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COVID-19, a respiratory viral infection, has affected 388 million individuals worldwide as of the February 4, 2022. In this review, we have outlined the important liver manifestations of COVID-19 and discussed the possible underlying pathophysiological mechanisms and their diagnosis and management. Factors that may contribute to hepatic involvement in COVID-19 include direct viral cytopathic effects, exaggerated immune responses/systemic inflammatory response syndrome, hypoxia-induced changes, vascular changes due to coagulopathy, endothelitis, cardiac congestion from right heart failure, and drug-induced liver injury. The majority of COVID-19-associated liver symptoms are mild and self-limiting. Thus management is generally supportive. Liver function tests and abdominal imaging are the primary investigations done in relation to liver involvement in COVID-19 patients. However, imaging findings are nonspecific. Severe acute respiratory syndrome coronavirus 2 RNA has been found in liver biopsies. However, there is limited place for liver biopsy in the clinical context, as it does not influence management. Although, the management is supportive in the majority of patients without previous liver disease, special emphasis is needed in those with nonalcoholic fatty liver disease, cirrhosis, hepatocellular carcinoma, hepatitis B and C infections, and alcoholic liver disease, and in liver transplant recipients.

Background There is a paucity of predictive factors for early recovery from thrombocytopenia related to dengue. The immature platelet fraction (IPF%) is reflective of megakaryopoiesis and may correlate with recovery from dengue-related thrombocytopenia. Our objective was to assess the predictive value of IPF% on days 2 and 3 of illness for recovery from dengue-related thrombocytopenia. Methods A prospective study was conducted among patients with dengue admitted to our institution (Nawaloka Hospital PLC) from December 2019 to October 2020. Dengue was diagnosed based on positive non-structural antigen 1 or IgM. IPF% data were extracted from the Sysmex-XN-1000 automated hematology analyzer. Clinical data were obtained from electronic medical records. Statistical analyses were performed using SPSS version 20. Results We included 240 patients. An IPF% on day 2 of illness of >7.15% had a sensitivity of 80.0% and specificity of 70.4% for prediction of platelet recovery (defined as platelet count ≥60×109/L) on day 7 of illness. An IPF% of >7.25% on day 3 of illness had a sensitivity of 88.9% and specificity of 47.1% for predicting platelet recovery >60×109/L on day 8 of illness. The IPF% was significantly lower in patients with severe dengue. Platelet recovery was observed within 48 h after the peak IPF% was reached, regardless of severity. Conclusion We propose that IPF% values on days 2 and 3 of illness are a promising predictive tool for early recovery from dengue-related thrombocytopenia.

COVID-19 is caused by SARS-CoV-2. Although pulmonary manifestations have been identified as the major symptoms, several hematological abnormalities have also been identified. This review summarizes the reported hematological abnormalities (changes in platelet, white blood cell, and hemoglobin, and coagulation/fibrinolytic alterations), explores their patho-mechanisms, and discusses its management. Common hematological abnormalities in COVID-19 are lymphopenia, thrombocytopenia, and elevated D-dimer levels. These alterations are significantly more common/prominent in patients with severe COVID-19 disease, and thus may serve as a possible biomarker for those needing hospitalization and intensive care unit care. Close attention needs to be paid to coagulation abnormalities, and steps should be taken to prevent these occurring or to mitigate their harmful effects. The effect of COVID-19 in patients with hematological abnormalities and recognized hematological drug toxicities of therapies for COVID-19 are also outlined.

