-45.72) % and 36.36 (22.41-52.23) %-39.19 (28.04-51.23) % respectively. The sensitivity/specificity of BALF (> 1.0) and serum galactomannan (> 1.0) were 46.55% (33.34-60.13)/64.08% (54.03-73.3) and 29.82% (22.05-37.6)/86.84% (81.1-92.59) respectively. The optimal cut-off values for BALF-Galactomannan and serum galactomannan in diagnosing CPA were found to be 0.69 (sensitivity: 64%; specificity: 53%) and 0.458 (sensitivity: 67%; specificity: 64%) respectively. This results of this study suggests that Aspergillus PCR from BAL may not be a good "rule-in" test for diagnosing CPA. While the performances of GM in BAL and serum may be better than PCR, it should be best used in conjunction with other clinical, radiological, and other microbiological characteristics.

Biocompatible dressing for pediatric hypospadias repair.

PURPOSE: The search for an ideal Hypospadias repair dressing continues. We aimed to develop a hypoallergenic optimized biocompatible dressing (BD). METHOD: BD with a multi-layered structure of hydrophilic treated Polypropylene with three-layered technologies; Absorbent-spunlaced hydroentangled polyester/viscose blend, outer Polypropylene, Polyester, Acrylic, and Spandex, with super Absorbent Polymer and Acrylic adhesive. Wistar rat abdominal wound model was divided into two groups: control (normal gauze dressing with adhesive) and Study (BD). The physical properties and wound characteristics were compared. RESULTS: Average mass: thickness of BD was 626.7 ± 5.6 g m-2: 2.6 ± 0.015 mm. Absorption was 1425.2 ± 127.6%. Percentage desorption of solution A from dressings at 24:40 h was 1249 ± 150%:1417 ± 230%. BD was hydrophilic with no particles/residue after immersion and pH neutral. The average air permeability was 11.6 ± 1.6 cm3/cm2/sec. The tensile force was 200N-220N with an extension on the breaking point at 24 mm. BD was superior for ease of removability on Day 6 (p = 0.012) and sticking quality (p = 0.036), absorption (p = 0.036), ease of removability(p = 0.036), and sustenance (p = 0.030) on Day 10. BD dressing demonstrated better wound healing (p = 0.015) and decreased redness (p = 0.002) on Day 10. Histopathological healing was better with BD on Day 14(p = 0.025) and Day 20 (p = 0.034). CONCLUSION: BD demonstrated better desirable physical and wound healing qualities with less inflammation compared with control normal dressing.

CD34 negative HLA-DR negative acute myeloid leukaemia: A higher association with NPM1 and FLT3-ITD mutations.

INTRODUCTION: CD34 and HLA-DR negativity is often used as a characteristic immunophenotypic feature of acute promyelocytic leukaemia (APL) that differentiates APL from other subtypes of acute myeloid leukaemia (AML). However, other subtypes of AML, without expression of CD34 and HLA-DR antigens, have also been reported. METHODS: We analysed the HLA-DR negative de novo non-APL AML cases by dividing HLA-DR negative non-APL group into 2 sub-groups based on CD34 expression and compared the characteristics of CD34 negative HLA-DR negative with CD34 positive HLA-DR negative non-APL AML cases with respect to morphologic, immunophenotypic, molecular and clinical parameters. RESULTS: There were 70 cases (8.54%) which were CD34 negative HLA-DR negative and 52 cases (6.34%) were CD34 positive HLA-DR negative. The median age at diagnosis was higher in CD34 negative HLA-DR negative AML than in CD34 positive HLA-DR negative AML group (38 years vs. 12 years, p < 0.001). DIC rate was higher in CD34 negative HLA-DR negative group than the other group (p < 0.001). Median total leucocyte count was higher with higher blast count in peripheral blood and bone marrow in CD34 negative HLA-DR negative AML cases than the other group (p < 0.05). CD34 negative HLA-DR negative AML was more associated with normal karyotype (96.2% vs. 38.5%; p < 0.001), NPM1 mutation (67.8% vs. 8.3%; p < 0.001) and FLT-ITD mutation (37.3% vs. 13.9%; p < 0.05). In CD34 negative HLA-DR negative group, 16 cases had co-occurrence of NPM1 and FLT3-ITD mutations, whereas no case of CD34 positive HLA-DR negative group had such dual mutation positivity. There was poor median overall survival [3.8 months (95%CI: 2.3-7.8 months) vs. 20.4 months (95% CI: 12.8-25.7 months); p = 0.0148] in CD34 positive HLA-DR negative AML than CD34 negative HLA-DR negative AML cases. CONCLUSION: We found that the CD34 negative HLADR negative non APL AML is highly associated with NPM1 and FLT3-ITD mutation, older age at diagnosis, DIC, higher total leucocyte count, higher blast counts and normal karyotype in comparison to CD34 positive HLA-DR negative AML group. Co-occurrence of NPM1 and FLT3-ITD mutation was also exclusively seen in CD34 negative HLA-DR negative group. There was poor overall survival in CD34 positive HLA-DR negative AML than CD34 negative HLA-DR negative AML cases.

