Lymphoma at First Sight: A Rare Case of Mantle Cell Lymphoma Presenting as Isolated Periorbital Swelling

Mantle cell lymphoma (MCL) represents a heterogenous subtype of non-Hodgkin lymphoma (NHL), which can present in three distinct clinicopathologic variants: indolent type MCL, classic type MCL and blastoid type MCL. Despite the different variations, MCL, in general, is almost always associated with advanced-stage disease at diagnosis, with a strong predilection for significant extranodal involvement, usually to the bone marrow, CNS, peripheral blood and the gastrointestinal tract. However, the literature review reveals ocular involvement is a more rarely described extranodal site of involvement by MCL. Among the reported cases, the orbit was most commonly involved, followed by the eyelid and the lacrimal gland. We report a 63-year-old male who presented with a nine-month history of progressive symptoms of periorbital swelling and eyelid apraxia, causing bilateral visual disturbances. The patient was initially treated for presumed blepharospasm by his ophthalmologist with botulinum toxin injections; however, his periorbital edema continued to worsen, and he developed a discrete nodule in his right lower eyelid. Biopsy of the right eyelid nodule revealed classic type MCL with immunohistochemical testing positive for CD20, CD5, cyclin D1, SOX11 and Ki67 proliferative index of 40%. Fluorescence in situ hybridization (FISH) analysis detected (11;14) translocation. Mantle Cell Lymphoma International Prognostic Index Combined Biologic Index (MIPIb) score was calculated to be 6.5 points based on his age, ECOG performance status of 0-1, normal serum LDH, normal white blood cell count and elevated Ki67 proliferative index, stratifying patient into the high-risk group, with an estimated median overall survival of 37 months. Due to the bulky MCL involvement in the palpebral conjunctiva affecting his vision and eyelid function, he was immediately treated with radiation therapy to the bilateral orbits. PET-CT revealed adenopathy above and below the diaphragm. Bone marrow biopsy revealed focal involvement (5-10%) by MCL. Brain MRI revealed MCL infiltration in the bilateral orbits and lacrimal glands. Upper and lower endoscopy revealed multiple polyps positive for MCL. Given the advanced stage of the disease and his high-risk stratification, he was started on intensive induction chemotherapy with rituximab, dexamethasone, cytarabine, and carboplatin and received prophylactic intrathecal methotrexate. Systemic imaging after completion of four cycles of treatment revealed near resolution of the majority of the lymphadenopathy and all of the lymph nodes no longer demonstrated any significant metabolic activity. He completed two additional cycles of systemic chemotherapy and is currently being evaluated for autologous hematopoietic stem cell transplantation in complete remission-1 given his excellent response to treatment, his young age, high-risk disease at diagnosis, and good performance status. Despite the diffuse and extensive systemic disease, interestingly, our patient did not exhibit any constitutional or metastasis-associated symptoms and only presented with isolated periorbital swelling. Our case emphasizes the rare extranodal site of involvement by MCL and encourages all medical providers to remain cognizant of the varying ways in which MCL can present clinically

Ovarian sex cord stromal tumours in children and young girls - a more than two decade clinicopathological experience in a developing country, Pakistan

Background: Ovarian sex-cord stromal tumours (SCST) are rare, and relatively infrequent in children. These have to be distinguished from more common germ cell tumors in children and also from benign epithelial neoplasms.Objectives: The purpose of our study was to report the clinical and pathological findings in young patients with these tumours in our population.Material and Methods: The present observational cross-sectional study included all subjects SCST, in Aga Khan University Hospital Histopathology Laboratory, Karachi, Pakistan, from January 1992 till July 2013.Results: Of the total of 513 SCSTs presented during the study period, 39 fulfilled inclusion criteria and were assessed. The age range was 4-250 months. Most of the tumours presented at stage-1 and an abdominal mass was the most common presenting symptom, along with menstrual disturbance. The left side ovary was slightly more affected (53.5%). Of the total, 15 were juvenile granulosa cell tumours (JGCT), 11 sclerosing stromal tumours (SST), 10 of the fibrothecomas spectrum, 2 Sertoli leydig cell tumours (SLCT) and one a sex cord tumour with annular tubules (SCTAT). Detailed immunohistochemical analyses were performed in 33 cases. Recurrence/metastasis was noted in 4/21 cases with follow-up data.Conclusions: Ovarian sex cord stromal tumours are very rare in young age in our population, and usually present at an early stage. Most common among these are juvenile granulosa cell tumours, although surprisingly sclerosing stromal tumours were also common. Clinical symptoms due to hormone secretion in premenstrual girls and menstrual disturbance in menstruating girls are common presenting features

