Multiomic Profiling of Human Clonal Hematopoiesis Reveals Genotype and Cell-Specific Inflammatory Pathway Activation.

Clonal hematopoiesis (CH) is an age-associated phenomenon that increases risk for hematologic malignancy and cardiovascular disease. CH is thought to enhance disease risk through inflammation in the peripheral blood1. Here, we profile peripheral blood gene expression in 66,968 single cells from a cohort of 17 CH patients and 7 controls. Using a novel mitochondrial DNA barcoding approach, we were able to identify and separately compare mutant TET2 and DNMT3A cells to non-mutant counterparts. We discovered the vast majority of mutated cells were in the myeloid compartment. Additionally, patients harboring DNMT3A and TET2 CH mutations possessed a pro-inflammatory profile in CD14+ monocytes through previously unrecognized pathways such as galectin and macrophage Inhibitory Factor (MIF). We also found that T cells from CH patients, though mostly un-mutated, had decreased expression of GTPase of the immunity associated protein (GIMAP) genes, which are critical to T cell development, suggesting that CH impairs T cell function.

IgA Vasculitis following AstraZeneca/Oxford COVID-19, case report.

Immunoglobulin A (IgA) vasculitis, also known as Henoch-Schönlein purpura, is an immune-mediated vasculitis that affects small vessels. IgA vasculitis could be triggered by numerous conditions including infectious and non-infectious conditions. So far, few reported cases of Covid-19 vaccines related vasculitis. We report a case of IgA vasculitis after AstraZeneca/Oxford COVID-19 vaccine. A 29-year-old healthy man who developed purpuric skin lesions one week after his second AstraZeneca/Oxford COVID-19 vaccine which complicated by glomerulonephritis and gastrointestinal involvement. Skin biopsy revealed fibrinoid necrosis and leukocytoclasia consistent with small vessel vasculitis. Due to the temporal association, AstraZeneca/Oxford COVID-19 vaccine-related IgA vasculitis would be the most likely explanation.

Assessment of Acute Side Effects Among 3D-Concurrent Radiotherapy With Cisplatin-Treated Head and Neck Cancer Patients.

INTRODUCTION: Three-dimensional conformal radiation therapy has become one of the basic components of multidisciplinary treatment for head and neck cancer. Generally, patients with squamous-cell carcinoma of the head and neck receive cisplatin-based chemoradiation. AIMS: In the current project, the goal was to assess 3D-CRT with cisplatin-induced acute side effects (dermatitis plus xerostomia) among head and neck cancer patients. METHODOLOGY: This descriptive case series was held at the Institute of Nuclear Medicine and Oncology, Lahore, Pakistan, with an enrollment of 106 head and neck cancer patients following the hospital's ethical approval. All patients received 3D-CRT with concurrent cisplatin chemotherapy according to the oncology treatment protocol at the Institute of Nuclear Medicine and Oncology. The evaluation of enrolled patients was done during treatment at a weekly interval and at one-month post-radiation. Stage 3 patients (17.9%) received chemo-radiation therapy with 40 mg/m2 cisplatin once weekly for seven weeks. All patients received 70 grays in 35 fractions with two grays per fraction over the course of seven weeks following a standard protocol. All enrolled cases had biopsy-proven squamous cell carcinoma of the head and neck. IBM Corp. Released 2015. IBM SPSS Statistics for Windows, Version 23.0. Armonk, NY: IBM Corp. analyzed the data. Chi-square and Fisher's exact tests were applied, while a p-value ≤ 0.05 was taken as statistically significant. RESULTS: All patients developed acute skin changes (dermatitis plus xerostomia) as a side effect of radiation therapy, with cisplatin having different grades during treatment until seven weeks. However, these changes improved and became less severe in terms of grade after one month of post-treatment among all patients. CONCLUSION: It was concluded that 3D-CRT was associated with dermatitis and xerostomia during and immediately after follow-up, even though the treatment response was good. However, clinical signs and symptoms improved, indicating that radiation therapy is a relatively safe treatment modality among cancer patients. Moreover, 40 mg/m2 cisplatin once weekly for seven weeks resulted in better loco-regional control and survival among advanced-stage head and neck cancer patients as a part of treatment. Although, higher doses of cisplatin (100 mg/m2 ) every three weeks have more harmful acute side effects and delay treatment for patients due to poor compliance.

