Wiskott-Aldrich syndrome protein expression in female WAS carriers: A flow cytometry study from North India.

INTRODUCTION: Wiskott-Aldrich syndrome (WAS) is a rare X-linked inborn error of immunity characterized by microthrombocytopenia, infections, eczema, and increased predisposition to develop autoimmunity and malignancy. Flow cytometric assay for determining WAS protein (WASp) is a rapid and cost-effective tool for detecting patients. However, very few studies described WASp expression in female carriers. Most WAS carriers are clinically asymptomatic. Active screening of female family members helps identify female carriers, distinguish de novo mutations, and to select appropriate donor prior to curative stem cell transplantation. This study was undertaken to evaluate the diagnostic capability of flow cytometry-based WASp expression in peripheral blood cells to identify carriers and compare WASp expression in different blood cell lineages. PATIENTS AND METHODS: Female patients, heterozygous for WAS gene, were enrolled in this study conducted at Pediatric Allergy Immunology Unit, Advanced Pediatric Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India. Flow cytometric assessment of WASp expression in lymphocytes, monocytes, and neutrophils was carried out and compared with healthy control and affected patients. The results were expressed in delta (Δ) median fluorescence intensity (MFI) as well as stain index (SI), which is the ratio of ΔMFI of patient and ΔMFI of control. RESULTS: Thirteen mothers and two sisters of genetically confirmed WAS patients were enrolled in the study. All enrolled females were clinically asymptomatic and did not have microthrombocytopenia. Low WASp expression (SI < 1) was seen in lymphocytes and monocytes in 10 (66.6%) carriers. Females with variants in proximal exons (exons 1 and 2) were found to have lesser expression than those with distal (exons 3-12) variants. CONCLUSION: Flow cytometry is a rapid, easily available, cost-effective tool for WASp estimation. Lymphocytes followed by monocytes are the best cell lineages for WASp estimation in carrier females. However, genetic testing remains the gold standard, as carrier females with variants in distal exons may have normal WASp expression.

X-Linked Lymphoproliferative Syndrome: A Spectrum of Clinical and Immunological Profile and Novel Pathogenic Variants from Chandigarh, India.

INTRODUCTION: X-linked lymphoproliferative syndrome (XLP) is a rare primary immune deficiency. Two types of XLP have been described: XLP-1 and XLP-2. METHODS: We found 7 patients with XLP (3 had XLP-1 and 4 had XLP-2) after reviewing the data from Pediatric Immunodeficiency Clinic from 1997 to 2021. RESULTS: Mean age at diagnosis was 3.8 years, and mean delay in diagnosis was 2.6 years. Five patients had recurrent episodes of infections. Four patients developed at least one episode of hemophagocytic lymphohistiocytosis (HLH) (2 with XLP-1 and 2 with XLP-2). Of these, 2 had recurrent HLH (both with XLP-2). Epstein-Barr virus (EBV) infection was detected in 2 (1 with XLP-1 and 1 with XLP-2). Both these patients had HLH. One child with XLP-2 had inflammatory bowel disease. Hypogammaglobulinemia was seen in 3 (2 with XLP-1 and 1 with XLP-2). Genetic analysis showed previously reported variants in 5, while 2 had novel variants (one in exon 7 of XIAP gene [c.1370dup p.Asn457Lysfs Ter16] and other had splice site variant in intron 1 of SH2D1A gene [c.138-2_138-1insG]). Episodes of HLH were managed with intravenous immunoglobulin (IVIg), methylprednisolone, oral prednisolone, cyclosporine, and rituximab. Inflammatory bowel disease was managed using oral prednisolone and azathioprine. One patient underwent haploidentical hematopoietic stem cell transplantation. One child with XLP-2 and WAS died because of fulminant pneumonia. DISCUSSION/CONCLUSIONS: XLP should be considered as a strong possibility in any patient with features of HLH, repeated infections with hypogammaglobulinemia, persistent EBV infection, and early-onset IBD.

Optochiasmatic Cavernomas: Updated systematic review and proposal of a novel classification with surgical approaches.

Cavernomas are histologically benign vascular malformations found at different sites in the brain. A rare site for such cavernomas, however, is the anterior optic pathway, comprising the optic nerve, chiasma, and optic tract-called optochiasmatic cavernomas (OCC). These lesions usually present with sudden onset or progressive vision loss, headache, and features mimicking pituitary apoplexy. In this paper, we describe a case of OCC operated at our center. We carry out an updated review of literature depicting cases of OCC, their clinical presentation, management, and postoperative complications. We also propose a novel classification system based on lesion location and further analyze these cavernoma types with respect to the surgical approach used and visual outcome. A 30-year-old lady had presented with a 3-week history of progressive bilateral vision loss and headache. Based on imaging, she was suspected to have a cavernous angioma of the chiasma and left optic tract. Due to progressive vision deterioration, the lesion was surgically excised using pterional craniotomy. Postoperatively, her visual symptoms improved, but she developed diabetes insipidus. Clinical and radiological follow-up has been done for 18 months after surgery. A total of 81 cases have been described in the literature, including the present case. Chiasmal apoplexy is the most common presentation. Surgical excision is the standard of care. Our analysis based on lesion location shows the most appropriate surgical approach to be used for each cavernoma type. Visual outcome correlates with the preoperative visual status. Visual outcome is good in patients presenting with acute chiasmal apoplexy, and when complete surgical excision is performed. The endonasal endoscopic approach was found to provide the best visual outcome. In addition to preoperative visual status, complete surgical excision predicts favorable visual outcomes in OCC. Our proposed classification system guides the appropriate surgical approach required for a particular location of the cavernoma.