Clinico-Hematological Profile of Acute Myeloid Leukemia: Experience From a Tertiary Care Cancer Center in North India.

INTRODUCTION: Complete diagnosis of acute myeloid leukemia (AML) requires knowledge of clinical information combined with morphologic evaluation, immunophenotyping, karyotyping, and molecular genetic testing. The study intends to evaluate the demographic profile, clinical workup, and investigation, including flow cytometric immunophenotyping, in adult and pediatric age groups of AML. MATERIALS AND METHODS: This is a retrospective study of AML patients treated between January 2017 and December 2021. Clinical and demographic characteristics and investigation findings were recorded from case files and the hematology database. RESULT: A total of 896 cases of AML were registered during the given period, of which 819 cases were de-novo AML. Among those 819 cases, more than two-thirds of cases, i.e., 78.9% (N = 646), received induction chemotherapy. A significantly higher male-to-female ratio was observed (1.5:1). The median age was 22 years. The median time for diagnosis was three days and the median time for treatment intervention was four days. There were significant differences in the Eastern Cooperative Oncology Group (ECOG) performance status scores between pediatric and adult AML patients. Pediatric AML patients presented with better ECOG performance scores (ECOG performance scores 0 and 1) than adult patients (74.76% vs. 43.14%, p < 0.001). Further comparing adult vs. pediatric AML patients, normal karyotype (60.56% vs. 31.93%, p < 0.001) and NPM1 (22.25% vs. 6.72%, p < 0.001) and FLT3-ITD mutations (20.28% vs. 7.98%, p<0.001) were more common in the adult group, whereas AML-ETO (40.76% vs. 16.34%, p < 0.001) was more common in the pediatric group. CONCLUSION: The study highlights the presenting age is lower than global figures. The median time for initial diagnosis and the start of treatment is within the acceptable norms. Normal karyotype and NPM1 and FLT3 mutations were common in adult AML patients, whereas AML-ETO was more common in the pediatric cohort. These findings will help plan prospective studies and see the correlation with treatment outcomes. The laboratory workup practice currently complies with the standard guidelines at our center.

Effect of the sequence of pull of bone marrow aspirates on plasma cell quantification in plasma cell proliferative disorders.

INTRODUCTION: The evaluation of plasma cell (PC) compartment is influenced by the quality of bone marrow aspirate (BMA). Herein, we evaluated the impact of sequence of pull on quality of clinical assessment in plasma cell proliferative disorders (PCPDs). METHODS: Histomorphology along with smears from first pull and second pull BMA and flow cytometric immunophenotyping (FCMI) data from second pull aspirate were evaluated for cellularity and PC%. RESULTS: Of the 484 samples, BMA smears were adequate in 87.4% of first pull (median PC = 7%; IQR = 2-25%) and 51.2% of second pull samples (median PC = 2%; IQR = 0.5-12%; p < 0.001). Recovery of PC was least on FCMI (median PC = 0.59%; IQR = 0.14-3.07%), however, sample adequacy was met in 42.6% of samples with acquisition of ≥3 million events. Second pull smears under-reported PC% in 34% of newly diagnosed multiple myeloma (NDMM) (<10% PC) and 46% of MM on therapy (<5% PC), resulting in suboptimal assessment. Bone marrow biopsy (BMBx) was evaluated in a total of 309 cases (median PC = 10.0%; IQR 4.0-40.0%) with significantly higher numbers of BMPC% on BMBx compared with first pull smears (Mean ± 2SD: 25.9% ± 30.54 vs. 20.77% ± 20.20; p = 0.001). CONCLUSION: First pull BMA smears were of superior quality but inadequate in one-tenth of samples. Second pull smears underreported PC% and recovery of PC compartment was poorest on FCMI. Concurrent bone marrow biopsy and use of the first pull sample for FCMI along with acquisition of a higher number of cells on FCMI may enhance the quality of assessment in PCPDs.

