Aga Khan University Hospital

Villar J., Ariff S., Gunier R.B., Thiruvengadam R., Rauch S., Kholin A., Roggero P., Prefumo F., do Vale M.S., Cardona-Perez J.A., Maiz N., Cetin I., Savasi V., Deruelle P., Easter S.R., et. al.

Detailed information about the association of COVID-19 with outcomes in pregnant individuals compared with not-infected pregnant individuals is much needed.To evaluate the risks associated with COVID-19 in pregnancy on maternal and neonatal outcomes compared with not-infected, concomitant pregnant individuals.In this cohort study that took place from March to October 2020, involving 43 institutions in 18 countries, 2 unmatched, consecutive, not-infected women were concomitantly enrolled immediately after each infected woman was identified, at any stage of pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed up until hospital discharge.COVID-19 in pregnancy determined by laboratory confirmation of COVID-19 and/or radiological pulmonary findings or 2 or more predefined COVID-19 symptoms.The primary outcome measures were indices of (maternal and severe neonatal/perinatal) morbidity and mortality; the individual components of these indices were secondary outcomes. Models for these outcomes were adjusted for country, month entering study, maternal age, and history of morbidity.A total of 706 pregnant women with COVID-19 diagnosis and 1424 pregnant women without COVID-19 diagnosis were enrolled, all with broadly similar demographic characteristics (mean [SD] age, 30.2 [6.1] years). Overweight early in pregnancy occurred in 323 women (48.6%) with COVID-19 diagnosis and 554 women (40.2%) without. Women with COVID-19 diagnosis were at higher risk for preeclampsia/eclampsia (relative risk [RR], 1.76; 95% CI, 1.27-2.43), severe infections (RR, 3.38; 95% CI, 1.63-7.01), intensive care unit admission (RR, 5.04; 95% CI, 3.13-8.10), maternal mortality (RR, 22.3; 95% CI, 2.88-172), preterm birth (RR, 1.59; 95% CI, 1.30-1.94), medically indicated preterm birth (RR, 1.97; 95% CI, 1.56-2.51), severe neonatal morbidity index (RR, 2.66; 95% CI, 1.69-4.18), and severe perinatal morbidity and mortality index (RR, 2.14; 95% CI, 1.66-2.75). Fever and shortness of breath for any duration was associated with increased risk of severe maternal complications (RR, 2.56; 95% CI, 1.92-3.40) and neonatal complications (RR, 4.97; 95% CI, 2.11-11.69). Asymptomatic women with COVID-19 diagnosis remained at higher risk only for maternal morbidity (RR, 1.24; 95% CI, 1.00-1.54) and preeclampsia (RR, 1.63; 95% CI, 1.01-2.63). Among women who tested positive (98.1% by real-time polymerase chain reaction), 54 (13%) of their neonates tested positive. Cesarean delivery (RR, 2.15; 95% CI, 1.18-3.91) but not breastfeeding (RR, 1.10; 95% CI, 0.66-1.85) was associated with increased risk for neonatal test positivity.In this multinational cohort study, COVID-19 in pregnancy was associated with consistent and substantial increases in severe maternal morbidity and mortality and neonatal complications when pregnant women with and without COVID-19 diagnosis were compared. The findings should alert pregnant individuals and clinicians to implement strictly all the recommended COVID-19 preventive measures.

Meherali S., Punjani N., Louie-Poon S., Abdul Rahim K., Das J.K., Salam R.A., Lassi Z.S.