Alignment efficiency and three-dimensional assessment of root resorption after alignment with conventional and copper-nickel-titanium archwires: A randomized controlled trial.

OBJECTIVE: To compare alignment efficiency and root resorption between nickel-titanium (NiTi) and copper-nickel-titanium (CuNiTi) archwires after complete alignment in mandibular anterior region. METHODS: In this two-arm parallel single-blind randomized controlled trial, forty-four patients with Class I malocclusion with mandibular anterior crowding were recruited form orthodontic clinic of All India Institute of Medical Sciences (Jodhpur, India). Patients were randomly allocated into NiTi and CuNiTi groups, with a 1:1 allocation. Alignment was performed using 0.014-in, 0.016-in, 0.018-in, 0.019x0.025-in archwire sequence in the respective groups, which terminated in 0.019 x 0.025-in stainless-steel working archwire. The primary outcome was alignment efficiency, measured on study models from baseline (T0) to the first, second, third, fourth and fifth-month (T5). Secondary outcome was root resorption, measured from CBCT scans taken at T0 and T5. Mixed-factorial ANOVA was used to compare Little's Irregularity Index (LII). For assessing the proportion of patients with complete alignment at the end of each month, Kaplan-Meier survival curve was built and time to treatment completion was compared between groups using log rank test. Paired t-test was used to assess external apical root resorption (EARR) within groups, whereas independent t-test was used to evaluate LII and EARR between the groups. RESULTS: Twenty-two patients were recruited in each group. One patient was lost to follow-up in the CuNiTi group. No statistically significant differences were observed in alignment efficiency between the groups (p>0.05). Intergroup comparison revealed that the changes in root measurement in three-dimensions were not statistically significant (p>0.05), except for mandibular right central incisor, which showed increased resorption at root apex in NiTi group (p<0.01). CONCLUSION: The two alignment archwires showed similar rate of alignment at all time points. Root resorption measurement did not differ between the NiTi and CuNiTi groups, except for the mandibular right central incisor, which showed more resorption in NiTi group.

Electronic-PRO Measures for adverse events Of Treatment In ONcology (E-PROMOTION).

PURPOSE: Cancer patients struggle with the trauma of the disease and its treatment. PRO-CTCAE was developed to improve the recording of underreported symptomatic toxicities. We evaluated the improvement and ease in reporting symptomatic adverse events through add-on PRO-CTCAE (via a mobile application) compared to standard clinician-reported outcomes in routine clinical practice. We also evaluated changes in the health-related quality of life (HRQoL). METHODS: 110 cancer patients were studied for three weeks between their first and second chemotherapy session. HRQoL was assessed using EORTC QLQ-c30. RESULTS: Fifty-three patients self-reported their symptomatic adverse events on the day 7th & day 14th after the first cycle of chemotherapy. For the other fifty-seven patients, recording of adverse events was done by standard clinician-reported outcomes. All the patients in the study group reported adverse events compared to only 21 % in the standard reporting group. All 15 domains of adverse events were reported in the self-reporting group compared to only 5 in the standard reporting group. The self-reporting group had a significantly better overall quality of life. CONCLUSIONS: Self-reporting of adverse events using mobile app-based PRO-CTCAE helps patients and clinicians with better documentation of symptomatic toxicities of chemotherapy, reducing the burden on physicians and improving patient satisfaction. Mobile app-based self-reporting empowers cancer patients undergoing treatment, improves their quality of life, and should be implemented in routine clinical practice. Wider implementation can lead to further optimised solutions.

Clinical, immunological and molecular profiles of DOCK8 deficiency in six patients from a tertiary care centre in North India.