Histologic Changes in Core-Needle Liver Biopsies From Patients With Acute-on-Chronic Liver Failure and Independent Histologic Predictors of 28-Day Mortality.

CONTEXT.­: The histologic features in patients with acute-on-chronic liver failure (ACLF) are evolving, and histologic indicators of patients' poor prognosis are not yet fully established. OBJECTIVE.­: To evaluate the independent histologic predictors of 28-day mortality in ACLF patients on core-needle liver biopsies. DESIGN.­: Core-needle biopsies from patients with a diagnosis of ACLF (n = 152) as per the European Association for the Study of the Liver criteria were included during 8 years. Liver biopsies from 98 patients with compensated chronic liver disease were included as disease controls for histologic comparison. Features of ongoing changes, such as hepatic necrosis, hepatic apoptosis, cholestasis, hepatocyte degeneration, bile ductular proliferation, Mallory-Denk bodies, steatosis, and extent of liver fibrosis, were analyzed for predicting short-term mortality (28 days). A P value of <.05 was considered significant. RESULTS.­: In our cohort of ACLF patients, the following etiologies for acute decompensation were identified: alcohol, 47 of 152 (30.9%); sepsis, 24 of 152 (15.7%); hepatotropic viruses, 20 of 152 (13.1%); drug-induced liver injury, 11 of 152 (7.2%); autoimmune flare, 9 of 152 (5.9%); mixed etiologies, 5 of 152 (3.2%); and cryptogenic, 36 of 152 (23.6%). On histologic examination, hepatic necrosis (P < .001), dense lobular inflammation (P = .03), cholestasis (P < .001), ductular reaction (P = .001), hepatocyte degeneration (P < .001), and absence of advanced fibrosis stages (P < .001) were identified significantly more othen in ACLF patients than in disease controls on univariate analysis. On multivariate Cox regression analysis, the absence of advanced Ishak histologic activity index fibrosis stages (P = .02) and the presence of dense lobular inflammation (P = .04) were associated with increased 28-day mortality in ACLF patients. After adjusting the clinical causes of acute decompensation, only dense lobular inflammation was found as an independent predictor of short-term mortality (P = .04) in ACLF patients. CONCLUSIONS.­: Dense lobular necroinflammatory activity is a clinically independent histologic predictor of 28-day short-term mortality in patients with ACLF.

Circulatory GSK-3ß: Blood-Based Biomarker and Therapeutic Target for Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is the progressive brain disorder which degenerates brain cells connection and causes memory loss. Although AD is irreversible, it is not impossible to arrest or slow down the progression of the disease. However, this would only be possible if the disease is diagnosed at an early stage, and early diagnosis requires clear understanding of the pathogenesis at molecular level. Overactivity of GSK-3ß and p53 accounts for tau hyperphosphorylation and the formation of amyloid-ß plaques. OBJECTIVE: Here, we explored GSK-3ß and p53 as blood-based biomarkers for early detection of AD. METHODS: The levels of GSK-3ß, p53, and their phosphorylated states were measured using surface plasmon resonance and verified using western blot in serum from AD, mild cognitive impairment (MCI), and geriatric-control (GC) subjects. The neurotoxic SH-SY5Y cell line was treated with antioxidant Emblica Officinalis (EO) for rescue effect. RESULTS: GSK-3ß, p53, and their phosphorylated states were significantly over expressed (p > 0.001) in AD and MCI compared to GC and can differentiate AD and MCI from GC. The expression level of GSK-3ß and p53 proteins were found to be downregulated in a dose-dependent manner after the treatment with EO in amyloid-b-induced neurotoxic cells. CONCLUSION: These proteins can serve as potential blood markers for the diagnosis of AD and EO can suppress their level. This work has translational value and clinical utility in the future.