Protease-Activated Receptor 2 (PAR2) Expressed in Sensory Neurons Contributes to Signs of Pain and Neuropathy in Paclitaxel Treated Mice.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common, dose-limiting side effect of cancer therapy. Protease-activated receptor 2 (PAR2) is implicated in a variety of pathologies, including CIPN. In this study, we demonstrate the role of PAR2 expressed in sensory neurons in a paclitaxel (PTX)-induced model of CIPN in mice. PAR2 knockout/wildtype (WT) mice and mice with PAR2 ablated in sensory neurons were treated with PTX administered via intraperitoneal injection. In vivo behavioral studies were done in mice using von Frey filaments and the Mouse Grimace Scale. We then examined immunohistochemical staining of dorsal root ganglion (DRG) and hind paw skin samples from CIPN mice to measure satellite cell gliosis and intra-epidermal nerve fiber (IENF) density. The pharmacological reversal of CIPN pain was tested with the PAR2 antagonist C781. Mechanical allodynia caused by PTX treatment was alleviated in PAR2 knockout mice of both sexes. In the PAR2 sensory neuronal conditional knockout (cKO) mice, both mechanical allodynia and facial grimacing were attenuated in mice of both sexes. In the DRG of the PTX-treated PAR2 cKO mice, satellite glial cell activation was reduced compared to control mice. IENF density analysis of the skin showed that the PTX-treated control mice had a reduction in nerve fiber density while the PAR2 cKO mice had a comparable skin innervation as the vehicle-treated animals. Similar results were seen with satellite cell gliosis in the DRG, where gliosis induced by PTX was absent in PAR cKO mice. Finally, C781 was able to transiently reverse established PTX-evoked mechanical allodynia. PERSPECTIVE: Our work demonstrates that PAR2 expressed in sensory neurons plays a key role in PTX-induced mechanical allodynia, spontaneous pain, and signs of neuropathy, suggesting PAR2 as a possible therapeutic target in multiple aspects of PTX CIPN.

Decreasing the Rate of Surgical Site Infection in Patients Operated by Cesarean Section in a Tertiary Care Hospital in India: A Quality Improvement Initiative.

Background Surgical site infections (SSIs) are a substantial cause of maternal morbidity and are associated with a significant increase in hospital stay and cost. The prevention of SSI is complex and requires the integration of a range of measures before, during, and after surgery. Jawaharlal Nehru Medical College (JNMC), Aligarh Muslim University (AMU) is one of the referral centers of India with a huge influx of patients. Methods The project was undertaken by the Department of Obstetrics and Gynaecology, JNMC, AMU, Aligarh. Our department was sensitized to the need for quality improvement (QI) through Laqshya, a Government of India initiative for labor rooms in 2018. We were facing problems like a high surgical site infection rate, poor documentation and records, no standard protocols, overcrowding, and no admission discharge policy. There was a high rate of surgical site infections, leading to maternal morbidity, increased days of hospitalization, more usage of antibiotics, and increased financial burden. A multidisciplinary quality improvement (QI) team was formed comprising obstetricians and gynecologists, the hospital infection control team, the head of the neonatology unit, staff nurses, and multitasking staff (MTS) workers. Results The baseline data were collected for a period of one month and it was found that the rate of SSI was around 30%. Our aim was to decrease the rate of SSI from 30% to less than 5% over a period of six months. The QI team worked meticulously, implemented evidence-based measures, regularly analyzed the results, and devised measures to overcome the obstacles. The point-of-care improvement (POCQI) model was adopted for the project. The rate of SSI decreased significantly in our patients and the rates are around 5% persistently. Conclusion The project not only helped in decreasing the infection rates but also led to vast improvements in the department with the formulation of an antibiotic policy, surgical safety checklist, and admission-discharge policy.

Cryptococcus Infection in an Immunocompetent Patient.

Cryptococcal meningitis is a fungal infection of the CNS, generally thought of as an opportunistic infection in those with T-cell immunodeficiencies including AIDS (usually with a CD4 count of less than 100), chronic steroid use, hematological malignancies, and transplant recipients. It can have irreversible CNS morbidity, including vision loss, intracranial hypertension, and cognitive decline. Diagnosis depends on cerebrospinal fluid (CSF) analysis, in which cultures and cryptococcal antigen are most sensitive. CSF PCR can also be done. Most patients have disseminated disease, and blood cultures are also positive. Outcomes remain guarded, with a poor prognosis (morbidity and high mortality) among survivors. This article presents a case of cryptococcal meningitis in an immunocompetent individual, where absolutely no identifiable risk factor was present.

