A Comparative Evaluation of the Efficiencies of Different Rotary File Systems in Terms of Remaining Dentin Thickness Using Cone Beam Computed Tomography: An In Vitro Study.

AIM: The aim of this study was to evaluate and compare the dentin thickness of the mesio-buccal canal of the lower first molar after canal preparation with three different rotary file systems using cone beam computed tomography (CBCT). METHODOLOGY: TruNatomy (Dentsply Sirona, USA), 2Shape (Micro-Mega, France), and One Curve (Micro-Mega, France) were the three different rotary files that were employed. A total of 45 excised human permanent first mandibular molars were divided into Groups A (TruNatomy), B (2Shape), and C (One Curve) at random. To measure the residual dentin thickness at 3 mm, 5 mm, and 7 mm from the radiographic apex, the mesial root of the tooth was removed from the tooth, and a mesio-buccal canal was taken. Samples were mounted in clear acrylic resin and were subjected to a pre-instrumentation CBCT scan. The mesio-buccal canal was cleaned and shaped while maintaining the final mesio-buccal canal preparation of Group A - 26/0.04, Group B - 25/0.04, and Group C - 25/0.04. The samples were extensively irrigated with 3% sodium hypochlorite and 17% EDTA, and a post-instrumentation scan was performed on them. Statistics were used to determine the values from CBCT scans that were recorded for pre- and post-instrumentations. RESULTS: The results showed that Group A had the greatest drop in dentin thickness, followed by Group B and Group C. The change in dentin thickness was greatest at 3 mm and 7 mm. CONCLUSION: In contrast to TruNatomy and 2Shape rotary file systems, One Curve has the advantage of maintaining a tooth's thickness at 3 and 7 millimeters from the radiological apex. Since the TruNatomy file system removes more dentin than the other two combined, it should be used cautiously. Choosing the right instrument is crucial for cleaning and shaping during root canal preparation.

Daratumumab for De-sensitization of Donor Specific Antibodies: Is it a Quicker and Easier way?

Antibodies directed against donor-specific HLA loci (DSA) has been proved as a main culprit for graft rejection, more specifically in HLA mismatched and haplo-identical transplant settings. There is no standardized regimen to manage the presence of DSAs in allogeneic stem cell transplantations (allo-SCTs). Most widely regimen includes combination of rituximab (anti CD20 antibody), Immunoglobulin (IVIG), plasma exchange, and buffy coat infusion, which is costly and time-consuming. Daratumumab (anti CD38 monoclonal antibody) is an effective therapeutic agent to deplete plasma cells and hence, it has a potential to reduce DSA. It has been utilized widely in solid organ transplantation for this purpose. We used this agent in two haplo-identical transplant patients to eliminate or reduce DSA. We observed definite either reduction or elimination in DSA levels in these cases and we could perform haplo-identical transplantation without much delay and with successful primary engraftment in both scenarios. We emphasize that literature on real-world utilization of daratumumab in allo-SCTs is limited. However, it has been utilized widely in solid organ transplantation for this purpose. Our experience with daratumumab regarding effective reduction of DSA followed by successful engraftment might encourage its use in de-sensitization protocols without much delay in transplantation.

The Other Infodemic: Media Misinformation about Involuntary Commitment for Substance Use.

BACKGROUND: As drug-related deaths have surged, the number and scope of legal mechanisms authorizing involuntary commitment for substance use have expanded. Media coverage of involuntary commitment routinely ignores documented health and ethical concerns. Prevalence and dynamics of misinformation about involuntary commitment for substance use have not been assessed. METHODS: Media content mentioning involuntary commitment for substance use published between January 2015 and October 2020 was aggregated using MediaCloud. Articles were redundantly coded for viewpoints presented, substances mentioned, discussion of incarceration, and mentions of specific drugs. In addition, we tracked Facebook shares of coded content. RESULTS: Nearly half (48%) of articles unequivocally endorsed involuntary commitment, 30% presented a mixed viewpoint, and 22% endorsed a health-based or rights-based critique. Only 7% of articles included perspectives of people with lived experience of involuntary commitment. Critical articles received nearly twice as many Facebook shares (199,909 shares) as supportive and mixed narratives combined (112,429 shares combined). DISCUSSION: Empirical and ethical concerns about involuntary commitment for substance use are largely absent from coverage in mainstream media, as are voices of those with lived experience. Better alignment between news coverage and science is vital to inform effective policy responses to emerging public health challenges.