Star fruit (Averrhoa carambola), a popular fruit in many parts of the world, is considered to have many beneficial nutritional and medicinal effects. However, harmful nephrotoxic and neurotoxic effects have also been described. In this review, we have discussed the reported beneficial effects of star fruit, explored the potential mechanisms for such beneficial effects, and outline factors that may affect the safe level of consumption. The beneficial effects include the following: antioxidant (mediated via L‐ascorbic acid, epicatechin, and gallic acid), hypoglycemic (mediated via high fiber levels and 2‐dodecyl‐6‐methoxycyclohexa‐2,5‐diene‐1,4‐dione), hypotensive (mediated via apigenin), hypocholesterolemic (mediated via micronized fiber), anti‐inflammatory, anti‐infective, antitumor effects, and immune‐boosting effects. The presence of chronic kidney disease, gastroenteropathies, chronic pancreatitis, dehydration, consumption on an empty stomach, and higher concentration of oxalate in fruit/juice consumed predisposes to toxicity. The level of ingestion at which the beneficial effects transition to nephrotoxicity and neurotoxicity is still to be accurately ascertained. Furthermore, the relationship between the amount of star fruit ingested and the severity of toxicity is not certain and warrants further study., The nutritional and medical properties of star fruit include antioxidant, hypoglycemic, hypotensive, hypocholesterolemic, anti‐inflammatory, anti‐infective, and antitumor effects. However, majority of these findings are extrapolated from in vitro or animal studies. On the other hand, star fruit ingestion has also been shown to cause nephrotoxicity and neurotoxicity. Future studies should focus on the level of ingestion and conditions at which the beneficial effects become toxic.

Dengue infections are increasing globally and account for significant morbidity and mortality. Severe dengue results in microvascular changes and coagulopathy that may make surgical intervention risky and the overall surgical management challenging. We outline the potential surgical manifestations and complications following dengue infections and describe the clinical, pathogenetic, diagnostic, and treatment aspects of dengue and surgical patients. The main surgical presentations were acute cholecystitis, acute pancreatitis, acute appendicitis, splenic rupture, bowel perforation, gastrointestinal bleeding, and hematomas. Dengue may also mimic an acute abdomen without any true surgical complications. A majority were treated nonoperatively. Misdiagnosis and unnecessary surgical intervention resulted in poor outcomes. Better knowledge of the potential surgical complications would help in early diagnosis, treatment, and referral to specialized centers and thus improve outcomes. A high degree of suspicion of dengue fever is necessary when patients in a dengue-epidemic area present with acute abdomen or bleeding manifestations. In endemic areas, early dengue antigen testing and abdominal imaging before surgical intervention may help in the diagnoses. Multidisciplinary team involvement with case-by-case decision-making is needed for optimal care.

Objective: The aim of the study is to identify whether Atypical Lymphocyte (AL), liver transaminases, and Glutathione Reductase (GR) can be used as potential biomarkers in the assessment of severity and thrombocytopenia in dengue. Methods: A cross-sectional analytical study was carried out on diagnosed dengue patients admitted to Nawaloka Hospital, Sri Lanka. Blood samples were taken from patients (n = 50) on the day of admission, 3rd and 5th day from admission for analysis of GR, aspartate transaminase, alanine transaminase, platelets, white blood cells, and Atypical Lymphocytes (AL). Results: GR level of all three measured stages had a higher area under the curve (>88%), high sensitivity and specificity compared to liver transaminases. A significant regression model represents on admission GR and AL levels as predictive variables to platelet levels in day 03 from admission (Day 3 Platelet level = 127155.3 - 383 * GR - 0.431 * AL). Conclusion: Liver transaminases, GR, and AL% can be considered as a profile of predictive biomarkers in early diagnosis of severity of dengue infection. The degree of thrombocytopenia can be predicted using on admission GR and AL% level in acute dengue viral infection.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected over 220 million individuals worldwide, and has been shown to cause increased disease severity and mortality in patients with active cancer versus healthy individuals. Vaccination is important in reducing COVID-19-associated morbidity and mortality. Thus, the aim of this article was to review the existing knowledge on effectiveness, immunogenicity and safety of COVID-19 vaccines in patients with cancer. Fifty-four articles were included following a search of PubMed and Google Scholar databases for studies published between January 2020 and September 2021 that investigated humoral and cell-mediated immune responses following COVID-19 vaccination in patients with cancer. Immunogenicity of vaccines was found to be lower in patients with cancer versus healthy individuals, and humoral immune responses were inferior in those with haematological versus solid cancers. Patient-, disease-, and treatment-related factors associated with poorer vaccine responses should be identified and corrected or mitigated when possible. Consideration should be given to offering patients with cancer second doses of COVID vaccine at shorter intervals than in healthy individuals. Patients with cancer warrant a third vaccine dose and must be prioritized in vaccination schedules. Vaccine adverse effect profiles are comparable between patients with cancer and healthy individuals.