A comprehensive analysis of cytogenetics, molecular profile, and survival among pediatric acute myeloid leukemia: a prospective study from a tertiary referral center.

BACKGROUND AND AIMS: The objectives of this study were to investigate the cyto-molecular profile and survival of pediatric acute myeloid leukemia (AML). METHODS: This prospective study was carried out in a tertiary care hospital from October 2018 to December 2020. Karyotype and cytogenetics analyses were done to identify chromosomal aberrations in pediatric AML. The targeted molecular panel utilized the polymerase chain reaction (PCR), reverse transcription-polymerase chain reaction (RT-PCR), and fragment analysis. RESULTS: A total of 70 patients of AML with aged ≤18 years were enrolled in this study. The cytogenetic analyses revealed abnormal/recurrent cytogenetic abnormalities (CA) in 64.3% of patients and normal cytogenetics (CN) in 35.7% of patients. FAB M2 subtype showed frequent aberrant expression of the CD19 marker. CD7, CD11b, and CD36a were significantly present in the absence of molecular markers. Common chromosomal abnormalities were t(translocation) (8;21) (55%), monosomy/deletion 7 (13%), monosomal karyotype (5%) and complex karyotype (3%). The fusion transcripts RUNX1-RUNX1T1 [t(8;21)] (41%) and CBFB-MYH11 [t(16;16)] (3%) were detected by RT-PCR and FLT3-TKD D835 mutation (1.5%) by allele-specific oligo PCR. Fragment analysis revealed NPM1 (8%) mutation and FLT-ITD (9.5%) mutations. Complete remission was achieved in all evaluable patients. The median follow-up period of our patients was 225 days (IQR 28; 426 days). The median event-free survival (EFS) in all patients was 11.9 months (95% CI, 5-12.6 months). The forty months overall survival probability (pOS) was 58% in all patients. CONCLUSION: The majority of patients had abnormal/recurrent cytogenetics abnormalities. FAB M2 subtype showed frequent aberrant expression of the CD19. The absence of molecular markers may suggest the presence of CD7, CD11b, and CD36a expression. The overall survival has increased considerably in LMIC.

Modified ultrafiltration and postoperative course in patients undergoing repair of tetralogy of fallot.

BACKGROUND: Expected benefits of modified ultrafiltration (MUF) include increased hematocrit, reduction of total body water and inflammatory mediators, improved left ventricular systolic function, and improved systolic blood pressure and cardiac index (CI) following cardiopulmonary bypass (CPB). This prospective randomized trial tested this hypothesis. METHODS: Seventy-nine patients undergoing intracardiac repair of tetralogy of fallot were randomized to conventional ultrafiltration (CUF) + MUF (n = 39) or only CUF group (n = 40). The primary outcome was a change in hematocrit. Secondary outcomes were changes in peak airway pressures, ventilatory support, blood transfusions, time to peripheral rewarming, mean arterial pressure, central venous pressure, inotrope score (IS), and CI. Serum inflammatory markers were measured. RESULTS: Baseline hematocrit was 50.6 ± 10.02 in the only CUF group whereas it was 43.9 ± 5.55 in the CUF + MUF group (p = .36). Following MUF, the CUF + MUF group had higher hematocrit (44.7 ± 0.50 g/dl) compared to the only CUF group (37.2 ± 0.49 g/dl), p ≤ .001 after adjusting for baseline hematocrit. Central venous pressure (mmHg) immediately following sternal closure was 9.27 ± 3.12 mmHg in the CUF + MUF group and 10.52 ± 2.2 mmHg in the only CUF group (p = .04). In the intensive care unit (ICU), they were 11.52 ± 2.20 mmHg in the only CUF group and 10.84 ± 2.78 mmHg in the CUF + MUF group (p = .02). Time to peripheral rewarming was 6.30 ± 3.91 h in the CUF + MUF group and 13.67 ± 3.91 h in the only CUF group (p = .06). Peak airway pressures in ICU were 17 ± 2 mmHg versus 20.55 ± 2.97 mmHg in CUF + MUF group & only CUF group, respectively, p < .001). Duration of mechanical ventilation was 6.3 ± 2.7 h in CUF + MUF group compared to 14.7 ± 3.5 h in the only CUF group (p = .002). IS was 11.52 ± 2.20 in the only CUF group compared to 10.84 ± 2.78 in CUF + MUFs group. Eight of 39 (20.5%) patients in the CUF + MUF group had IS > 10 compared to 22 of 40 (55%) patients in the only CUF group (p = .02). Serum Troponin-T and interleukin-6 levels were lower in the CUF + MUF group; TNF-α and CPK-MB were similar. ICU and hospital stay were similar. CONCLUSION: Patients undergoing a combination of CUF and MUF had higher postoperative hematocrit, decreased duration of mechanical ventilation, lower need for inotropes and lower interleukin-6 and Troponin-T levels. This group had better postoperative outcomes. This study was registered with the Clinical trials registry of India (CTRI/2017/11/010512) before commencement.