Omega-3 fatty acids supplements for dry eye - Are they effective or ineffective?

Purpose: To evaluate effectiveness of omega-3 fatty acid supplements in relieving dry eye symptoms and signs in symptomatic visual display terminal users (VDT). Methods: A randomized controlled study was done; eyes of 470 VDT users were randomized to receive four capsules twice daily for 6 months (O3FAgroup), each containing 180 mg of eicosapentaenoic acid and 120 mg docosahexaenoic acid. The O3FA group was compared with another group (n = 480) who received four capsules of a placebo (olive oil) twice daily. Patients were evaluated at baseline, 1, 3, and 6 months, respectively. The primary outcome was improvement in omega-3 index (a measure of EPA and DHA ratio in RBC membrane). Secondary outcomes were improvement dry eye symptoms, Nelson grade on conjunctival impression cytology, Schirmer test values, tear film breakup time (TBUT), and tear film osmolarity. Means of groups (pre-treatment, 1, 3, and 6-months) were compared with repeated measure analysis of variance. Results: At baseline, 81% patients had low omega-3 index. In the O3FA group, a significant increase in omega-3 index, improvement in symptoms, reduction in tear film osmolarity, and increase in Schirmer, TBUT, and goblet cell density was observed. These changes were not significant in the placebo group. Improvement in test parameters was significantly (P < 0.001) better in patients with low omega3 index (<4%) subgroup. Conclusion: Dietary omega-3 fatty acids are effective for dry eye in VDT users; omega-3 index appears to be the predictor to identify potential dry eye patients who are likely to benefit from oral omega-3 dietary intervention.

Awareness Regarding Eye Donation among Doctors, Students, and Paramedics at a Tertiary Care Teaching Hospital.

INTRODUCTION: In the sub-continent, there is a huge discrepancy between the cornea collected and the ever-increasing demand. Lack of awareness, faulty perceptions, and unwillingness to donate corneas are the major hurdles. OBJECTIVES: To assess the level of awareness among doctors, students, and paramedics in a teaching hospital. MATERIALS AND METHODS: An analytical cross-sectional, pre-tested, study design assessed the awareness, knowledge, and attitude among health care workers (medical students, nurses, doctors, and paramedics) in the context of eye donation through a administered self-administered semi-structured questionnaire. RESULTS: In our study, 692 (57.7%) of the respondents were aware that the ideal time for donation was within six hours of death. Our study revealed that 875 (72.9) of the respondents were willing to donate their eyes; out of these 305 (25.4%) were MBBS students and 223 (18.6%) were nursing students, (Chi-square tests, p <0.001). Six-hundred and twenty-five (52.1%) respondents knew that the nearest eye bank should be contacted if they or any of their family members wished to donate their eyes. However, only 90 (7.5%) of the respondents' family/ relatives had donated his/her eyes. A significant association between knowledge of eye donation and the age, gender, religion, or marital status and knowledge of eye donation of participants was observed. CONCLUSION: The study highlights the need for creating awareness about eye donation among doctors, medical students, and paramedics, who can be an effective channel for planning, educating, and motivating the public to pledge for eye donation.

The Discriminatory Ability of Ganglion Cell Inner Plexiform Layer Complex Thickness in Patients with Preperimetric Glaucoma.