A systematic review and meta-analysis assessing the impact of body mass index on long-term survival outcomes after surgery for colorectal cancer.

BACKGROUND: The impact of body mass index (BMI) on long-term survival outcomes after colorectal cancer surgery is debated. DESIGN: A systematic literature review and meta-analysis was performed to compare long-term survival outcomes of patients of different BMI categories after colorectal cancer surgery. RESULTS: Of the 2588 articles screened, 56 articles met the inclusion criteria, reporting on 72,582 participants. Patients with BMI <18.5 had significantly worse overall survival [hazard ratio (HR) 1.91; P < 0.0001], cancer-specific survival (HR = 1.91; P < 0.0001), disease-free survival (HR = 1.50; P < 0.0001) and recurrence-free survival (HR = 1.13; P = 0.007) compared to patients with a BMI of 18.5-25. There was no significant difference between those with BMI 25-30 and 18.5-25 in overall survival, cancer-specific survival, disease-free survival and recurrence-free survival, except for the subgroup of patients with colon cancer where patients with BMI 25-30 had significantly improved overall survival (HR = 0.90; P = 0.05) and disease-free survival (HR = 0.90; P = 0.04). Patients with BMI >30 had significantly worse disease-free survival (HR = 1.05; P = 0.03) compared to patients with a BMI of 18.5-25, but no significant difference in overall survival, cancer-specific survival and recurrence-free survival. Patients with BMI >35 compared to 18.5-25 had significantly worse overall survival (HR = 1.24; P = 0.02), cancer-specific survival (HR = 1.36; P = 0.01), disease-free survival (HR = 1.15; P = 0.03) and recurrence-free survival for colon (HR = 1.11; P = 0.04) and rectal (HR = 4.10; P = 0.04) cancer. CONCLUSIONS: Being underweight (BMI < 18.5) or class II/III obese (BMI > 35) at the time of colorectal cancer surgery may result in worse long-term survival outcomes, whereas being overweight (BMI 25-30) may improve survival in a subgroup of patients with colon cancer. Optimising BMI may preoperatively improve long-term survival after surgery for colorectal cancer.

Central Nervous System Involvement of Multiple Myeloma Presenting as Short-lasting Unilateral Neuralgiform Headache with Conjunctival Injection and Tearing: A Case Report.

Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT) and short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA) are part of the trigeminal autonomic cephalalgia (TAC) group of headache disorders. Attacks present with repeated, severe, sharp, stabbing, or throbbing pain. Patients may experience a single attack, recurrent attacks with pain-free interictal periods, or a sawtooth pattern background pain with superimposed stabs.1,2 Although SUNCT typically presents as a primary headache disorder, it may be secondary to an underlying pathology, such as pituitary tumors or posterior fossa lesions, both intra and extra-axial (vascular lesion, tumor, or bony abnormalities). Multiple Myeloma (MM) with central nervous system involvement (CNS MM) most commonly presents with visual changes (36%), radiculopathy (27%), headache (25%), confusion (21%), dizziness (7%) and seizures (6%).3,4 Secondary SUNCT cases have been sparsely described (less than 60), and CNS MM presenting as SUNCT has not been previously described in the literature.2,5 Our case describes a previously unreported clinical presentation of CNS MM. The report highlights the need for a timely and thorough diagnostic work-up of headache in patients with risk factors for a secondary etiology, which in this case included new-onset, autonomic features, older age, and history of malignancy. A misdiagnosis will preclude a potentially life-extending or saving targeted therapy for the underlying illness. We also aim to remind practitioners of the variability in the clinical symptoms of SUNCT, which are known to occur in a significant number of cases, including migrainous features and dull interictal pain.

Clinical Characteristics, Management Strategies, and Outcomes of Non-ST-Segment-Elevation Myocardial Infarction Patients With and Without Prior Coronary Artery Bypass Grafting.