Clinicopathological spectrum of ovarian sex cord-stromal tumors; 20years\u27 retrospective study in a developing country

Background: Ovarian sex cord stromal tumors are rare neoplasms as compared to epithelial tumors. No large study has been done in Pakistan to find out the frequencies of various sex cord stromal tumors and their clinicopathological behavior in our region. The purpose of our study was to determine the various histological patterns and clinical features of ovarian sex cord stromal tumors along with follow-up in our set-up. Methods: It is a retrospective observational study. The study was conducted in section of Histopathology, Aga Khan University Hospital, Karachi, Pakistan. All reported cases of sex cord stromal tumors of ovary during 1992 to 2012 were retrieved. The retrieved slides were reviewed and patient demographics, clinical and pathological features were noted on proforma. SPSS Statistics Version 19 was used for all analyses. Data is expressed as absolute values and percentage or as mean ± standard deviation (SD). Results:A total of 480 cases of sex cord stromal tumors were retrieved. The median age was 45years. Bilaterality was observed in 4 cases. Of the different subtypes of sex-cord stromal tumors, most common was adult granulosa cell tumor 211(43.9%). 24 Juvenile granulosa cell tumors were retrieved (5%). Other types were fibromas 98 (20.4%) fibrothecomas 47(9.8%), thecomas 26(5.4%), sertoli-leydig cell tumors 34(7%), sclerosing stromal tumors 26 (5.4%), steroid cell tumors (10) and 4 cases of sex cord tumor with annular tubules. Of various immunohistochemical stains applied, Inhibin was frequently positive in all subtypes and focal cytokeratins were also seen commonly. Follow up information was available in 305 cases and out of these only 16 (5%) developed recurrence or metastasis. Conculsion: Sex cord stromal tumors are uncommon ovarian tumors in Pakistani population, with wide age range and diverse histological types having good prognosis. Immunohistochemical markers overlap with epithelial tumors so there is need to distinguish these two

It\u27s a precious gift, not to waste : Is routine cross matching necessary in orthopedics surgery?: Retrospective study of 699 patients in 9 different procedures

Background: Orthopedic surgeries are usually associated with excessive blood loss which leads surgeons to overestimate need for blood transfusions and over ordering of blood. The cross matched blood, when not used, leads to the wastage of blood bank resources in terms of time, money and manpower. The objective of this study was to investigate the compliance to previously proposed MSBOS and to provide updated recommendations for all orthopedic procedures. Methods: A retrospective analysis was conducted between 1st June 2015 and 31st May 2016. Patients admitted to the orthopedic surgery service for whom blood products were requested were included. Cross Match/Transfusion (CT) Ratio, Transfusion Index and Transfusion Probability were calculated. Values of \u3c 2.5, \u3e 0.5 and \u3e 30% respectively, were taken as standards. Maximum Surgical Blood Ordering Schedule (MSBOS) was proposed based upon these calculations using Mead\u27s criteria. Results: Six hundred and ninety-nine patients were sampled after implementing exclusion criteria. The overall CT ratio was 4.87, transfusion index was 0.55 and transfusion probability was 25%. A compliance rate of 24.6% was observed with the reference CT ratio of 2.5. Highest CT ratio was calculated for arthroscopic procedures while tumor resection had the lowest ratio. Age, procedure performed, ASA status and use of tourniquet were found to be significantly associated with CT ratio being greater or less than 2.5. Conclusion: Results showed significant wastage of blood products and non-compliance with blood ordering guidelines. Hence there is need for large scale prospective studies to establish MSBOS and ensure its compliance