Purpose: To evaluate diagnostic performance of ganglion cell inner plexiform layer (GCIPL) and retinal nerve fiber layer (RNFL) parameters measured with Cirrus high-definition optical coherence tomography (OCT) in patients with preperimetric glaucoma. Methods: In this multicenter cross-sectional study, 150 eyes of 83 patients with preperimetric glaucoma were compared with 200 eyes of age and sex matched healthy subjects. All patients had visual field testing and OCT scanning of GCIPL and RNFL in all quadrants. The independent Samples t-test was used to determine if a difference exists between the means of two independent groups on a continuous dependent variable. The area under the receiver operating characteristic (ROC) curve (AUC) of each parameter was calculated for discriminatory ability between normal controls and preperimetric glaucoma. The sensitivity and specificity were estimated by point coordinates on ROC curve. Results: The best parameters for distinguishing preperimetric glaucoma from healthy eyes were the combined average GCIPL + average RNFL, followed by average RNFL + GCIPL (inferotemporal), and average RNFL + GCIPL (minimum). The GCIPL parameters with the highest to lowest AUC (in decreasing order) were inferotemporal, followed by average, minimum, superior, inferior, superonasal, inferonasal, superotemporal, and quadrants. The RNFL parameters with the highest to lowest AUC (in decreasing order) were average, followed by nasal, temporal, superior, and inferior quadrants. The sensitivity of combined GCIPL + RNFL parameters ranged 85%-88% and the specificity ranged 76%-88%. The sensitivity for RNFL parameters ranged 80%-90% and the specificity ranged 64%-88%. Conclusion: GCIPL and RNFL have good discriminatory ability; the sensitivity and specificity increase when both parameters are combined for early detection of glaucoma.

Long-term outcomes of small-incision cataract surgery in patients with uveitis.

Purpose: To evaluate the long-term outcomes of manual small-incision cataract surgery (MSICS) in eyes with uveitis. Methods: Patients who underwent MSICS for uveitic cataract from 2009 to 2019 were retrospectively evaluated. Visually significant cataract and presence of less than five cells per high-power field in the anterior chamber for a minimum of 3 months were the prerequisites for surgery. Patients with follow-up less than 9 months were excluded. Results: After exclusion, 283 eyes of 264 patients were evaluated. The mean age of patients was 44.3 ± 11.3 years. The mean follow-up duration was 22 ± 11.5 months. The mean surgical time was 11.2 ± 3.2 min. One hundred and seventy-two eyes (60.8%) had anterior uveitis, 78 (27.5%) had posterior uveitis, and 33 (11.7%) had panuveitis. At the final follow-up, 253 eyes (88.4%) had corrected distance visual acuity (CDVA) better than 0.6 log of minimum angle of resolution (LogMAR) unit. The final endothelial cell counts were significantly (analysis of variance [ANOVA], P = 0.001) lower in eyes with human leukocyte antigen (HLA)-B27-associated uveitis and in eyes with idiopathic anterior uveitis. Patients on systemic corticosteroids had significantly better (P = 0.031) final visual acuity than those without preoperative corticosteroids. Recurrent uveitis (43.8%), Posterior capsule opacification (PCO) (19.4%), glaucoma (8.5%), cystoid macular edema (CME; 13.5%), and Epiretinal membrane (ERM) (5.6%) were the frequent complications. A significantly worse (ANOVA, P = 0.001) visual prognosis was seen in patients with Vogt-Koyanagi-Harada disease (VKH), sarcoidosis, acute posterior multifocal placoid pigment epitheliopathy (APMPPE), and serpiginous choroiditis. Conclusion: MSICS is safe in most cataracts due to uveitis and results in improvement in CDVA at 9 months. Posterior capsule opacification, macular edema, persistent uveitis, etiology of uveitis, and use of preoperative steroids significantly influenced the visual outcome.

Safety and efficacy of cyclosporine (0.05% versus 0.09%) in dry eye disease. Is it the strength of cyclosporin that really matters?