Efficacy of Single Low-Dose Rasburicase in Management of Tumor Lysis Syndrome in Leukemia and Lymphoma Patients.

BACKGROUND: Tumor lysis syndrome (TLS) is a metabolic emergency in hematology patients. The recommended dose of rasburicase for the management of TLS is 0.2 mg/kg per day for 5 days, which is cost prohibitive for many patients. We sought to determine the efficacy of single low-dose rasburicase in the prevention and treatment of hyperuricemia in TLS. PATIENTS AND METHODS: We planned a prospective study for the safety and efficacy of fixed (weight based) dose of rasburicase to manage TLS. Patients diagnosed with leukemia/lymphoma with laboratory or clinically confirmed TLS or presence of ≥ 2 high-risk factors and serum uric acid > 7.5 mg/dL were included. The primary endpoint was uric acid normalization (< 7.5 mg/dL) within 24 hours of rasburicase administration. RESULTS: Fifty-five patients were recruited for this study. Pediatric patients (< 18 years) accounted for 43.6% of cases. Rasburicase was provided prophylactically to 43 patients (78.2%) and for treating TLS to 12 (21.8%). Mean ± standard deviation serum uric acid at baseline and 24 hours was 9.2 ± 1.8 mg/dL and 3.2 ± 2.1 mg/dL, respectively. There was significant reduction in the serum uric acid and creatinine (P < .001) within 24 hours of rasburicase administration. The response was maintained up to 72 hours. A single dose of rasburicase was effective in 94.5% of patients. Single low-dose rasburicase led to 95% direct cost savings compared to the recommended dose. CONCLUSION: Single-dose rasburicase with frequent laboratory monitoring is effective in the management of TLS and offers significant cost reductions.

"Dial of a Clock" Search Pattern for Clinical Breast Examination.

BACKGROUND: Clinical breast examination (CBE) is an integral component of triple assessment for women presenting with symptomatic breast disease. Four common search patterns of CBE are "dial of a clock" (DC), "vertical strips" (VS), "quadrant-wise" (QW), and "concentric circles" (CC). The most sensitive search pattern of CBE has not been established. METHODS: A cross-sectional study was conducted on women with symptomatic breast disease, to measure various diagnostic performance indices of four different search patterns of CBE by a professor, a surgical resident trainee, and a trained nurse. Women were examined one at a time randomly by three examiners. Each examiner examined with four different search patterns of CBE, one method at a time. Any nodularity or lump detected was noted and the findings were compared with breast sonography, which was considered as the gold standard. Statistical analysis was done using STATA 14, SPSS 20, and OpenEpi software for diagnostic test indices. RESULTS: Sixty women (mean age = 39.6) with palpable findings of both breasts were included (n = 120). Most women presented with complaints of breast lump (70%) and mastalgia (27%). Sensitivity was highest for DC as elaborated [% (95% confidence interval)]: DC[73.2 (60-83)] > CC[66 (53-77)] > VS[62.5 (49-73)] > QW[58.9 (45-70)] for professor; DC[64.2 (51-75)] > VS[62.5 (49-73)] > CC[57.1 (44-69)] > QW[57.1 (44-69)] for resident; and DC[82.1 (70- 90)] > VS[78.5 (66-87)] > CC(75 (62-84)] > QW[73.2 (60-83)] for nurse. The minimum sonographic tumor size picked up by DC by all the examiners was 7 mm. CONCLUSIONS: The DC search pattern of CBE demonstrated the highest sensitivity for all the examiners. The trained nurse achieved the highest sensitivity among all the examiners.