Background There are limited data on the management strategies, temporal trends and clinical outcomes of patients who present with non-ST-segment-elevation myocardial infarction and have a prior history of CABG. Methods and Results We identified 287 658 patients with non-ST-segment-elevation myocardial infarction between 2010 and 2017 in the United Kingdom Myocardial Infarction National Audit Project database. Clinical and outcome data were analyzed by dividing into 2 groups by prior history of coronary artery bypass grafting (CABG): group 1, no prior CABG (n=262 362); and group 2, prior CABG (n=25 296). Patients in group 2 were older, had higher GRACE (Global Registry of Acute Coronary Events) risk scores and burden of comorbid illnesses. More patients underwent coronary angiography (69% versus 63%) and revascularization (53% versus 40%) in group 1 compared with group 2. Adjusted odds of receiving inpatient coronary angiogram (odds ratio [OR], 0.91; 95% CI, 0.88-0.95; P<0.001) and revascularization (OR, 0.73; 95% CI, 0.70-0.76; P<0.001) were lower in group 2 compared with group 1. Following multivariable logistic regression analyses, the OR of in-hospital major adverse cardiovascular events (composite of inpatient death and reinfarction; OR, 0.97; 95% CI, 0.90-1.04; P=0.44), all-cause mortality (OR, 0.96; 95% CI, 0.88-1.04; P=0.31), reinfarction (OR, 1.02; 95% CI, 0.89-1.17; P=0.78), and major bleeding (OR, 1.01; 95% CI, 0.90-1.11; P=0.98) were similar across groups. Lower adjusted risk of inpatient mortality (OR, 0.67; 95% CI, 0.46-0.98; P=0.04) but similar risk of bleeding (OR,1.07; CI, 0.79-1.44; P=0.68) and reinfarction (OR, 1.13; 95% CI, 0.81-1.57; P=0.47) were observed in group 2 patients who underwent percutaneous coronary intervention compared with those managed medically. Conclusions In this national cohort, patients with non-ST-segment-elevation myocardial infarction with prior CABG had a higher risk profile, but similar risk-adjusted in-hospital adverse outcomes compared with patients without prior CABG. Patients with prior CABG who received percutaneous coronary intervention had lower in-hospital mortality compared with those who received medical management.

Diagnostic dilemma: COVID-19 related cardiomyopathy or peripartum cardiomyopathy?

Peripartum cardiomyopathy is a relatively rare condition, that usually presents with features of heart failure in the peripartum period. The ongoing pandemic caused by coronavirus disease 2019 (COVID-19) has been reported to be associated with myocarditis, with progression to dilated cardiomyopathy and heart failure. Dilated cardiomyopathy in a peripartum patient with COVID-19 infection may present a diagnostic dilemma. We report a case of dilated cardiomyopathy in a peripartum patient with COVID-19 infection. She presented with shortness of breath in the peripartum period. Chest X-ray showed a grossly enlarged heart with bilateral pulmonary infiltrates consistent with congestive heart failure or viral pneumonia. Echocardiography revealed dilated chambers with 22% left ventricular ejection fraction (LVEF) and global hypokinesis. Despite completing 5 days of remdesivir and dexamethasone, she had worsening dyspnea on postpartum day 10, a repeat echocardiogram showed further reduction in LVEF to 10-15% and was discharged with a life-vest after acute management. She had multiple hospital admissions for decompensated heart failure. Myocardial core biopsy showed marked acute inflammation and necrosis. She had an intra-aortic balloon pump, left ventricular and right ventricular assist devices placed on account of persistent hemodynamic instability, and is now scheduled to have a cardiac transplant. .

Role of miRNAs in cervical cancer: A comprehensive novel approach from pathogenesis to therapy.

Human papillomaviruses (HPV) infection is a major causative agent and strongly associated with the development of cervical cancer. Understanding the mechanisms of HPV-induced cervical cancer is extremely useful in therapeutic strategies for primary prevention (HPV vaccines) and secondary prevention (screening and diagnosis of precancerous lesions). However, due to the lack of proper implementation of screening programs in developing countries, cervical cancer is usually diagnosed at advanced stages that result in poor treatment responses. Nearly half of the patients will experience disease recurrence within two years post treatment. Therefore, it is vital to identify new tools for early diagnosis, prognosis, and treatment prediction. MicroRNAs (miRNAs) are small non-coding RNAs, implicated in posttranscriptional regulation of gene expression. Growing evidence has shown that abnormal miRNA expression is associated with cervical cancer progression, metastasis, and influences treatment outcomes. In this review, we provide comprehensive information about miRNA and their potential utility in cervical cancer diagnosis, prognosis, and clinical management to improve patient outcomes.