INTRODUCTION: This is a multicenter, randomized, interventional, double masked study aimed to compare safety and efficacy of cyclosporine (0.05% versus 0.09%) in dry eye disease. MATERIALS AND METHODS: Random allocation of patients (n=450) was done in two groups by parallel assignment (1:1). Group1(n=225) received CAs 0.05% drops twice daily, and group 2 (n=225) received CAs 0.09% drops twice daily for 3 months. Primary outcomes were changes from baseline in Lissamine green staining score, Nelson grade on conjunctival impression cytology and tear film osmolarity. Secondary outcomes were changes in dry eye symptom score. Schirmer's test scores, changes in corneal fluorescein staining and changes in tear film break up time. RESULTS: Within the groups, there was a significant improvement (ANOVA, P<0.05) in tear film osmolarity, lissamine green staining score, dry eye symptom score, corneal fluorescein staining and Schirmer test scores over 3 months of intervention. However, the difference in Nelson Grade, goblet cell density, and tear film break-up time was not statistically significant. Between the groups, there was a significantly better improvement in tear film osmolarity (ANOVA, P<0.001), Lissamine green staining score (ANOVA, P=0.002), corneal fluorescein staining (ANOVA, P=0.011), dry eye symptoms (ANOVA, P=0.040) and Schirmer test scores (ANOVA, P=0.001) with CAs 0.09%. However, the improvement in Nelson grade, tear film break-up time was not significantly different between the two groups. The overall patient's comfort was significantly better over time in patients on CAs 0.05% (ANOVA, P<0.001). CONCLUSION: Increasing strength of CAs better improves corneal staining, tear production, tear film osmolarity but not conjunctival morphology and tear film stability.

Outcomes of COVID-19 in Hematopoietic Stem Cell Transplant Recipients: Multicenter Retrospective Analysis.

COVID-19, caused by the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), was declared a pandemic by the World Health Organization on March 9, 2020. Hematopoietic stem-cell transplantation (HSCT) recipients may be highly susceptible to infection and related pulmonary complications due to nascent immune systems or organ damage from treatment-related toxicities. Poor outcomes in such group of patients were linked to older age, steroid therapy at the time of COVID-19 infection, and COVID-19 infection within a year of HSCT. We studied a cohort of 28 hematopoietic stem cell transplant recipients (male 17, M:F ratio of 1.5) with COVID-19 infection from 1st June 2020, through 31st December 2020 for outcome. Fever was the most common symptom at the time of presentation in 22 (78.5%) patients. Mortality rate at Day 28 and Day 42 was found to be 4/28 (14.3%) and 7/28 (25%) respectively. Patients within one year of HSCT and severe infection had higher day 28 mortality (with p values = 0.038)". There was no relation of mortality with type of transplant.

Encouraging Outcomes of Alternate Donor Hematopoietic Stem Cell Transplant in Pediatric High-risk/Relapsed Leukemias: A Single Center Experience.

Outcomes of high-risk and relapsed pediatric acute leukemias continue to be suboptimal. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative modality. However, <30% of patients have matched sibling donors available. Hence, alternate donors (matched unrelated and haploidentical) are being used to improve outcomes. We retrospectively analyzed our data of all children with high-risk/relapsed acute leukemias who underwent alternate donor HSCT at our center from April 2015 to July 2020. A total of 15 patients were included-3 underwent matched unrelated and 12 underwent haploidentical HSCT. Before HSCT, all patients were in complete remission (CR): CR1-1, CR2-11, and CR3-3. All patients engrafted except one. Median time to neutrophil and platelet engraftment was 15 and 16 days, respectively. There were 3 transplant related mortalities. One patient was lost to follow-up. Remaining 11 patients remain in remission and are alive. The cumulative incidence of acute graft versus host disease was 57.1% and of chronic graft versus host disease was 21.4%. Overall survival was 80% and the event-free survival was 73.3%. The median follow-up of alive patients was 775 days (range: 333 to 2077 d). Our experience shows encouraging outcomes using alternate donor HSCT for these patients from developing world.

Convalescent plasma therapy for severe Covid-19 in patients with hematological malignancies.