BACKGROUND: Dedicator of cytokinesis protein 8 (DOCK8) deficiency is an autosomal recessive form of combined immunodeficiency. This rare disorder is characterized by an increased predisposition to allergy, autoimmunity and malignancies. OBJECTIVES: To analyse clinical, immunological and molecular profiles of patients with DOCK8 deficiency. METHODS: Clinic records of all patients attending the primary immunodeficiency clinic from 2018 to 2021 were reviewed. Six patients from five families were found to have DOCK8 deficiency. RESULTS: Median age at diagnosis was 7.5 years (range 2-13), with a male/female ratio of 5 : 1. Among the six patients, recurrent eczematous skin lesions were the predominant cutaneous manifestation, present in five patients (83%). Warts and molluscum contagiosum were evident in two patients (33%) and one patient (16%), respectively. Two patients had recalcitrant prurigo nodularis lesions and two had epidermodysplasia verruciformis-like lesions. Food allergies and asthma were reported by one patient each. Of the six patients, recurrent sinopulmonary infections were detected in five (83%). Epstein-Barr virus-driven non-Hodgkin lymphoma with liver metastases was the only case of malignancy, in a 4-year-old boy. IgE was elevated in all patients. Lymphopenia and eosinophilia were observed in three patients (50%) and five patients (83.3%), respectively. Genetic analysis showed DOCK8 pathogenic variants in all patients: homozygous deletion mutations in two patients, compound heterozygous deletion mutations in one, and homozygous nonsense mutations in two. A novel pathogenic homozygous missense variant in the DOCK8 gene was identified in one patient. CONCLUSIONS: DOCK8 deficiency should be considered as a possibility in any patient with early onset eczema, cutaneous viral infections and increased predisposition to allergy, autoimmunity and malignancy.

Systematic review analyzing significance of endometrial cavity fluid during assisted reproductive techniques.

OBJECTIVE: The objective of our study is to estimate the prevalence of endometrial cavity fluid (ECF) in Assisted Reproductive Techniques (ART) cycles and analyze its effects on pregnancy outcome in such cycles. DATA SOURCES: PubMed, Cochrane Central, Scopus, and clinicaltrials.gov were searched for articles. The reference lists of relevant publications were explored for other studies. STUDY ELIGIBILITY CRITERIA: Studies that had assessed the pregnancy outcome in ART cycles and had commented on ECF accumulation were included. Pregnancy outcomes were assessed in all ART cycles where ECF was observed and were compared to the non-ECF cycles. RESULTS: A total of nine studies were included in the meta-analysis for a total of 28,210 cycles. Pooled analysis of the prevalence of ECF cycles out of total cycles in females undergoing ART using a fixed effect model showed that it was 14% (95% CI is 13% to 14%; I2 = 99%, p = < 0.01). The random effect model prevalence of ECF cycles was around 7% (95% CI: 4% to 10%). There was a statistically significant (25%) decrease in pregnancy rates per cycle transfer in the ECF cycle versus the non-ECF cycle group during ART [OR = 0.75, 95% CI = 0.67-0.84), p < 0.001; moderate quality evidence]. When ECF size was compared, there was a statistically significant increase in pregnancy rates if ECF size was less than 3.5 mm versus greater than or equal to 3.5 mm [OR = 13.67, 95% CI = 1.43-130.40), p = 0.02; high quality evidence]. Sub-group analysis revealed that the ECF present at the time of embryo transfer significantly decreased the pregnancy rates by 26% as compared to the group where the ECF was not present at the time of embryo transfer [OR = 0.74, 95% CI = 0.65-0.85), p < 0.001]. CONCLUSIONS: This meta-analysis proposes that the presence of ECF significantly decreases the implantation and pregnancy rates of ART cycles, and even more so if its size is greater than 3.5 mm. Interventions to decrease ECF formation or treat it have enhanced the pregnancy outcome in ART cycles. PROSPERO REGISTRATION: Date: 17th September 2020; Number: CRD42020182262.

Safety and Efficacy of Resveratrol in Healing of Maxillofacial Fractures: A Randomized Controlled Study.

Objectives: To assess the efficacy of resveratrol in improving functional outcomes following open reduction and internal fixation of maxillofacial fractures. Study Design: A single-center, randomized, parallel group, prospective, double-blind clinical trial was conducted on 40 patients between the age 20 and 60 years, requiring open reduction and internal fixation of maxillofacial fractures. The selected patients were randomly divided into two groups, Group 1 (placebo) and Group 2 (resveratrol) where tablets resveratrol 500 mg were given twice daily for 1 month following open reduction and internal fixation of fractured segments. Bite force was calculated pre-operatively and on the 1st, 4th, 8th and 12th week postoperatively. Serum markers osteocalcin and alkaline phosphate were calculated pre-operatively and at 4th and 12th week postoperatively. Results: Bite force (690.55 ± 262.00) in the resveratrol group was higher than the placebo group (553.27 ± 300.08) at 12th week postoperatively. However, the difference was non-significant statistically (p = 0.132). Resveratrol group (116.80 ± 55.25) showed better maintenance of serum ALP level as compared to placebo group (107.90 ± 42.99) at 12th week postoperatively, but again it lacked statistical significance (p = 0.573). Resveratrol group after initial reduction at 4th week showed serum osteocalcin levels nearly equal to the preoperative values at 12th week, while the placebo group showed a decline both at 4th and 12th week postoperatively. However, these results were not statistically significant (p = 0.065). Conclusion: There was no statistically significant difference in bite force, serum ALP level and serum osteocalcin levels between placebo group and resveratrol group. Though not statistically significant but early increased level of serum osteogenic markers, better restoration of bite force in group 2 (tab. Resveratrol) indicates toward its possible optimistic role in maxillofacial fracture healing. More studies with larger sample sizes are needed in order to confirm the efficacy of this drug in maxillofacial fracture.