Sestrin2 as Serum Protein Marker and Potential Therapeutic Target for Parkinson's Disease.

Sestrin2 (Sesn2) appears to mediate neuroprotection against Parkinson's disease (PD)-associated pathophysiology, however, the mechanism is unknown. This pilot study examines serum Sesn2 level in PD patients and older adult control and also interrogates the rescue effect of Syzygium aromaticum extract on the neurotoxicity by paraquat in neuroblastoma cells. The blood sample was collected from 36 PD patients and 54 older adult control and concentration of serum Sesn2 was measured by surface plasmon resonance and western blot. A significantly elevated level of Sesn2 (p < .0001) was observed in sera of PD group (15.96 ± 2.428 ng/µL) than the control (13.65 ± 2.125 ng/µL) which was further confirmed by western blotting. The receiver operating characteristic (ROC) curve (0.76) determined the threshold value of ≥14.58 ng/µL for differentiating PD from control. The S aromaticum extract exhibited the rescue effect from paraquat induced toxicity in SH-SY5Y cells. Further, these cells showed dose-dependent downregulation of p53, Sesn2, and phosphorylated-AMPK with concomitant increase in phosphorylated-p70S6K level than paraquat-treated cells. The differential level of Sesn2 in study subjects proposes its utility as one of the potential serum markers in PD. The ethanolic extract of S aromaticum may serve as a novel platform for management of PD-associated neurotoxicity.

Popliteal neurovascular bundle is safe during inside-out repair of medial meniscus without a safety incision.

PURPOSE: There is a theoretical risk of injury to neurovascular structures during inside-out meniscal repair without a safety incision, although there are limited studies assessing this risk. This simulation study on archival MRI films was performed to assess the risk for the popliteal neurovascular bundle and the peroneal nerve during passage of needles for inside-out meniscus repair without a "safety incision", thereby defining a "safe zone" of the menisci that can be safely repaired using this technique. METHODS: Archival MRI scans (n = 50) were retrieved and axial sections through the menisci were used for simulation. The needle passage was simulated for different points on the posterior horn and body of lateral and medial menisci at "half-hour" intervals using clock method (15° intervals) with three different portals and two different needle cannulas, resulting in six different scenarios of needle passage for each point on the meniscus. The distance of the needle in each scenario was measured from popliteal vessels (n = 50) and peroneal nerve (n = 10). The value "mean-3SD" was calculated for positive means and "Mean + 3SD" was calculated if the mean was negative. An additional 2 mm was defined as "safe distance". Thus, simulation models in which the mean - 3SD was less than 2 mm (or mean + 3SD was greater than - 2 mm for negative means) were labelled as "unsafe". RESULTS: Needle passage through medial meniscus at and medial to 1 o'clock position for a right knee (or 11 o'clock position for a left knee) was safe, irrespective of the portal and needle type. For the lateral meniscus, only the equatorial region was found to be safe with this method. CONCLUSIONS: The popliteal neurovascular bundle is safe during the inside-out medial meniscal repair without a safety incision. For the terminal-most part of the posterior horn, the AM portal and the straight cannula should be avoided. However, this method without safety incision cannot be recommended for lateral meniscus because of the risk to the popliteal vessels and the peroneal nerve. Instead, the inside-out method with a safety incision, or an all-inside method should be used for lateral meniscus. LEVEL OF EVIDENCE: III.