BACKGROUND: Data on convalescent plasma therapy (CPT) in patients of hematological malignancies with severe Covid-19 is scarce. OBJECTIVE: To study 14-day mortality in patients who received CPT. PATIENTS & METHODS: Retrospective multicentre observational study conducted in 4 centres treating haematological malignancies across Delhi-national capital region. Total 33 haematological malignancies patients with severe Covid-19 who received CPT were analysed. RESULTS: The median age of the study cohort was 62 years (18-80 years). Twenty one percent patients had 1 comorbidity, 18 % had 2 comorbidities and 6% patients had 3 and 5 comorbidities each. Twenty four patients were on active therapy. Sixty nine percent of patients required ICU stay. Twenty five patients received plasma therapy within 7 days (early) of diagnosis of Covid-19 infection. Median day of plasma infusion from date of diagnosis of Covid-19 infection was 4 days (range: 2-25 days). Patient who had early initiation of plasma therapy had shorter duration of hospitalisation (12.7 vs 24.3 days, p = 0.000). Overall mortality in the cohort was 45.5%. There was no effect of disease status, active therapy, presence of comorbidity on mortality. There was no difference in the mortality in patients receiving early vs late initiation of plasma therapy or in patients receiving one versus two plasma therapy. CONCLUSIONS: We provide a large series of patients with hematological malignancies and role of CPT in this group.

Effect of age, comorbidity and remission status on outcome of COVID-19 in patients with hematological malignancies.

BACKGROUND: There is scarcity of data on outcome of COVID-19 in patients with hematological malignancies. Primary objective of study was to analyse the 14-day and 28-day mortality. Secondary objectives were to correlate age, comorbidities and remission status with outcome. METHODS: Retrospective multicentre observational study conducted in 11 centres across India. Total 130 patients with hematological malignancies and COVID-19 were enrolled. RESULTS: Fever and cough were commonest presentation. Eleven percent patients were incidentally detected. Median age of our cohort was 49.5 years. Most of our patients had a lymphoid malignancy (n = 91). One-half patients (52%) had mild infection, while moderate and severe infections contributed to one-fourth each. Sixty seven patients (52%) needed oxygen For treatment of COVID-19 infection, half(n = 66) received antivirals. Median time to RT-PCR COVID-19 negativity was 17 days (7-49 days). Nearly three-fourth (n = 95) of our patients were on anticancer treatment at time of infection, of which nearly two-third (n = 59;64%) had a delay in chemotherapy. Overall, 20% (n = 26) patients succumbed. 14-day survival and 28-day survival for whole cohort was 85.4% and 80%, respectively. One patient succumbed outside the study period on day 39. Importantly, death rate at 1 month was 50% and 60% in relapse/refractory and severe disease cohorts, respectively. Elderly patients(age ≥ 60) (p = 0.009), and severe COVID-19 infection (p = 0.000) had a poor 14-day survival. The 28-day survival was significantly better for patients in remission (p = 0.04), non-severe infection (p = 0.00), and age < 60 years (p = 0.05). CONCLUSIONS: Elderly patients with hematological malignancy and severe covid-19 have worst outcomes specially when disease is not in remission.

Allogeneic Hematopoietic Stem Cell Transplant Offer Good Outcomes in Pediatric Aplastic Anemia: Experience From Developing World.

Between 2014 and 2020, 31 patients with severe aplastic anemia (SAA) underwent full match allogeneic hematopoietic stem cell transplantation at our center. Of the 31 patients with SAA, 19 had acquired aplastic anemia, 2 had Diamond Blackfan anemia and 10 had Fanconi anemia. Donors were either matched sibling (n=29), related donors (n=2), or unrelated donors (n=3). Peripheral blood stem cells were the graft source in all the cases except 1. Fludarabine-based reduced intensity conditioning was used in all except for patients with a diagnosis of Diamond Blackfan anemia. All patients except 1 achieved hematologic recovery in the form of neutrophil engraftment at 13 days (range, 9 to 17), whereas platelet engraftment occurred at 14 days (range, 10 to 18). Graft versus host disease (GvHD) prophylaxis consisted of cyclosporine and methotrexate ±antithymocyte globulin (horse/rabbit). Acute GvHD developed in 12.9% patients, whereas no patients developed chronic GvHD till the time of last follow-up. The 2-year overall survival for the entire cohort was 93.21±4.6%. In patients with SAA, allogeneic stem cell transplant using fludarabine-based conditioning regimens are very well tolerated and have excellent outcomes in a full match setting.