Radiation dose analysis of computed tomography coronary angiography in Children with Kawasaki disease.

BACKGROUND: There is evolving role of computed tomography coronary angiography (CTCA) in non-invasive evaluation of coronary artery abnormalities in children with Kawasaki disease (KD). Despite this, there is lack of data on radiation dose in this group of children undergoing CTCA. AIM: To audit the radiation dose of CTCA in children with KD. METHODS: Study (December 2013-February 2018) was performed on dual source CT scanner using adaptive prospective electrocardiography-triggering. The dose length product (DLP in milligray-centimeters-mGy.cm) was recorded. Effective radiation dose (millisieverts-mSv) was calculated by applying appropriate age adjusted conversion factors as per recommendations of International Commission on Radiological Protection. Radiation dose was compared across the groups (0-1, 1-5, 5-10, and > 10 years). RESULTS: Eighty-five children (71 boys, 14 girls) with KD underwent CTCA. The median age was 5 years (range, 2 mo-11 years). Median DLP and effective dose was 21 mGy.cm, interquartile ranges (IQR) = 15 (13, 28) and 0.83 mSv, IQR = 0.33 (0.68, 1.01) respectively. Mean DLP increased significantly across the age groups. Mean effective dose in infants (0.63 mSv) was significantly lower than the other age groups (1-5 years 0.85 mSv, 5-10 years 1.04 mSv, and > 10 years 1.38 mSv) (P < 0.05). There was no significant difference in the effective dose between the other groups of children. All the CTCA studies were of diagnostic quality. No child required a repeat examination. CONCLUSION: CTCA is feasible with submillisievert radiation dose in most children with KD. Thus, CTCA has the potential to be an important adjunctive imaging modality in children with KD.

Tuberculosis and Bacillus Calmette-Guérin Disease in Patients with Chronic Granulomatous Disease: an Experience from a Tertiary Care Center in North India.

Chronic granulomatous disease (CGD) is a phagocytic defect characterized by recurrent bacterial and fungal infections. We report clinical profile of patients with CGD and mycobacterial infections in a cohort from North India. A review of clinical and laboratory records was carried out for patients with CGD registered at our center between 1990 and 2021. Of the 99 patients with CGD, 22 had mycobacterial infections-Mycobacterium tuberculosis and M. bovis-BCG in 11 each. Among the children with M. bovis-BCG infection, 6 had localized and 5 had disseminated BCG disease. Median age at onset of symptoms and diagnosis of BCG disease was 5 months and 15 months, respectively. While disseminated forms of BCG were noted only in CYBB defect, none of the patients with NCF1 defect developed complications due to BCG vaccine. A recurring radiological feature was left axillary lymph node calcification, which was present in around 50% of CGD patients with BCG infections. Of 11 patients with tuberculosis, pulmonary, pleuro-pulmonary, abdominal, and disseminated forms were present in 6, 1, 2, and 2, respectively. Median age at onset of symptoms and diagnosis of tuberculosis was 129 months and 130 months, respectively. Molecular defects were identified in CYBB (5), NCF1 (4), and CYBA (1). Incidence of tuberculosis and BCG-related complications in patients with CGD is higher than the normal population. Screening for CGD is warranted in any patient with adverse reactions to BCG vaccination, calcification of left axillary lymph node, and persistent, recurrent or disseminated forms of tuberculosis.

Occurrence of Kawasaki disease and neoplasms in temporal proximity-single-center experience and systematic review of literature.

Various factors (e.g., infections) have been postulated to trigger Kawasaki disease (KD) in genetically predisposed individuals. Whether neoplasms can trigger KD is largely unknown due to paucity of data. Herein, we provide a detailed account of KD occurring in temporal proximity (within 6 months) to neoplasms ('neoplasm-KD'). Patients with 'neoplasm-KD' diagnosed/treated at our center from January 1994 to May 2021 were included. Additionally, we performed a systematic literature review (as per PRISMA 2020 guidelines) utilizing PubMed, Web of Science and Scopus databases to retrieve details of all patients with 'neoplasm-KD' reported till June 2021. Patients with multisystem inflammatory syndrome in children were excluded. As all reports pertained to case description(s), risk of bias assessment was not performed. The details of patients with 'neoplasm-KD' were analyzed using SPSS software. Primary and secondary outcomes were occurrence of coronary artery abnormalities (CAAs) and clinical characteristics of 'neoplasm-KD', respectively. A total of 25 patients (data from 18 reports) were included in the 'neoplasm-KD' dataset. The most frequently diagnosed neoplasm was acute lymphoblastic leukemia followed by neuroblastoma and acute myeloblastic leukemia. Overall, CAAs were noted in 48% of patients. Interval between diagnoses of KD and neoplasm was shorter in patients with CAAs as compared to patients with normal coronary arteries (p-value = 0.03). Besides providing a comprehensive description of 'neoplasm-KD', this study raises a possibility that neoplasms might trigger KD. Also, 'neoplasm-KD' may be associated with a higher risk of development of CAAs. However, the small size of 'neoplasm-KD' dataset precludes definitive conclusions regarding this association. Funding: nil. Registration: PROSPERO (CRD42021270458).