Dengue is an important global health problem and is endemic in many developing and developed countries. Transmission of dengue may occur in several ways and information on transfusion-transmitted dengue is limited. We conducted a literature search on transfusion-related dengue using the PubMed, Scopus, Embase and Google Scholar databases and have summarized the findings. A number of apparently healthy blood donors have been found to be infected with the dengue virus (DENV) and thus may transmit the virus onto recipients of this blood. It is not possible to identify and exclude such donors at the donor selection stage and thus reliable screening tests should be available in highly endemic areas to ensure a safe blood supply.

Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, emerged in Wuhan, China in December 2019. It has now spread to all parts of the world and as of 26th July 2020, more than 16 million cases and over 600,000 deaths have been reported. The commonest presentation is respiratory in nature with non-productive cough, fever and shortness of breath. Some COVID-19 patients have had atypical or unusual presentations involving the neurological, metabolic, gastrointestinal, renal, haematological, cutaneous and cardiovascular systems. In this mini-review, we have outlined the main atypical or unusual clinical presentations of COVID-19.

Background: the heterogeneity and lack of validation of existing severity scores for food allergic reactions limit standardization of case management and research advances. We aimed to develop and validate a severity score for food allergic reactions. Methods: following a multidisciplinary experts consensus, it was decided to develop a food allergy severity score (FASS) with ordinal (oFASS) and numerical (nFASS) formats. oFASS with 3 and 5 grades were generated through expert consensus, and nFASS by mathematical modeling. Evaluation was performed in the EuroPrevall outpatient clinic cohort (8232 food reactions) by logistic regression with request of emergency care and medications used as outcomes. Discrimination, classification, and calibration were calculated. Bootstrapping internal validation was followed by external validation (logistic regression) in 5 cohorts (3622 food reactions). Correlation of nFASS with the severity classification done by expert allergy clinicians by Best-Worst Scaling of 32 food reactions was calculated. Results: oFASS and nFASS map consistently, with nFASS having greater granularity. With the outcomes emergency care, adrenaline and critical medical treatment, oFASS and nFASS had a good discrimination (receiver operating characteristic area under the curve [ROC-AUC]>0.80), classification (sensitivity 0.87–0.92, specificity 0.73–0.78), and calibration. Bootstrapping over ROC-AUC showed negligible biases (1.0 × 10 −6–1.23 × 10 −3). In external validation, nFASS performed best with higher ROC-AUC. nFASS was strongly correlated (R 0.89) to best-worst scoring of 334 expert clinicians. Conclusion: FASS is a validated and reliable method to measure severity of food allergic reactions. The ordinal and numerical versions that map onto each other are suitable for use by different stakeholders in different settings.