Background: The COVID‑19 pandemic and associated public health measures have disrupted the lives of people around the world. It is already evident that the direct and indirect psychological and social effects of the COVID‑19 pandemic are insidious and affect the mental health of young children and adolescents now and will in the future. The aim and objectives of this knowledge-synthesis study were to identify the impact of the pandemic on children’s and adolescent’s mental health and to evaluate the effectiveness of different interventions employed during previous and the current pandemic to promote children’s and adolescents’ mental health. Methodology: We conducted the systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and included experimental randomized and nonrandomized controlled trials, observational studies, and qualitative studies. Results: Of the 5828 articles that we retrieved, 18 articles met the inclusion criteria. We thematically analyzed them and put the major findings under the thematic areas of impact of the pandemic on children’s and adolescents’ mental health. These studies reported that pandemics cause stress, worry, helplessness, and social and risky behavioral problems among children and adolescents (e.g., substance abuse, suicide, relationship problems, academic issues, and absenteeism from work). Interventions such as art-based programs, support services, and clinician-led mental health and psychosocial services effectively decrease mental health issues among children and adolescents. Conclusion: Children and adolescents are more likely to experience high rates of depression and anxiety during and after a pandemic. It is critical that future researchers explore effective mental health strategies that are tailored to the needs of children and adolescents. Explorations of effective channels regarding the development and delivery of evidenced-based, age-appropriate services are vital to lessen the effects and improve long-term capacities for mental health services for children and adolescents. Key Practitioner Message: The COVID-19 pandemic’s physical restrictions and social distancing measures have affected each and every domain of life. Although the number of children and adolescents affected by the disease is small, the disease and the containment measures such as social distancing, school closure, and isolation have negatively impacted the mental health and well-being of children and adolescents. The impact of COVID-19 on the mental health of children and adolescents is of great concern. Anxiety, depression, disturbances in sleep and appetite, as well as impairment in social interactions are the most common presentations. It has been indicated that compared to adults, this pandemic may continue to have increased long term adverse consequences on children’s and adolescents’ mental health. As the pandemic continues, it is important to monitor the impact on children’s and adolescents’ mental health status and how to help them to improve their mental health outcomes in the time of the current or future pandemics.

El‐Boghdadly K., Wong D.J., Owen R., Neuman M.D., Pocock S., Carlisle J.B., Johnstone C., Andruszkiewicz P., Baker P.A., Biccard B.M., Bryson G.L., Chan M.T., Cheng M.H., Chin K.J., Coburn M., et. al.

Healthcare workers involved in aerosol-generating procedures, such as tracheal intubation, may be at elevated risk of acquiring COVID-19. However, the magnitude of this risk is unknown. We conducted a prospective international multicentre cohort study recruiting healthcare workers participating in tracheal intubation of patients with suspected or confirmed COVID-19. Information on tracheal intubation episodes, personal protective equipment use and subsequent provider health status was collected via self-reporting. The primary endpoint was the incidence of laboratory-confirmed COVID-19 diagnosis or new symptoms requiring self-isolation or hospitalisation after a tracheal intubation episode. Cox regression analysis examined associations between the primary endpoint and healthcare worker characteristics, procedure-related factors and personal protective equipment use. Between 23 March and 2 June 2020, 1718 healthcare workers from 503 hospitals in 17 countries reported 5148 tracheal intubation episodes. The overall incidence of the primary endpoint was 10.7% over a median (IQR [range]) follow-up of 32 (18-48 [0-116]) days. The cumulative incidence within 7, 14 and 21 days of the first tracheal intubation episode was 3.6%, 6.1% and 8.5%, respectively. The risk of the primary endpoint varied by country and was higher in women, but was not associated with other factors. Around 1 in 10 healthcare workers involved in tracheal intubation of patients with suspected or confirmed COVID-19 subsequently reported a COVID-19 outcome. This has human resource implications for institutional capacity to deliver essential healthcare services, and wider societal implications for COVID-19 transmission.

Ahmad Z., Rahim S., Zubair M., Abdul-Ghafar J.

The role of Artificial intelligence (AI) which is defined as the ability of computers to perform tasks that normally require human intelligence is constantly expanding. Medicine was slow to embrace AI. However, the role of AI in medicine is rapidly expanding and promises to revolutionize patient care in the coming years. In addition, it has the ability to democratize high level medical care and make it accessible to all parts of the world. Among specialties of medicine, some like radiology were relatively quick to adopt AI whereas others especially pathology (and surgical pathology in particular) are only just beginning to utilize AI. AI promises to play a major role in accurate diagnosis, prognosis and treatment of cancers. In this paper, the general principles of AI are defined first followed by a detailed discussion of its current role in medicine. In the second half of this comprehensive review, the current and future role of AI in surgical pathology is discussed in detail including an account of the practical difficulties involved and the fear of pathologists of being replaced by computer algorithms. A number of recent studies which demonstrate the usefulness of AI in the practice of surgical pathology are highlighted. AI has the potential to transform the practice of surgical pathology by ensuring rapid and accurate results and enabling pathologists to focus on higher level diagnostic and consultative tasks such as integrating molecular, morphologic and clinical information to make accurate diagnosis in difficult cases, determine prognosis objectively and in this way contribute to personalized care.

Villar J., Soto Conti C.P., Gunier R.B., Ariff S., Craik R., Cavoretto P.I., Rauch S., Gandino S., Nieto R., Winsey A., Menis C., Rodriguez G.B., Savasi V., Tug N., Deantoni S., et. al.