This study is the first exhaustive description of cancers and Kawasaki disease (KD) occurring in close temporal proximity. Nearly half of these patients develop coronary artery abnormalities. In KD, persistent lymphadenopathy, enlargement of liver/spleen and development of low blood cell counts should trigger evaluation for cancer. Our study also raises a possibility that cancers might occasionally trigger KD.

Kawasaki Disease and Inborn Errors of Immunity: Exploring the Link and Implications.

The exact etiopathogenesis of Kawasaki disease (KD), the most common childhood vasculitis, remains unknown; however, an aberrant immune response, possibly triggered by an infectious or environmental agent in genetically predisposed children, is believed to be the underlying pathogenetic mechanism. Patients with inborn errors of immunity (IEI) are predisposed to infections that trigger immune dysregulation due to an imbalance in various arms of the immune system. KD may develop as a complication in both primary and secondary immunodeficiencies. KD may occur either at disease presentation or have a later onset in IEIs. These include X-linked agammaglobulinemia (XLA), selective IgA deficiency, transient hypogammaglobulinemia of infancy; Wiskott-Aldrich syndrome (WAS), hyper IgE syndrome (HIES); chronic granulomatous disease (CGD), innate and intrinsic immunity defects, and autoinflammatory diseases, including PFAPA. Hitherto, the association between KD and IEI is confined to specific case reports and case series and, thus, requires extensive research for a comprehensive understanding of the underlying pathophysiological mechanisms. IEIs may serve as excellent disease models that would open new insights into the disease pathogenesis of children affected with KD. The current review highlights this critical association between KD and IEI supported by published literature.

Impact of COVID-19 Pandemic on Clinical Care of Patients and Psychosocial Health of Affected Families with Chronic Granulomatous Disease: an Observational Study from North India.

Day-to-day clinical management of patients with inborn errors of immunity, including chronic granulomatous disease (CGD), has been affected by the coronavirus disease-2019 (COVID-19) pandemic. There is a dearth of information on impact of this pandemic on clinical care of children with CGD and psychological profile of the caretakers. Among the 101 patients with CGD followed up in our center, 5 children developed infection/complications associated with COVID-19. Four of these children had a mild clinical course, while 1 child developed features of multisystem inflammatory syndrome in children (MISC) requiring intravenous glucocorticoids. Parents and caretakers of CGD patients (n = 21) and 21 healthy adults with similar ages and genders were also evaluated on the following scales and questionnaires: COVID-19 Fear Scale (FCV 19S), Impact of Event Scale (IES-R), Depression, Anxiety, and Stress Scale (DASS 21), Preventive COVID-19 Behavior Scale (PCV 19BS), and a "COVID-19 Psychological wellbeing questionnaire." Median age of the parents/caregivers was 41.76 years (range: 28-60 years). Male:female ratio was 2:1. In the study group, 71.4% had higher IES scores compared to 14.3% in controls. The caregivers had a high prevalence of stress, anxiety, avoidance behavior, and depression compared to controls (p < 0.001). Children with CGD have had predominantly mild infection with COVID-19; however, caregivers/parents of these children were at risk of developing psychological distress. The COVID-19 pandemic has brought to light the importance of patients' and caretakers' mental health which needs periodic assessment and appropriate interventions.

Apremilast Add-On Benefits Over Conventional Drugs (ABCD) in Unstable Non-segmental Vitiligo: A 12-Week Single-Center Randomized Controlled Trial.