Hyper-IgE syndromes and chronic mucocutaneous candidiasis constitute rare primary immunodeficiency syndromes with an overlapping clinical phenotype. In recent years, a growing number of underlying genetic defects have been identified. To characterize the underlying genetic defects in a large international cohort of 275 patients, of whom 211 had been clinically diagnosed with hyper-IgE syndrome and 64 with chronic mucocutaneous candidiasis, targeted panel sequencing was performed, relying on Agilent HaloPlex and Illumina MiSeq technologies. The targeted panel sequencing approach allowed us to identify 87 (32 novel and 55 previously described) mutations in 78 patients, which generated a diagnostic success rate of 28.4%. Specifically, mutations in DOCK8 (26 patients), STAT3 (21), STAT1 (15), CARD9 (6), AIRE (3), IL17RA (2), SPINK5 (3), ZNF341 (2), CARMIL2/RLTPR (1), IL12RB1 (1), and WAS (1) have been detected. The most common clinical findings in this cohort were elevated IgE (81.5%), eczema (71.7%), and eosinophilia (62.9%). Regarding infections, 54.7% of patients had a history of radiologically proven pneumonia, and 28.3% have had other serious infections. History of fungal infection was noted in 53% of cases and skin abscesses in 52.9%. Skeletal or dental abnormalities were observed in 46.2% of patients with a characteristic face being the most commonly reported feature (23.1%), followed by retained primary teeth in 18.9% of patients. Targeted panel sequencing provides a cost-effective first-line genetic screening method which allows for the identification of mutations also in patients with atypical clinical presentations and should be routinely implemented in referral centers., Projekt DEAL; German Ministry of Education and Research (BMBF) [01E01303, 01ZX1306F, 01ZX1306A]; E-rare program of the European Commission EURO-CMC [01GM1502]; German Center for Infection Research DZIF [8000805-3, TTU-IICH_07.801]; German Research Foundation (DFG) [390939984, 39087428], Open Access funding enabled and organized by Projekt DEAL. Financial support for this research came from the German Ministry of Education and Research (BMBF, grant no. 01E01303; sys-INFLAME grant nos. 01ZX1306F and 01ZX1306A), from the E-rare program of the European Commission EURO-CMC (01GM1502), and from the German Center for Infection Research DZIF (8000805-3 and TTU-IICH_07.801). This study was supported by the German Research Foundation (DFG) under Germany's Excellence Strategy CIBSS (EXC-2189) (Project ID 390939984) and RESIST (EXC 2155) (Project ID 39087428).

Background Coronavirus disease 2019 (COVID-19) may cause clinical manifestations that last for weeks or months after hospital discharge. The manifestations are heterogeneous and vary in their frequency. Their multisystem nature requires a holistic approach to management. There are sparse data from the South Asian region on the outcomes of hospital-discharged COVID-19 patients. We assessed the posthospital discharge outcomes of a cohort of Sri Lankan COVID-19 patients and explored the factors that influenced these outcomes. Methods Data were prospectively collected from patients who were discharged following an admission to the Nawaloka Hospital, Sri Lanka with COVID-19 from March to June 2021. At discharge, their demographic, clinical and laboratory findings were recorded. The patients were categorised as having mild, moderate and severe COVID-19, based on the Sri Lanka Ministry of Health COVID-19 guidelines. Following discharge, information on health status, complications and outcomes was collected through clinic visits and preplanned telephone interviews. A validated (in Sri Lanka) version of the Short Form 36 health survey questionnaire (SF-36) was used to assess multi-item dimensions health status of the patients at 1, 2 and 3 mo postdischarge. Results We collected data on 203 patients (male, n=111 [54.7%]). The level of vaccination was significantly associated with disease severity (p Conclusions In our cohort, receiving two doses of the COVID-19 vaccine was associated with reduced disease severity. Those with mild disease recovered faster than those with moderate/severe disease. At 3 mo posthospital discharge, >90% had recovered.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, has currently affected >220 million individuals worldwide. The complex interplay of immune dysfunction, active malignancy, the effect of cancer treatment on the immune system and additional comorbidities associated with cancer and COVID-19 all affect the outcomes of COVID-19 in patients with cancer. We have discussed the published findings (through the end of September 2021) on the effects of cancer on the morbidity and mortality of COVID-19, common factors between cancer and COVID-19, the interaction of cancer and COVID-19 treatments, the impact of COVID-19 on cancer clinical services, immune test findings in cancer patients with COVID-19 and the long-term effects of COVID-19 on cancer survivors.