Biomarkers in Migraine.

BACKGROUND: Disability from migraine has a profound impact on the world's economy. Research has been ongoing to identify biomarkers to aid in diagnosis and treatment. OBJECTIVE: The aim of this study was to highlight the purported diagnostic and therapeutic migraine biomarkers and their role in precision medicine. METHODS: A comprehensive literature search was conducted using PubMed, Google Scholar, and clinicaltrials.gov using keywords: "migraine" OR "headache" combined with "biomarkers" OR "marker." Other keywords included "serum," "cerebral spinal fluid," "inflammatory," and "neuroimaging." RESULTS: After a review of 88 papers, we find the literature supports numerous biomarkers in the diagnosis of migraine. Therapeutic biomarkers, while not as extensively published, highlight calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating peptide-38 (PACAP-38) as biomarkers with the most substantiated clinical relevance. Genetic markers mainly focusing on gene mutations with resultant biochemical alterations continue to be studied and show promise. CONCLUSION: Although there are several proposed biomarkers for migraine, continued research is needed to substantiate their role in clinical practice.

A cautionary tale of pyridoxine toxicity in cystathionine beta-synthase deficiency detected by two-tier newborn screening highlights the need for clear pyridoxine dosing guidelines.

Classic homocystinuria is due to deficiency of cystathionine beta-synthase (CBS), a pyridoxine-dependent enzyme that, depending on the molecular variants, may be co-factor responsive. Elevated methionine is often used as the primary analyte to detect CBS deficiency (CBSD) on newborn screening (NBS), but is limited by increased detection of other biochemical disorders with less clear clinical significance such as methionine aminotransferase (MAT) I/III heterozygotes. Our state has implemented a two-tier NBS algorithm for CBSD that successfully reduced the number of MATI/III heterozygotes, yet effectively detected a mild, co-factor responsive form of CBSD. After initial diagnosis, newborns with CBSD often undergo a pyridoxine challenge with high-dose pyridoxine to determine responsiveness. Here we describe our NBS-identified patient with a mild form of pyridoxine responsive CBSD who developed respiratory failure and rhabdomyolysis consistent with pyridoxine toxicity during a pyridoxine challenge. This case highlights the need for weight-based dosing and duration recommendations for pyridoxine challenge in neonates.

Frequency of Mucositis Among Head and Neck Cancer Patients Receiving Three-Dimensional (3D) Radiotherapy.

Background and objective Head and neck cancer can arise from any site like hypo-pharynx, oro-pharynx, lip, oral cavity, or larynx. Almost 90% of them are head and neck squamous cell carcinomas (HNSCC). In the current project, the goal was to determine the frequency of acute side effects in terms of mucositis during and immediately post-irradiation period in patients receiving concurrent three-dimensional (3D) radiotherapy in a tertiary care hospital.  Methodology This descriptive case series with 106 enrolled patients was carried out from December 2019 to May 2020 at the Department of Radiation Oncology following approval. All patients were given radiotherapy or chemo-radio-therapy as per the clinician's advice and hospital protocol. All patients were evaluated at pre radiation time, at weekly intervals during treatment and at 11 weeks from 1st radiation fraction. Data was entered and analyzed by Statistical Package for Social Sciences, version 20 (SPSS Inc., Chicago, IL). Chi-square and Fisher's exact test was applied as p-value ≤ 0.05 was considered significant.  Results In the present study, all patients (n=106) showed a mean age of 57.8 ± 8.3 years. There was a gradual increase in grades of mucositis in all patients after treatments until seven weeks. After one month of post-treatment, a decrease in grades of mucositis was observed in all patients.  Conclusion Acute side effects appeared in all patients receiving 3D radiation therapy (RT) although the treatment response was good. Hence, we concluded it has a high incidence of treatment-related toxicities but it is safe.

Vertical distribution and radiological risk assessment of 137Cs and natural radionuclides in soil samples.