SummaryBackground In 2021, we showed an increased risk associated with COVID-19 in pregnancy. Since then, the SARS-CoV-2 virus has undergone genetic mutations. We aimed to examine the effects on maternal and perinatal outcomes of COVID-19 during pregnancy, and evaluate vaccine effectiveness, when omicron (B.1.1.529) was the variant of concern. Methods INTERCOVID-2022 is a large, prospective, observational study, involving 41 hospitals across 18 countries. Each woman with real-time PCR or rapid test, laboratory-confirmed COVID-19 in pregnancy was compared with two unmatched women without a COVID-19 diagnosis who were recruited concomitantly and consecutively in pregnancy or at delivery. Mother and neonate dyads were followed until hospital discharge. Primary outcomes were maternal morbidity and mortality index (MMMI), severe neonatal morbidity index (SNMI), and severe perinatal morbidity and mortality index (SPMMI). Vaccine effectiveness was estimated, adjusted by maternal risk profile. Findings We enrolled 4618 pregnant women from Nov 27, 2021 (the day after WHO declared omicron a variant of concern), to June 30, 2022: 1545 (33%) women had a COVID-19 diagnosis (median gestation 36·7 weeks [IQR 29·0–38·9]) and 3073 (67%) women, with similar demographic characteristics, did not have a COVID-19 diagnosis. Overall, women with a diagnosis had an increased risk for MMMI (relative risk [RR] 1·16 [95% CI 1·03–1·31]) and SPMMI (RR 1·21 [95% CI 1·00–1·46]). Women with a diagnosis, compared with those without a diagnosis, also had increased risks of SNMI (RR 1·23 [95% CI 0·88–1·71]), although the lower bounds of the 95% CI crossed unity. Unvaccinated women with a COVID-19 diagnosis had a greater risk of MMMI (RR 1·36 [95% CI 1·12–1·65]). Severe COVID-19 symptoms in the total sample increased the risk of severe maternal complications (RR 2·51 [95% CI 1·84–3·43]), perinatal complications (RR 1·84 [95% CI 1·02–3·34]), and referral, intensive care unit (ICU) admission, or death (RR 11·83 [95% CI 6·67–20·97]). Severe COVID-19 symptoms in unvaccinated women increased the risk of MMMI (RR 2·88 [95% CI 2·02–4·12]) and referral, ICU admission, or death (RR 20·82 [95% CI 10·44–41·54]). 2886 (63%) of 4618 total participants had at least a single dose of any vaccine, and 2476 (54%) of 4618 had either complete or booster doses. Vaccine effectiveness (all vaccines combined) for severe complications of COVID-19 for all women with a complete regimen was 48% (95% CI 22–65) and 76% (47–89) after a booster dose. For women with a COVID-19 diagnosis, vaccine effectiveness of all vaccines combined for women with a complete regimen was 74% (95% CI 48–87) and 91% (65–98) after a booster dose. Interpretation COVID-19 in pregnancy, during the first 6 months of omicron as the variant of concern, was associated with increased risk of severe maternal morbidity and mortality, especially among symptomatic and unvaccinated women. Women with complete or boosted vaccine doses had reduced risk for severe symptoms, complications, and death. Vaccination coverage among pregnant women remains a priority. Funding None.

Tariq M.U., Din N.U., Abdul-Ghafar J., Park Y.

Solitary Fibrous Tumor (SFT) is a distinct soft tissue neoplasm associated with NAB2-STAT6 gene fusion. It can involve a number of anatomic sites and exhibits a wide spectrum of histological features. Apart from diversity in morphological features seen even in conventional SFT, two histologic variants (fat-forming and giant cell-rich) are also recognized. In addition, a malignant form and dedifferentiation are well recognized. Owing to diverse histological features and involvement of diverse anatomic locations, SFT can mimic other soft tissue neoplasms of different lineages including schwannoma, spindle cell lipoma, dermatofibrosarcoma protuberans, liposarcoma, gastrointestinal stromal tumor (GIST), malignant peripheral nerve sheath tumor (MPNST), and synovial sarcoma. SFT is classified as an intermediate (rarely metastasizing) tumor according to World Health Organization Classification of Tumors of Soft tissue and Bone, 5th edition. The management and prognosis of SFT differs from its malignant mimics and correct diagnosis is therefore important. Although SFT expresses a distinct immunohistochemical (IHC) profile, the classic histomorphological and IHC profile is not seen in all cases and diagnosis can be challenging. NAB2-STAT6 gene fusion has recently emerged as a sensitive and specific molecular marker and its IHC surrogate marker signal transducer and activator of transcription 6 (STAT6) has also shown significant sensitivity and specificity. However, few recent studies have reported STAT6 expression in other soft tissue neoplasms. This review will focus on describing the diversity of histological features of SFT, differential diagnoses and discussing the features helpful in distinguishing SFT from its histological mimics.