Background Apremilast is an oral phosphodiesterase-4 enzyme inhibitor that modulates the immune system by increasing intracellular cyclic adenosine monophosphate levels and inhibiting inflammatory cytokines synthesis. We aimed to compare the efficacy and safety of add-on apremilast in combination therapy with standard treatment in patients with unstable, non-segmental vitiligo. Methods The study was a 12-week randomized, controlled, parallel-group, open-labeled trial. The control group received standard treatment (n=15), and the intervention group received 30 mg apremilast twice daily in addition to standard treatment (n= 16). Time to the first sign of re-pigmentation, halt in progression, and change in vitiligo area scoring index (VASI) score is the primary outcomes. Normality was assessed, and appropriate parametric and nonparametric tests were undertaken. Results Thirty-seven participants were randomized into two groups, and analysis was done on thirty-one participants. Over the treatment duration of 12 weeks, the median time to observe the first sign of re-pigmentation was four weeks in the add-on apremilast group compared to seven weeks in the control group (p=0.018). The halt in progression was observed more in the add-on Apremilast group (93.75%) compared to the control group (66.66%) (p=0.08). The VASI score decreased by 1.24 in the add-on apremilast group and 0.05 in the control group (p= 0.754). Parameters including body surface area, dermatology life quality index, and body mass index reduced significantly, while the visual analog scale increased significantly in the add-on apremilast group. However, results were comparable between groups. Conclusions Treatment with add-on apremilast accelerated clinical improvement. It also reduced disease progression and improved the disease index among participants. However, add-on apremilast had a lower tolerability profile than the control group.

A prospective randomized controlled study of Mycobacterium Indicus Pranii vaccine, Measles Mumps Rubella vaccine and Vitamin D3 in extragenital cutaneous warts.

DESIGN: Interventional, prospective, four arm randomized control. SETTING: Outpatient department, Department of Dermatology, Venereology and Leprology, AIIMS Jodhpur (Rajasthan), India. PARTICIPANTS: Two hundred patients. METHODS: The intervention administered in the groups were normal saline (A), vitamin D3 (B), MIP (C), and MMR (D). The injections were given into the largest wart at 2-weekly intervals until complete clearance or for a maximum of seven sittings. Post-treatment clearance of the injected wart and the distant wart was compared on the basis of change in wart number, percentage clearance, and mean time to complete clearance. Side effects were recorded. RESULTS: A total of 197 patients were recruited. The mean percentage improvement in the injected and non-injected warts was 68.4% and 66.8%, respectively. Intention to treat analysis (ITT) showed that complete clearance of lesions in injected wart occurred in placebo, vit D3 , MMR, and MIP arms in 64%, 66%, 58%, and 55% patients, respectively (p > 0.05), while in the non-injected warts in 62%, 64%, 52%, and 53%, respectively (p > 0.05). The mean time to achieve complete clearance of wart was fastest in MIP at 7.1 weeks followed by MMR at 7.2 weeks, VIT D3 at 7.4 weeks and in placebo group 7.8 weeks (p > 0.05). Side effects noted were fever, pain, erythema, and swelling which was highest in VIT D3 group (p < 0.05). CONCLUSION: The efficacy of immunotherapies was comparable to placebo with minimal side effects.

The Clinical Efficacy of EMLA as a Topical Anesthetic Agent Instead of Palatal Injection During Maxillary Dental Extractions: A Randomized Controlled Trial.

Background: Even after the invention of the modern injection techniques, palatal injection still remains a painful experience for patients, and this pain is attributed to the presence of rich nerve complement and displacement of tightly adherent palatal mucosa during anesthesia. Aim: To check the clinical efficacy of EMLA as a topical anesthetic agent instead of palatal injection during maxillary dental extractions. Methodology: The trial includes a total of 102 participants, in whom maxillary molar extractions were indicated, were randomly divided into the experimental group (eutectic mixture of local anesthesia (EMLA) topical application was used along with buccal injection) and control group (palatal injection along with buccal injection). Pain perception during extraction was recorded using the visual analog scale (VAS). Results: Mean VAS score for 'injection' in control group patients was 5.2 ± 2.08 in contrast to no pain in experimental group. In experimental group, mean VAS score on 'probing' was 0.92 ± 1.50. VAS score on 'extraction' in EMLA group was little higher though the difference was not statistically significant. The overall experience using Liekert's scale was higher in experimental group (4.0 ± 0.76) as compared to (3.3 ± 0.82) in control group leading to higher overall satisfaction among patients who underwent extraction in the experimental group. Conclusion: EMLA application produced a satisfactory level of anesthesia in the palatal tissue when compared with the palatal injection.

Uncommon histopathological features of cytomegalovirus encephalitis and measles inclusion body encephalitis on autopsy in two patients with primary immunodeficiency.

PURPOSE: To describe the neuropathological findings in two patients with primary immunodeficiency who had fatal viral encephalitis. MATERIALS AND METHODS: Severe combined immunodeficiency (SCID) was confirmed in case 1 by genetic testing, while case 2 had features suggestive of combined immunodeficiency; however, whole exome sequencing showed no pathogenic variants. Autopsies were performed in both cases after an informed consent. A detailed sampling of the brain including extracranial organs was conducted. Immunohistochemistry and electron microscopy was also performed to confirm the presence of viruses. RESULTS: Besides evidence of cystic encephalomalacia observed in both cases, the brain in case 1 revealed cytomegalovirus (CMV) ventriculoencephalitis accompanied by an exuberant gemistocytic response in the entire white matter. Nuclei of gemistocytes were loaded with several CMV nuclear inclusions, which was confirmed by immunohistochemistry. Case 2 demonstrated features of measles inclusion body encephalitis with several viral inclusions within neurons and astrocytes. Rare giant cells were also seen. Measles virus was confirmed on immunohistochemistry and electron microscopy. Plausibly, there was paucity of microglial nodules in both cases. Superadded bacterial pneumonia with diffuse alveolar damage was also seen in both cases. CONCLUSION: These cases add to the spectrum of unusual histological features of viral encephalitis seen in patients with underlying primary immunodeficiency diseases.