The aims of this study were to investigate the vertical distributions of natural radionuclides 232Th, 226Ra and 40K as well as anthropogenic radionuclide 137Cs in soil samples and to analyze the correlation among the radioactivity of these radionuclides and the physiochemical characteristics of soil samples namely pH, grain size, carbonate content and organic matter. Risk assessment of the radiological hazard has also been estimated. Forty-four soil samples were collected from eleven locations in Qatar at four depth levels from 0 to 16 cm. The average concentrations of 232Th, 226Ra, 40K and 137Cs in the soil depth of 16 cm were 10, 17, 201 and 4 Bq/kg, respectively, which were within the reported world mean. The external absorbed gamma dose rate, the annual effective dose, the mean radium equivalent activity, the external hazard index and the lifetime cancer risk were 22 nGy/h, 0.027 mSv/y, 47 Bq/kg, 0.125 and 0.096 × 10-3, respectively. These values were far below the minimum recommended international values. The level of radioactivity concentrations in the soil was affected by the physiochemical characteristics of the soil. The positive correlation with highest R2 value was found among the radioactivity concentrations of 232Th and 40K and the soil clay content. Total organic carbon was also positively correlated for 226Ra and 137Cs activity concentrations, whereas, carbonate content was negatively correlated with the radioactivity concentrations of 232Th and 40K. As far as soil moisture content is concerned, the positive correlation with highest R2 value was obtained for 226Ra activity concentrations.

Nociceptor Translational Profiling Reveals the Ragulator-Rag GTPase Complex as a Critical Generator of Neuropathic Pain.

Nociceptors, sensory neurons in the DRG that detect damaging or potentially damaging stimuli, are key drivers of neuropathic pain. Injury to these neurons causes activation of translation regulation signaling, including the mechanistic target of rapamycin complex 1 (mTORC1) and mitogen-activated protein kinase interacting kinase (MNK) eukaryotic initiation factor (eIF) 4E pathways. This is a mechanism driving changes in excitability of nociceptors that is critical for the generation of chronic pain states; however, the mRNAs that are translated to lead to this plasticity have not been elucidated. To address this gap in knowledge, we used translating ribosome affinity purification in male and female mice to comprehensively characterize mRNA translation in Scn10a-positive nociceptors in chemotherapy-induced neuropathic pain (CIPN) caused by paclitaxel treatment. This unbiased method creates a new resource for the field, confirms many findings in the CIPN literature and also find extensive evidence for new target mechanisms that may cause CIPN. We provide evidence that an underlying mechanism of CIPN is sustained mTORC1 activation driven by MNK1-eIF4E signaling. RagA, a GTPase controlling mTORC1 activity, is identified as a novel target of MNK1-eIF4E signaling. This demonstrates a novel translation regulation signaling circuit wherein MNK1-eIF4E activity drives mTORC1 via control of RagA translation. CIPN and RagA translation are strongly attenuated by genetic ablation of eIF4E phosphorylation, MNK1 elimination or treatment with the MNK inhibitor eFT508. We identify a novel translational circuit for the genesis of neuropathic pain caused by chemotherapy with important implications for therapeutics.SIGNIFICANCE STATEMENT Neuropathic pain affects up to 10% of the population, but its underlying mechanisms are incompletely understood, leading to poor treatment outcomes. We used translating ribosome affinity purification technology to create a comprehensive translational profile of DRG nociceptors in naive mice and at the peak of neuropathic pain induced by paclitaxel treatment. We reveal new insight into how mechanistic target of rapamycin complex 1 is activated in neuropathic pain pointing to a key role of MNK1-eIF4E-mediated translation of a complex of mRNAs that control mechanistic target of rapamycin complex 1 signaling at the surface of the lysosome. We validate this finding using genetic and pharmacological techniques. Our work strongly suggests that MNK1-eIF4E signaling drives CIPN and that a drug in human clinical trials, eFT508, may be a new therapeutic for neuropathic pain.

Postpartum Intrauterine Device Refusal in Delhi: Reasons Analyzed.

AIM: To assess knowledge and attitude of women toward postpartum intrauterine contraceptive device (PPIUCD) and analyze reasons of refusal. SETTING AND DESIGN: Hospital-based cross-sectional study for 1 year. MATERIALS AND METHODS: 550 women were enrolled in the study. Sociodemographic characteristics, knowledge, and attitude toward contraception especially PPIUCD were noted, and the reasons for refusal of PPIUCD were analyzed. STATISTICAL ANALYSIS: SPSS version 17.0 is used. Continuous variables were reported using mean, and categorical variables were reported using percentages. OBSERVATIONS: PPIUCD insertion rate was 9.1 %. 78.6 % of women in the study belonged to the age group of 20-30 years, with 79.2 % having education of Class X and above. The overall contraceptive knowledge was 94.4 %. Although 48.4 % women were aware of Cu T as a method of contraception, only 21.9 % of 48.4 %, however, were aware of PPIUCD. None of the women had ever used it before. The commonest prevalent myths regarding Cu T were fear of malignancy (38 %) and fear of menorrhagia (36.4 %). The husband and mother-in-law played important roles in decision regarding PPIUCD insertion and refused the same in 59 % of cases. CONCLUSION: The study shows that awareness of PPIUCD is low in this region despite good education, leading to high refusal rates. The commonest reason is lack of appropriate counseling, and not only the woman but the husband and mother-in-law also must be provided the knowledge of it as they play important roles in our society.