Ahmad M., Iram K., Jabeen G.

The researches investigating the influence factors of epidemic prevention are not only scarce, but also provide a gap in the domain of perception-based influence factors of intention to adopt COVID-19 epidemic prevention. This work has attempted to examine the perception-based influence factors of individuals’ intention to adopt COVID-19 epidemic prevention in a modified behavioral framework. A behavioral framework composed of the theory of reasoned action and the theory of planned behavior is developed to incorporate some additional perception-based influence factors. A partial least square-based path analysis has been employed to estimate the path coefficients of those factors in terms of drivers, barriers, and neutral factors based on questionnaire data of 302 respondents from six universities and two hospitals in China. Among the perception-based influence factors, governments' guidelines on epidemic prevention is found to be the most important and influential factor, which was followed by risk perception. Finally, attitude towards epidemic prevention exhibited the least degree of impact on individuals' intention to adopt epidemic prevention. Moral norms did not show any contribution to individuals’ intention to adopt epidemic prevention. Concerning importance ranking, the governments' guidelines on epidemic prevention, risk perception, and epidemic knowledge are revealed as the top three drivers of individuals' intention to adopt epidemic prevention, while the perceived feasibility to adopt epidemic prevention is found to be a barrier. Moreover, moral norms is identified to have an insignificant influence on individuals' intention to adopt epidemic prevention. Given the empirical results, dissemination of Governments’ guidelines on epidemic prevention, proper risk perception, and knowledge about epidemic would help prevent the COVID-19 pandemic outbreak within China and worldwide. • Examined perception-based influence factors of individuals' intention to adopt epidemic prevention. • Theory of planned behavior and theory of reasoned actions are modified to introduced new factors. • Governments' guidelines on epidemic prevention, risk perception, and epidemic knowledge are the top three drivers. • Perceived feasibility is revealed a barrier to adopt COVID-19 epidemic prevention. • Moral norms showed an insignificant role in adoption of COVID-19 epidemic prevention.

Devarbhavi H., Aithal G., Treeprasertsuk S., Takikawa H., Mao Y., Shasthry S.M., Hamid S., Tan S.S., Philips C.A., George J., Jafri W., Sarin S.K.

Idiosyncratic drug-induced liver injury mimics acute and chronic liver disease. It is under recognized and underrecognised because of the lack of pathognomonic diagnostic serological markers. Its consequences may vary from being asymptomatic to self-limiting illness to severe liver injury leading to acute liver failure. Its incidence is likely to be more common in Asia than other parts of the world, mainly because of hepatotoxicity resulting from the treatment of tuberculosis disease and the ubiquitous use of traditional and complimentary medicines in Asian countries. This APASL consensus guidelines on DILI is a concise account of the various aspects including current evidence-based information on DILI with special emphasis on DILI due to antituberculosis agents and traditional and complementary medicine use in Asia.

Salam R.A., Padhani Z.A., Das J.K., Shaikh A.Y., Hoodbhoy Z., Jeelani S.M., Lassi Z.S., Bhutta Z.A.