Background There is currently no clinically validated biomarker to predict respiratory compromise in sudden acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Cycle threshold time (Ct), absolute lymphocyte count (AL) and neutrophil:lymphocyte ratio (NLR) have been previously evaluated for this purpose. We hypothesized that the combination of these parameters at presentation may be predictive of hypoxia (oxygen saturation Methods Data were collected on 118 patients with SARS-CoV-2 infection between May 2020 and April 2021. Demographics, clinical parameters and laboratory and radiological investigation results were recorded. Respiratory compromise (RC) was defined based on symptoms and signs, hypoxia and chest X-ray abnormalities. Results RC occurred in 61 (51.7%) of patients. The Ct, AL and NLR at median day 3 of illness were significantly different between patients with and without RC (Ct, RC vs not: 19.46±2.64 vs 22.62±3.37, p=0.0001; AL, RC vs not: 531.49±289.09 vs 764.69±481.79, p=0.0001; NLR, RC vs not: 3.42±0.75 vs 2.59±0.55, p=0.0001). Receiver operating characteristics analysis showed that a Ct 3.12 at median day 3 of symptoms was predictive of hypoxia on day 7 of illness (area under the curve 0.805, sensitivity 96.7%, specificity 69.1%). The predictive value for the parameters combined was significantly superior to their individual predictive power. Conclusions Ct, AL and NLR used in combination on day 3 of symptoms are predictive of hypoxia on day 7 of SARS-CoV-2 illness.

Background The role of steroids in dengue infection (DI) remains uncertain. Methods A retrospective chart review was conducted on patients ≥18 y of age diagnosed with DI based on positivity for dengue non-structural antigen 1 or immunoglobulin M between October 2017 and November 2018. Results Hydrocortisone was administered to 106 of 406 patients. DI with warning signs occurred in nine patients (9.5%) in the steroid cohort and eight patients (2.5%) in the non-steroid group. The incidence of severe DI, bleeding and admission duration were similar between the groups. Conclusions Our study shows no significant benefit of empirical steroids in DI.

Identification of redox markers may be of clinical significance in the management of dengue patients. This study is to identify the association between antioxidant enzymes, hematological parameters and liver transaminases in patients with acute dengue infection. Blood samples were taken from patients on the day of admission, day 05 and 07 from admission for analysis of glutathione peroxidase (GPX), glutathione reductase (GR), aspartate transaminase (AST), alanine transaminase (ALT) and hematological parameters. AST and ALT levels were significantly elevated (p < 0.05) on day 05 in dengue patients. In contrast, GPX and GR showed significantly low levels on day 05 compared to on the day of admission and day 07. Although there was a decline in the trend of platelets towards day 05, values were not significantly different. Dengue associated with liver injury appears to peak around day 05 when the GPX and GR enzymes levels in patients were the lowest suggesting that increased viral load in the acute phase of dengue infection has initiated an antioxidant imbalance. Thus, timely investigation of antioxidant enzymes (GR and GPX) and liver transaminases around day 05 of admission may be of value in the management of patients with dengue infection similar to as seen in platelet counts.

Coronavirus disease 2019 (COVID-19), a respiratory viral infection, has affected more than 78 million individuals worldwide as of the end of December 2020. Previous studies reported that severe acute respiratory syndrome coronavirus 1 and Middle East respiratory syndrome–related coronavirus infections may affect the gastrointestinal (GI) system. In this review we outline the important GI manifestations of COVID-19 and discuss the possible underlying pathophysiological mechanisms and their diagnosis and management. GI manifestations are reported in 11.4–61.1% of individuals with COVID-19, with variable onset and severity. The majority of COVID-19-associated GI symptoms are mild and self-limiting and include anorexia, diarrhoea, nausea, vomiting and abdominal pain/discomfort. A minority of patients present with an acute abdomen with aetiologies such as acute pancreatitis, acute appendicitis, intestinal obstruction, bowel ischaemia, haemoperitoneum or abdominal compartment syndrome. Severe acute respiratory syndrome coronavirus 2 RNA has been found in biopsies from all parts of the alimentary canal. Involvement of the GI tract may be due to direct viral injury and/or an inflammatory immune response and may lead to malabsorption, an imbalance in intestinal secretions and gut mucosal integrity and activation of the enteric nervous system. Supportive and symptomatic care is the mainstay of therapy. However, a minority may require surgical or endoscopic treatment for acute abdomen and GI bleeding.