Comparison of Topical Versus Peribulbar Anesthesia for 23G Pars Plana Vitrectomy.

OBJECTIVE: To compare the safety and efficacy of topical anesthesia versus peribulbar anesthesia for 23-gauge pars plana vitrectomy. STUDY DESIGN: Randomized controlled trial. PLACE AND DURATION OF STUDY: Ophthalmology Department, Lahore General Hospital, Ameer-ud-Din Medical College, Postgraduate Medical Institute, Lahore from April 2013 to March 2016. METHODOLOGY: A total of 110 patients were equally divided (n=55) in group A (topical anesthesia) and group B (peribulbar anesthesia). In group A, pledget soaked with 0.5% proparacaine hydrochloride were placed in the superior and inferior fornices three minutes before surgery, and removed just before surgery. For group B patients, 3 ml of 0.5% bupivacaine was used for peribulbar anesthesia three minutes before surgery. Surgical time was noted from the placement of pledget in fornix till the eye pad placed in group A, and from the time of peribulbar anesthesia in group B till the eye pad placed at the end of surgery. All data was recorded in Excel sheet and p-values were calculated using online OpenEpi. RESULTS: The mean age of the patient was 56.28 ±13.76 years. Male patients were 78 (70.9%) and female patients were 32 (29.1%). Mean duration of surgery was 30.32 ±7.07 minutes and mean pain score was 2.30 ±0.98. There was a significant difference with respect to mean duration of surgery in patients who were given topical anesthesia (32.52 ±6.92 minutes) versus those given peribulbar anesthesia (28.12 ±6.57 minutes, p<0.001). Mean pain score in topical anesthesia group (3.11 ±0.89) was significantly higher as compared to peribulbar anesthesia group (2.67 ±0.91, p=0.011). CONCLUSION: Topical anesthesia is as effective as peribulbar anesthesia in terms of patient comfort and duration of surgery for 23-G pars plana vitrectomy in patients with vitreous hemorrhage.

Clinical characterization of novel chromosome 22q13 microdeletions.

INTRODUCTION: The advent of chromosome microarray analysis (CMA) for evaluation of patients with multiple congenital anomalies has made it possible to define chromosomal imbalances with greater precision and resolutions significantly smaller than possible by standard G-banded chromosome analysis. We describe two patients with novel chromosomal anomalies involving chromosome 22q13, a locus also associated with Phelan-McDermid syndrome (PMS). OBJECTIVE: We aim to characterize the novel phenotypic and genotypic findings of two patients with 22q13 microdeletions, distinct from PMS, comparing and contrasting with features of PMS. RESULTS: Case 1 is a 4-year-old boy with global developmental delay, esotropia, moderate aortic root dilation, genu valgum, and in-toeing gait. MRI brain for evaluation of neonatal hypotonia revealed a left cerebellopontine angle arachnoid cyst. He referred on newborn hearing screening, and diagnostic auditory brainstem response (ABR) showed left profound retrocochlear hearing loss. Surgical intervention for the arachnoid cyst was deferred, with spontaneous resolution at age two years without hearing recovery. CMA revealed a novel, de novo 5.1 Mb microdeletion of 22q13.31q13.33 not involving SHANK3, a gene typically deleted in PMS. Case 2 is a 6-year-old girl with some features also seen in patients with PMS but also several atypical features. She has a complex chromosomal rearrangement including a 5.3 Mb 22q13 microdeletion (not including SHANK3) and de novo 2.1 Mb gain of 22q11. CONCLUSION: As diagnostic sensitivity improves, smaller chromosomal imbalances will be detectable related to milder or different phenotypes. We present two patients with novel deletions of chromosome 22q13 associated with multiple congenital anomalies and features distinct from PMS.