Serum creatinine and cystatin C-based index can be a screening biomarker for sarcopenia in older population.

PURPOSE: Considering the clinical impact of sarcopenia, it would be interesting to get a rapid and sensible screening tool. We conducted a cross-sectional study with the motive to use an index based on serum creatinine and cystatin C to screen sarcopenia in older people in outpatient settings. METHODS: 100 participants above the age of 65 years were recruited from the outpatient department of Geriatric medicine of a tertiary care hospital in India. Muscle mass, muscle strength and physical performance were measured by DXA scan, hand-held dynamometer and 4 m gait speed, respectively. Sarcopenia was identified using Asian working group of sarcopenia (AWGS) criteria. Serum creatinine and cystatin C were measured for all participants. Serum creatinine/cystatin C ratio and biochemical total body muscle mass index (TBMM) were calculated and its association was checked with sarcopenia. RESULTS: The prevalence of sarcopenia was 53%. Mean serum creatinine/cystatin C ratio was 74.79 ± 24.91. It was not significantly associated with sarcopenia. Mean biochemical TBMM index of participants was 36.40 ± 7.88 (males-38.77 ± 7.72, females-31.22 ± 5.13). The lower value of biochemical TBMM index was significantly associated with an increased risk of sarcopenia (p < 0.01). Cut-off value of 40.9 in males (sensitivity-79.41%; specificity-61.76%) and 32.2 in females (sensitivity-78.95%; specificity-66.67%) was proposed for identification of sarcopenia. CONCLUSION: Out of the two indices, only low biochemical total body muscle mass index is significantly associated with sarcopenia and a value of less than 40.9 in males and 32.2 in females can be used to screen sarcopenia in older people.

Optimal Angle of the Bone Tunnel for Avoiding Axillary Nerve Injuries During Arthroscopic Transosseous Rotator Cuff Repair: A Magnetic Resonance Imaging-Based Simulation Study.

BACKGROUND: Axillary nerve injury and suture cutout through the roof of the tunnel are potential complications of arthroscopic transosseous rotator cuff repair (ATORCR). PURPOSE: To determine a safe angle of drilling for the bone tunnel during ATORCR such that the axillary nerve is not at risk. The thickness of the bone bridge over the tunnel for different angles of drilling was also determined. STUDY DESIGN: Descriptive laboratory study. METHODS: The drilling of a straight tunnel was simulated on 30 magnetic resonance imaging (MRI) scans in the oblique coronal plane by drawing a straight line that passed at a "safe distance" of 5 mm from the axillary nerve and emerging at the medial border of the insertion of the rotator cuff on the greater tuberosity. The angle made by this line with the horizontal axis of the humerus was measured on 3 MRI sections: anterior (passing just posterior to the lateral lip of the bicipital groove), middle (at the most lateral point of the proximal humerus), and posterior (an equal number of cuts away from the middle section as between anterior and middle). The thickness of the overlying bone roof was measured for this line as well as for simulation lines drawn at 50°, 55°, 60°, and 65° with the horizontal axis. A "safe limit," defined as the mean - 2SD, was also calculated. RESULTS: The axillary nerve was found to be safe, with a safety margin of 5 mm, at drill angles of less than 61.1° and 60.3° in the posterior and middle sections, respectively. The safe limit value for thickness of the overlying bone roof for the tunnel drilled at 60° was 5.0 mm in the posterior section (mean, 8.2 ± 0.3 mm) and 5.5 mm in the middle section (mean, 8.1 ± 0.2 mm). In the anterior section, the minimum safe angle was 57.7°, and the mean thickness of the bone roof for the 55° angle was 6.3 ± 0.2 mm (safe limit, 3.7 mm). CONCLUSION: Straight bone tunnels in ATORCR surgery should be drilled at an angle of 60° to the horizontal axis of the humerus or 30° to the humeral shaft to ensure the safety of the axillary nerve while at the same time ensuring adequate thickness of the overlying bone roof. The anterior tunnel close to the bicipital groove should be drilled cautiously at 55° to the horizontal axis or 35° to the humeral shaft. CLINICAL RELEVANCE: The findings of the present study will help the surgeon choose the best angle for drilling tunnels during ATORCR surgery to avoid axillary nerve injuries as well as suture cut-through without the need for any proprietary device.