The objective of this review was to assess the impact of lifestyle interventions (including dietary interventions, physical activity, behavioral therapy, or any combination of these interventions) to prevent and manage childhood and adolescent obesity. We conducted a comprehensive literature search across various databases and grey literature without any restrictions on publication, language, or publication status until February 2020. We included randomized controlled trials and quasi-experimental studies from both high income countries (HIC) and low-middle-income countries (LMICs). Participants were children and adolescents from 0 to 19 years of age. Studies conducted among hospitalized children and children with any pre-existing health conditions were excluded from this review. A total of 654 studies (1160 papers) that met the inclusion criteria were included in this review. A total of 359 studies targeted obesity prevention, 280 studies targeted obesity management, while 15 studies targeted both prevention and management. The majority of the studies (81%) were conducted in HICs, 10% of studies were conducted in upper middle income countries, while only 2% of the studies were conducted in LMICs. The most common setting for these interventions were communities and school settings. Evidence for the prevention of obesity among children and adolescents suggests that a combination of diet and exercise might reduce the BMI z-score (MD: −0.12; 95% CI: −0.18 to −0.06; 32 studies; 33,039 participants; I2 93%; low quality evidence), body mass index (BMI) by 0.41 kg/m2 (MD: −0.41 kg/m2; 95% CI: −0.60 to −0.21; 35 studies; 47,499 participants; I2 98%; low quality evidence), and body weight (MD: −1.59; 95% CI: −2.95 to −0.23; 17 studies; 35,023 participants; I2 100%; low quality evidence). Behavioral therapy alone (MD: −0.07; 95% CI: −0.14 to −0.00; 19 studies; 8569 participants; I2 76%; low quality evidence) and a combination of exercise and behavioral therapy (MD: −0.08; 95% CI: −0.16 to −0.00; 9 studies; 7334 participants; I2 74%; low quality evidence) and diet in combination with exercise and behavioral therapy (MD: −0.13; 95% CI: −0.25 to −0.01; 5 studies; 1806 participants; I2 62%; low quality evidence) might reduce BMI z-score when compared to the control group. Evidence for obesity management suggests that exercise only interventions probably reduce BMI z-score (MD: −0.13; 95% CI: −0.20 to −0.06; 12 studies; 1084 participants; I2 0%; moderate quality evidence), and might reduce BMI (MD: −0.88; 95% CI: −1.265 to −0.50; 34 studies; 3846 participants; I2 72%) and body weight (MD: −3.01; 95% CI: −5.56 to −0.47; 16 studies; 1701 participants; I2 78%; low quality evidence) when compared to the control group. and the exercise along with behavioral therapy interventions (MD: −0.08; 95% CI: −0.16 to −0.00; 8 studies; 466 participants; I2 49%; moderate quality evidence), diet along with behavioral therapy interventions (MD: −0.16; 95% CI: −0.26 to −0.07; 4 studies; 329 participants; I2 0%; moderate quality evidence), and combination of diet, exercise and behavioral therapy (MD: −0.09; 95% CI: −0.14 to −0.05; 13 studies; 2995 participants; I2 12%; moderate quality evidence) also probably decreases BMI z-score when compared to the control group. The existing evidence is most favorable for a combination of interventions, such as diet along with exercise and exercise along with behavioral therapy for obesity prevention and exercise alone, diet along with exercise, diet along with behavioral therapy, and a combination of diet, exercise, and behavioral therapy for obesity management. Despite the growing obesity epidemic in LMICs, there is a significant dearth of obesity prevention and management studies from these regions.

Nobre L., Zapotocky M., Ramaswamy V., Ryall S., Bennett J., Alderete D., Balaguer Guill J., Baroni L., Bartels U., Bavle A., Bornhorst M., Boue D.R., Canete A., Chintagumpala M., Coven S.L., et. al.

PURPOSE Children with pediatric gliomas harboring a BRAF V600E mutation have poor outcomes with current chemoradiotherapy strategies. Our aim was to study the role of targeted BRAF inhibition in these tumors. PATIENTS AND METHODS We collected clinical, imaging, molecular, and outcome information from patients with BRAF V600E–mutated glioma treated with BRAF inhibition across 29 centers from multiple countries. RESULTS Sixty-seven patients were treated with BRAF inhibition (pediatric low-grade gliomas [PLGGs], n = 56; pediatric high-grade gliomas [PHGGs], n = 11) for up to 5.6 years. Objective responses were observed in 80% of PLGGs, compared with 28% observed with conventional chemotherapy ( P < .001). These responses were rapid (median, 4 months) and sustained in 86% of tumors up to 5 years while receiving therapy. After discontinuation of BRAF inhibition, 76.5% (13 of 17) of patients with PLGG experienced rapid progression (median, 2.3 months). However, upon rechallenge with BRAF inhibition, 90% achieved an objective response. Poor prognostic factors in conventional therapies, such as concomitant homozygous deletion of CDKN2A, were not associated with lack of response to BRAF inhibition. In contrast, only 36% of those with PHGG responded to BRAF inhibition, with all but one tumor progressing within 18 months. In PLGG, responses translated to 3-year progression-free survival of 49.6% (95% CI, 35.3% to 69.5%) versus 29.8% (95% CI, 20% to 44.4%) for BRAF inhibition versus chemotherapy, respectively ( P = .02). CONCLUSION Use of BRAF inhibition results in robust and durable responses in BRAF V600E–mutated PLGG. Prospective studies are required to determine long-term survival and functional outcomes with BRAF inhibitor therapy in childhood gliomas.