Juvenile dermatomyositis associated with autoantibodies to small ubiquitin-like modifier activating enzyme: a report of 4 cases from North India and a review of literature.

BACKGROUND: Juvenile dermatomyositis (JDM) is the commonest inflammatory myositis in children. The clinical phenotype is often characterized by the presence of myositis-specific antibodies (MSA). Antibodies to small ubiquitin-like modifier activating enzyme (SAE) are amongst the rarest MSA reported in children. MATERIALS AND METHODS: A review of medical records of all patients diagnosed to have JDM during the period January 1992-April 2022 in our institute was done. Case records of children with JDM who had significant positivity for anti-SAE antibody by myositis immunoblot were analysed in detail. RESULTS: Of the 140 children with JDM, MSA immunoblot was carried out in 53 patients-4 (7.5%) amongst these had significant positivity for anti-SAE antibodies. Median age of onset of symptoms was 5.5 years (range: 5-11 years). Clinical features at presentation included fever, photosensitivity, heliotrope rash, and Gottron papules. Clinically significant proximal muscle weakness was noted in 3/4 patients; 1 had no discernible weakness but had radiological evidence of myositis. None of the 4 patients had evidence of interstitial lung disease or calcinosis. All patients were treated with intravenous pulse methylprednisolone: subcutaneous weekly methotrexate and hydroxychloroquine. One patient received mycophenolate mofetil because of a relapse of muscle disease, while none received cyclophosphamide or biologics. Median follow-up duration was 21.5 months (range: 6-39 months). CONCLUSION: Anti-SAE antibodies were found in 4/53 (7.5%) of North Indian children with JDM. All 4 patients had predominant cutaneous manifestations followed by muscle disease. Response to treatment was brisk and sustained. None had developed calcinosis in the follow-up. KEY MESSAGES: 1. We report high prevalence of anti-SAE antibody positivity (7.5%) in North Indian cohort of JDM. 2. Cutaneous disease precedes muscle weakness in children with anti-SAE positive JDM. 3. No evidence of interstitial lung disease/calcinosis was seen in these children.

Efficacy and safety of sufentanil sublingual tablet system in postoperative pain management: a systematic review and meta-analysis.

BACKGROUND: Sufentanil sublingual tablet system (SSTS) is a recently approved formulation for postoperative pain management that has become popular due to its pharmacokinetic properties such as good bioavailability, rapid attainment of equilibrium and elimination without any metabolites, along with its pharmacodynamic properties such as rapid onset and effective pain reduction. It is also relatively well tolerated by patients. OBJECTIVE: This is a quantitative analysis of the efficacy and safety of SSTS in patients with moderate to severe postoperative pain. DESIGN: This is a systematic review and meta-analysis. Databases such as Cochrane Library, MEDLINE and EMBASE were searched for eligible articles. SETTINGS: Randomised controlled trials published after 2000 in English language and which assessed at least one of the outcome measures of interest with pain intensity difference between 12 hours and a maximum of 96 hours. PARTICIPANTS: Adults with moderate to severe postoperative pain and taking SSTS for pain management. METHODS: Data were analysed using Review Manager (RevMan) V.5.3. Risk of bias (RoB) assessment was done using RoB-2 scale, and overall grading of evidence of each outcome was done using GRADEpro Guideline Development Tool. RESULTS: Analysis of SSTS versus control indicates a statistically significant reduction in summed pain intensity difference at 12 hours (mean difference (MD)=-12.33 (95% CI -15.5 to -9.17), p<0.00001), summed pain intensity difference at 48 hours (MD=-43.57 (95% CI -58.65 to -28.48), p<0.00001), time-weighted total pain relief over 12 hours (MD=-4.77 (95% CI -6.28 to -3.27), p<0.00001) and pain intensity difference (MD=-0.73 (95% CI -1.00 to -0.46), p<0.00001) with SSTS, alongside high quality of evidence. Success of treatment as assessed by Patient Global Assessment (OR=4.01 (95% CI 2.74 to 5.89), p<0.00001) and Healthcare Professional Global Assessment (OR=4.46 (95% CI 3.03 to 6.56), p<0.00001) scoring at 72 hours was observed in a significantly high number of individuals using SSTS, with high quality of evidence. There was no difference in adverse events except for dizziness (RR=1.90, 95% CI 1.02 to 3.52). There was a significantly higher number of total adverse events in orthopaedic surgery in the SSTS group than in the comparator. CONCLUSION: SSTS is effective in postoperative pain management in patients with moderate to severe pain. It also has good tolerability and high patient satisfaction. PROSPERO REGISTRATION NUMBER: CRD42018115458.