ObjectiveWe aimed to describe the clinical characteristics of chronic pancreatitis (CP) and patient quality of life (QOL) in a resource-limited setting.MethodsWe performed a cross-sectional study including patients with clinical and radiological features of CP. We collected clinical data and assessed QOL using the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire.ResultsWe included 103 patients (median age 44 years, 84 men). Median age at symptom onset was 36 (4–78) years. Around 70% of patients had diabetes mellitus and 62.1% had consumed alcohol; 36 (35%) were current smokers. The mean overall global QOL score was 68.7. Most patients (91.3%) sought treatment from multiple centers. Nineteen (18.5%) had pancreatic stone disease, 38 (36.9%) had persistent abdominal pain (median severity 7.8/10, 59 (57.3%) had steatorrhea, and 56 (54.4%) had jaundice. Poor QOL was significantly associated with weight loss, loss of appetite, and intractable pain. No correlation with age, sex, or alcohol consumption was noted.ConclusionA considerable proportion of patients with CP had troublesome symptoms. Intractable pain, loss of appetite, and weight loss were significantly associated with poor QOL. Further assessment is needed of patients’ psychosocial well-being and its association with QOL.

Background Ultrasound (US) is an investigation available in many acute care settings. Thrombocytopenia is a well-described complication of dengue infection and has been shown to correlate with disease severity. The purpose of this study was to assess the utility of admission ultrasonography in predicting thrombocytopenia and disease severity in patients infected with dengue virus. Methods Data were collected prospectively on 176 patients (male, n=86; female, n=90) admitted to the Nawaloka Hospital, Sri Lanka with dengue infection between December 2016 and August 2018. All patients had an US scan on admission and disease severity was determined using the World Health Organization 2009 classification. Results There were 106 (60.2%) cases of dengue with/without warning signs and 70 (39.8%) cases of severe dengue. Patients with an abnormal US on admission were more likely to have severe dengue. Gallbladder wall thickening was the most common US abnormality. Abnormal US findings significantly correlated with more pronounced thrombocytopenia from day 2 of admission. Conclusions An abnormal US scan on admission can aid in identification of patients at risk of developing severe dengue and can be used as a novel clinical tool to identify patients at risk of severe thrombocytopenia.

Introduction: Analyzing dengue disease patterns from different parts of the world should help us formulate more evidence based treatment guidelines and appropriately allocate limited healthcare resources. Therefore, we described the disease characteristics of hospitalised pediatric patients with dengue infections from Sri Lanka during the 2017 dengue epidemic. Methods: Clinical and biochemical characteristics of pediatric dengue patients treated at a secondary care hospital in Sri Lanka from 1 June 2017 to 31 August 2017 were analyzed. Our findings were compared with previous pediatric dengue studies in Asia. Results: A total of 305 patients (number of males = 184(60%); mean age = 8.6 years) were analyzed. DF (Dengue Fever)—245 (80.3%), DHF (Dengue Hemorrhagic fever)—I:52 (17%), DHF—II:7 (2.3%), and DHF—III:1 (0.3%). Significant associations were found between DHF and abdominal symptoms/signs and overt bleeding manifestations ( P Conclusion: In Sri Lankan pediatric dengue patients, we found abdominal symptoms and signs, decreased WBC and platelet counts and bleeding manifestations were to be significantly associated with DHF. Liver enzyme derangement did not predict DHF. The time of onset of the critical phase was difficult to predict due to the considerable variations noted.

In recent times, star fruit (Averrhoa carambola) nephrotoxicity and neurotoxicity have been increasingly reported, both in individuals with pre-existing renal disease and those with previously normal renal function. We summarise the clinical findings of star fruit toxicity in humans and outline the important pathogenetic insights provided by animal studies. Google Scholar, EMBASE, Scopus and PubMed were searched from 1995 through July 2020 for case reports/series on renal or neurological manifestations of star fruit toxicity in humans and mechanisms of star fruit toxicity in animal studies. Ten case series and 28 case reports in humans (total number of individuals=136) were included and 8 animal studies were analysed. Ninety-four (69.1%) patients had prior renal impairment. Renal histology showed acute oxalate nephropathy with tubulointerstitial nephritis or tubular necrosis. Neurotoxicity manifestations ranged from hiccups to status epilepticus. Oxalate and caramboxin are considered the main substances causing nephrotoxicity and neurotoxicity. Caramboxin inhibits GABA binding and activates the glutamatergic receptors. Haemodialysis improved outcomes in neurotoxicity. Nephrotoxicity and neurotoxicity need to be looked for with star fruit toxicity, both in individuals with abnormal or normal renal function. Once star fruit intoxication is identified, early renal replacement therapy should be considered. Further studies on the mechanisms of star fruit toxicity are needed.