Haploidentical Stem Cell Transplant With Post-transplant Cyclophosphamide for Chediak-Higashi Syndrome: A Very Rare Case Report.

Chediak-Higashi syndrome is a rare immunodeficiency disorder for which hematopoietic stem cell transplant (HSCT) is the only curative treatment option. HSCT only corrects the hematologic and immunologic manifestations of the disease but neurologic complications may still progress after transplant. Haploidentical HSCT (haplo-HSCT) has evolved as a feasible alternative for patients with primary immunodeficiency. More recently, there has been use of haplo-HSCT with post-transplant cyclophosphamide. However, only 4 cases of Chediak-Higashi syndrome have been reported using this approach. Here, the authors describe a case of a 17-month-old boy who was successfully treated by haplo-HSCT with reduced-toxicity conditioning (fludarabine/treosulfan/melphalan) and post-transplant cyclophosphamide.

Autologous stem cell transplant in adult multiple sclerosis patients: A study from North India.

INTRODUCTION: Autologous Stem Cell Transplant (ASCT) provides long periods of progression-free-survival in multiple sclerosis (MS). This is an observational study to demonstrate the safety of ASCT in MS patients at a transplant center in North India using a lymphoablative regimen. MATERIALS AND METHODS: MS patients > 18 years referred by a neurologist or who came of their own volition were evaluated. Kurtzke Expanded Disability Status Scale (EDSS) score was calculated and those with a score of >7 were excluded. Informed written consent was taken. Mobilization was done with G-CSF with prednisolone to prevent disease flare-up. A minimum of 2 × 106 CD34 cells/kg was collected. Conditioning regimen consisted of rabbit ATG and cyclophosphamide. Rituximab 375 mg/m2 was given to prevent EBV reactivation and disease relapse. Antibiotic prophylaxis was given with levofloxacin, fluconazole, and valacyclovir. Any persistent change in EDSS scores ≥0.5 was considered significant. RESULTS: Twenty patients were included. Seven patients had positive urine cultures prior to transplant and were treated before starting any chemotherapy. Majority patients were women (13/20). All patients developed febrile neutropenia, which was managed as per department policy. There was no mortality. Subjective symptoms improved in all patients. EDSS score improved in 6/19 patients (5/6 with RRMS) with no disease progression in any patient at a median follow-up duration of 242 days. CONCLUSION: ASCT can be done safely for patients with relatively high EDSS scores with additional precautions for screening for infections. RRMS patients with the active disease show most improvement. SPMS patients may not show significant improvement in the short term.

Azacytidine in Newly Diagnosed FLT3-ITD-Positive Acute Myeloid Leukemia Presenting with Pneumonia: A Case Series.

Acute myeloid leukemia (AML) is an aggressive disease that predisposes the patients to infections. FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) positive AML is a type of high-risk AML. Pneumonia is a common complication in patients of AML both due to the disease itself and as a result of induction chemotherapy. Treating AML patients who present with pneumonia is a challenge as induction chemotherapy further increases the severity and mortality of pneumonia as it causes myelosuppression. We report four patients with newly diagnosed FLT3-ITD-positive AML who had pneumonia at presentation. All four cases required induction chemotherapy with 7+3 which could not be given due to their poor general condition, secondary to pneumonia. Therefore, they were given low-intensity therapy, in the form of azacytidine, to prevent further progression of AML while they were recovering from pneumonia and became well enough to tolerate intensive induction chemotherapy. This treatment strategy of using a bridge before intensive chemotherapy was successful in our patients and 3 out 4 achieved documented remission. In our opinion, patients with newly diagnosed FLT3 positive AML with pneumonia can be given low-intensity chemotherapy such as azacytidine until the remission of pneumonia for better patient outcomes.