Alignment efficiency and three-dimensional assessment of root resorption after alignment with conventional and copper-nickel-titanium archwires: A randomized controlled trial

ABSTRACT Objective: To compare alignment efficiency and root resorption between nickel-titanium (NiTi) and copper-nickel-titanium (CuNiTi) archwires after complete alignment in mandibular anterior region. Methods: In this two-arm parallel single-blind randomized controlled trial, forty-four patients with Class I malocclusion with mandibular anterior crowding were recruited form orthodontic clinic of All India Institute of Medical Sciences (Jodhpur, India). Patients were randomly allocated into NiTi and CuNiTi groups, with a 1:1 allocation. Alignment was performed using 0.014-in, 0.016-in, 0.018-in, 0.019x0.025-in archwire sequence in the respective groups, which terminated in 0.019 x 0.025-in stainless-steel working archwire. The primary outcome was alignment efficiency, measured on study models from baseline (T0) to the first, second, third, fourth and fifth-month (T5). Secondary outcome was root resorption, measured from CBCT scans taken at T0 and T5. Mixed-factorial ANOVA was used to compare Little's Irregularity Index (LII). For assessing the proportion of patients with complete alignment at the end of each month, Kaplan-Meier survival curve was built and time to treatment completion was compared between groups using log rank test. Paired t-test was used to assess external apical root resorption (EARR) within groups, whereas independent t-test was used to evaluate LII and EARR between the groups. Results: Twenty-two patients were recruited in each group. One patient was lost to follow-up in the CuNiTi group. No statistically significant differences were observed in alignment efficiency between the groups (p>0.05). Intergroup comparison revealed that the changes in root measurement in three-dimensions were not statistically significant (p>0.05), except for mandibular right central incisor, which showed increased resorption at root apex in NiTi group (p<0.01). Conclusion: The two alignment archwires showed similar rate of alignment at all time points. Root resorption measurement did not differ between the NiTi and CuNiTi groups, except for the mandibular right central incisor, which showed more resorption in NiTi group.

RESUMO Objetivo: Comparar os fios de níquel-titânio (NiTi) e de cobre-níquel-titânio (CuNiTi) quanto à eficiência do alinhamento e quantidade de reabsorção radicular, após alinhamento completo dos dentes da região anterior inferior. Métodos: Neste estudo clínico randomizado, cego, paralelo, de dois braços, quarenta e quatro pacientes com má oclusão Classe I e apinhamento anterior inferior foram recrutados na clínica ortodôntica do All India Institute of Medical Sciences (Jodhpur, India). Os pacientes foram alocados aleatoriamente nos grupos NiTi e CuNiTi, na proporção de 1:1. O alinhamento foi realizado usando a sequência de fios 0,014", 0,016", 0,018" e 0,019" x 0,025" nos respectivos grupos, finalizando com o arco de trabalho 0,019" x 0,025" de aço inoxidável. O desfecho primário foi a eficiência do alinhamento, medida nos modelos de estudo nos tempos inicial (T0) e após um, dois, três, quatro e cinco meses (T5). O desfecho secundário foi a reabsorção radicular, medida a partir de tomografias computadorizadas realizadas em T0 e T5. ANOVA fatorial mista foi utilizada para comparar o Índice de Irregularidade de Little (IIL). Para avaliar a proporção de pacientes com alinhamento completo ao fim de cada mês, foi construída uma curva de sobrevida pelo método de Kaplan-Meier, e o tempo até o fim do tratamento foi comparado entre os grupos por meio do teste log-rank. Um teste t pareado foi utilizado para avaliar a reabsorção radicular apical externa (RRAE) dentro dos grupos, enquanto um teste t independente foi utilizado para avaliar o IIL e a RRAE entre os grupos. Resultados: Vinte e dois pacientes foram recrutados em cada grupo. Um paciente perdeu o acompanhamento no grupo CuNiTi. Não foram observadas diferenças estatisticamente significativas entre os grupos quanto à eficiência do alinhamento (p>0,05). A comparação intergrupos revelou que as alterações na RRAE medida em três dimensões não foram estatisticamente significativas (p>0,05), exceto para o incisivo central inferior direito, que apresentou aumento da RRAE no grupo NiTi (p<0,01). Conclusão: Os dois tipos de fios de alinhamento apresentaram taxa de alinhamento semelhante em todos os momentos. A medida da reabsorção radicular não diferiu entre o grupo NiTi e CuNiTi, exceto para o incisivo central inferior direito, que apresentou maior reabsorção no grupo NiTi.