COVID-19, a respiratory viral infection, has affected more than 10 million individuals worldwide. Common symptoms include fever, dry cough, fatigue and shortness of breath. Some patients show neurological manifestations such as headache, dizziness, cerebrovascular disease, peripheral nerve and muscle symptoms and smell and taste impairment. In previous studies, SARS-CoV-1 and MERS-CoV were found to affect the nervous system. Given the high similarity between SARS-CoV-1 and SARS-CoV-2, effects on the nervous system by SARS-CoV-2 are a possibility. We have outlined the common neurological manifestations in COVID-19 (information are up-to-date as of June 2020) and discussed the possible pathogenetic mechanisms and management options.

The SARS-CoV-2 virus was first encountered in Wuhan, China in December 2019. At the present time, coronavirus disease 2019 (Covid-19) affects more than 170 countries. Several groups are carrying out intense research on drugs and vaccines to treat or prevent Covid-19. We have outlined aspects relating to Remdesivir, in treating RNA viral infections and its potential role in controlling SARS-Cov-2 infections.

Introduction: Due to the shortcomings in the 1997-World Health Organisation (WHO) dengue case classification (DCC), a revised classification was proposed in 2009. This study was aimed to assess the clinical usefulness of the two classifications during a large dengue epidemic. Methodology: Clinical data of dengue patients admitted to selected units at National Hospital of Sri Lanka, Panadura Base Hospital and Nawaloka Hospital Colombo between June and August 2017 were collected prospectively. Cases were classified using the 1997 and 2009 WHO DCCs. Results: 1,878 patients [adult = 1,573 (83.8%)] were studied. Based on 1997-WHO-DCC-DF (Dengue Fever): 1,316 (70.1%), DHF (Dengue Haemorrhagic Fever) -1: 468 (24.9%), DHF-2: 86 (4.6%) and DHF-3: 8 (0.4%). Based on 2009-WHO-DCC–Dengue with warning signs (WS): 1647 (87.7%), Dengue without WS: 231 (12.3%) and severe dengue (SD): 41 (2.18%). A total of 1,088 (82.7%) DF and 559 (99.5%) DHF patients developed WS. Of those without WS, 228 (17.3%) were DF patients and 3 (0.5%) were DHF patients. Three (0.23%) DF and 38 (6.76%) DHF patients had SD. All SD patients had WS. The level of agreement between the two systems of classification was poor (Kappa = - 0.035, p < 0.001). Conclusions: The 2009-WHO-DCC was more useful than 1997-WHO-DCC in predicting dengue disease severity as few DF patients also had SD. Furthermore, the presence of WS identified patients with SD. However, the 2009-WHO-DCC may not suit the resource limited countries as WS are non-specific, and lack of diagnostic tests can result in case overload.