Prevalence, clinical & biochemical correlates of non-alcoholic fatty liver disease in overweight adolescents.

BACKGROUND & OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) characterized by excessive accumulation of fat in the liver, which can progress to inflammation, and cirrhosis, has emerged as an important complication of obesity in adults as well as children. This study was undertaken to assess the prevalence of NAFLD and its correlation with clinical and biochemical parameters in overweight Indian adolescents. METHODS: In this cross-sectional study, 218 overweight adolescents aged 10 to 16 yr and their parents were included. Measurements included anthropometry, ultrasonography to diagnose NAFLD, fasting glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lipids for adolescents and parents, and additional parameters of blood pressure, body fat percentage (BF%), fasting insulin, apolipoprotein C3, tumour necrosis factor-α and adiponectin for adolescents. The variables were compared between adolescents with and without NAFLD, and logistic regression analysis was performed. RESULTS: Mean age and body mass index (BMI)SD score (SDS) were 11.9±1.6 yr and 2.3±1.1, respectively. NAFLD was seen in 62.5 per cent of the adolescents. The prevalence of NAFLD in the parents was similar among the adolescents with and without NAFLD, while BMI and waist circumference SDS, BF per cent, blood pressure (BP), ALT, AST, insulin and homeostatic model assessment of insulin resistance (HOMA-IR) were significantly higher in the adolescents with NAFLD. On multiple logistic regression, abdominal obesity, HOMA-IR and BF per cent were independently associated with NAFLD with odds ratios (95% confidence interval) of 2.77 (1.40-5.47), 2.21 (1.16-4.21) and 2.17 (1.12-4.22), respectively. INTERPRETATION & CONCLUSIONS: NAFLD was noted among nearly two-thirds of the overweight adolescents. An independent association was observed between abdominal obesity, HOMA-IR and body fat percentage and NAFLD in overweight adolescents.

Comparison of intramyometrial vasopressin plus rectal misoprostol with intramyometrial vasopressin alone to decrease blood loss during laparoscopic myomectomy: Randomized clinical trial.

OBJECTIVE: To compare the efficacy and safety of intramyometrial vasopressin plus rectal misoprostol with intramyometrial vasopressin alone to reduce blood loss during laparoscopic myomectomy. STUDY DESIGN: A randomized, single-blind, controlled trial was conducted at All India Institute of Medical Sciences, New Delhi, India. Sixty women with symptomatic leiomyoma scheduled for laparoscopic myomectomy were recruited for the study. Thirty women received intramyometrial vasopressin plus rectal misoprostol (30 min before procedure) (Group I) and 30 women received intramyometrial vasopressin alone (Group II) during laparoscopic myomectomy. The primary outcome measure was intra-operative blood loss during surgery. Secondary outcome measures included decrease in postoperative haemoglobin, ease of enucleation of myomas, duration of surgery, need for additional haemostatic measures or blood transfusion, intra- and postoperative morbidity, and duration of hospital stay. RESULTS: The baseline demographic features and characteristics of leiomyomas were comparable in both groups. The mean (±standard deviation) blood loss in Group I was 139 ±â€¯96.7 ml, which was significantly less than that for Group II (206 ±â€¯101.2 ml) (p = 0.008). The mean postoperative haemoglobin was 11.6 ± 1.3 g/dl in Group I and 10.0 ± 1.2 g/dl in Group II (p = 0.001). Although blood loss was not clinically significant in either group, the decrease in haemoglobin was significantly higher in Group II. The mean score for ease of enucleation (surgeon-rated measure) was significantly lower in Group I (2.6 ± 1.1) compared with Group II (3.4 ± 1.1) (p = 0.029). Intra- and postoperative vital signs, duration of surgery, need for blood transfusion and postoperative morbidity were comparable in both groups. CONCLUSIONS: The addition of rectal misoprostol to intramyometrial vasopressin led to a significant reduction in blood loss and decreased the postoperative drop in haemoglobin. The combination also improved the ease of enucleation of myomas.