General public awareness, knowledge and attitude toward COVID-19 infection and prevention: a cross-sectional study from Pakistan [version 2; peer review: 2 approved]

Background: The aim of this study is to evaluate the knowledge, perceptions, and attitude of the public in Pakistan (using social media) towards COVID-19. Methods: A cross-sectional study was conducted amongst 1120 individuals nationwide. A self-developed, pre-tested questionnaire was used that comprised of sections covering demographic characteristics, medical history, hygiene awareness, COVID-19-related knowledge, and learning attitude. Descriptive statistics were used for frequencies, percentages, averages and standard deviations. Inferential statistics were done using the Student’s t-test and ANOVA. Results: The average age of participants was 31 years (range 18-60 years). In total 56 individuals (5%) had completed primary or secondary school education; 448 (40%) were employed (working from home) and 60% were jobless due to the COVID-19 crisis. Almost all the study subjects (1030 (92%)) were washing their hands multiple times a day. A total of 83% had awareness regarding quarantine time, 82% used face masks whenever they left their homes, 98% were aware of the origin of the disease, and 70% had knowledge regarding the most common symptoms of COVID-19. Conclusion: It can be concluded from the current study that female participants had higher level of education, and more awareness regarding the coronavirus. The majority of the participants followed proper hand washing regimes and washed their faces. Further knowledge and awareness should be promoted

Global, regional, and national mortality due to unintentional carbon monoxide poisoning, 2000–2021: results from the Global Burden of Disease Study 2021

Background Unintentional carbon monoxide poisoning is a largely preventable cause of death that has received insufficient attention. We aimed to conduct a comprehensive global analysis of the demographic, temporal, and geographical patterns of fatal unintentional carbon monoxide poisoning from 2000 to 2021. Methods As part of the latest Global Burden of Diseases, Injuries, and Risk Factors Study (GBD), unintentional carbon monoxide poisoning mortality was quantified using the GBD cause of death ensemble modelling strategy. Vital registration data and covariates with an epidemiological link to unintentional carbon monoxide poisoning informed the estimates of death counts and mortality rates for all locations, sexes, ages, and years included in the GBD. Years of life lost (YLLs) were estimated by multiplying deaths by remaining standard life expectancy at age of death. Population attributable fractions (PAFs) for unintentional carbon monoxide poisoning deaths due to occupational injuries and high alcohol use were estimated. Findings In 2021, the global mortality rate due to unintentional carbon monoxide poisoning was 0·366 per 100 000 (95% uncertainty interval 0·276–0·415), with 28 900 deaths (21 700–32 800) and 1·18 million YLLs (0·886–1·35) across all ages. Nearly 70% of deaths occurred in males (20 100 [15 800–24 000]), and the 50–54-year age group had the largest number of deaths (2210 [1660–2590]). The highest mortality rate was in those aged 85 years or older with 1·96 deaths (1·38–2·32) per 100 000. Eastern Europe had the highest age-standardised mortality rate at 2·12 deaths (1·98–2·30) per 100 000. Globally, there was a 53·5% (46·2–63·7) decrease in the age-standardised mortality rate from 2000 to 2021, although this decline was not uniform across regions. The overall PAFs for occupational injuries and high alcohol use were 13·6% (11·9–16·0) and 3·5% (1·4–6·2), respectively. Interpretation Improvements in unintentional carbon monoxide poisoning mortality rates have been inconsistent across regions and over time since 2000. Given that unintentional carbon monoxide poisoning is almost entirely preventable, policy-level interventions that lower the risk of carbon monoxide poisoning events should be prioritised, such as those that increase access to improved heating and cooking devices, reduce carbon monoxide emissions from generators, and mandate use of carbon monoxide alarms.publishedVersio

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020