BACKGROUND: Walnut allergy is common across the globe, but data on the involvement of individual walnut components are scarce.OBJECTIVES: To identify geographical differences in walnut component sensitization across Europe, explore cosensitization and cross-reactivity, and assess associations of clinical and serological determinants with severity of walnut allergy.METHODS: As part of the EuroPrevall outpatient surveys in 12 European cities, standardized clinical evaluation was conducted in 531 individuals reporting symptoms to walnut, with sensitization to all known walnut components assessed in 202 subjects. Multivariable Lasso regression was applied to investigate predictors for walnut allergy severity.RESULTS: Birch-pollen-related walnut sensitization (Jug r 5) dominated in Northern and Central Europe and lipid transfer protein sensitization (Jug r 3) in Southern Europe. Profilin sensitization (Jug r 7) was prominent throughout Europe. Sensitization to storage proteins (Jug r 1, 2, 4, and 6) was detected in up to 10% of subjects. The walnut components that showed strong correlations with pollen and other foods differed between centers. The combination of determinants best predicting walnut allergy severity were symptoms upon skin contact with walnut, atopic dermatitis (ever), family history of atopic disease, mugwort pollen allergy, sensitization to cat or dog, positive skin prick test result to walnut, and IgE to Jug r 1, 5, 7, or carbohydrate determinants (area under the curve = 0.81; 95% CI, 0.73-0.89).CONCLUSIONS: Walnut-allergic subjects across Europe show clear geographical differences in walnut component sensitization and cosensitization patterns. A predictive model combining results from component-based serology testing with results from extract-based testing and information on clinical background allows for good discrimination between mild to moderate and severe walnut allergy.

Contains fulltext : 229571.pdf (Publisher’s version ) (Closed access) BACKGROUND: An increasing number of NFKB1 variants are being identified in patients with heterogeneous immunologic phenotypes. OBJECTIVE: To characterize the clinical and cellular phenotype as well as the management of patients with heterozygous NFKB1 mutations. METHODS: In a worldwide collaborative effort, we evaluated 231 individuals harboring 105 distinct heterozygous NFKB1 variants. To provide evidence for pathogenicity, each variant was assessed in silico; in addition, 32 variants were assessed by functional in vitro testing of nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-κB) signaling. RESULTS: We classified 56 of the 105 distinct NFKB1 variants in 157 individuals from 68 unrelated families as pathogenic. Incomplete clinical penetrance (70%) and age-dependent severity of NFKB1-related phenotypes were observed. The phenotype included hypogammaglobulinemia (88.9%), reduced switched memory B cells (60.3%), and respiratory (83%) and gastrointestinal (28.6%) infections, thus characterizing the disorder as primary immunodeficiency. However, the high frequency of autoimmunity (57.4%), lymphoproliferation (52.4%), noninfectious enteropathy (23.1%), opportunistic infections (15.7%), autoinflammation (29.6%), and malignancy (16.8%) identified NF-κB1-related disease as an inborn error of immunity with immune dysregulation, rather than a mere primary immunodeficiency. Current treatment includes immunoglobulin replacement and immunosuppressive agents. CONCLUSIONS: We present a comprehensive clinical overview of the NF-κB1-related phenotype, which includes immunodeficiency, autoimmunity, autoinflammation, and cancer. Because of its multisystem involvement, clinicians from each and every medical discipline need to be made aware of this autosomal-dominant disease. Hematopoietic stem cell transplantation and NF-κB1 pathway-targeted therapeutic strategies should be considered in the future.

Supplemental material, sj-pdf-1-gph-10.1177_2333794X20974207 for Clinical and Biochemical Characteristics of Dengue Infections in Children From Sri Lanka by Umesh Jayarajah, Manohari Madarasinghe, Damayanthi Hapugoda, Upul Dissanayake, Lakshika Perera, Vibhavee Kannangara, Champika Udayangani, Ranga Peiris, Pamodh Yasawardene, Ishan De Zoysa and Suranjith L. Seneviratne in Global Pediatric Health

Additional file 1: Figure S1. Questionnaire on Imaging in Rectal Cancer – questionnaire aimed at gathering information on the imaging modalities used by Sri – Lankan surgeons for rectal cancer patients.

Background Hyper IgE recurrent infection syndrome (HIES) is a rare immune deficiency, characterized by recurrent staphylococcal skin and lung abscesses, pneumonia and increased IgE levels. The majority of autosomal dominant HIES (AD HIGE) is due to hypomorphic mutations in the signal transducer and the activator of transcription 3 (STAT3) gene. Case presentation Five patients were diagnosed with HIES, based on the clinical criteria and scoring system developed at the National Institutes of Health (NIH), USA. The STAT3 gene was sequenced and previously described mutations were identified in all five patients. We compare the clinical features of our patients with those from Asia, Europe and the US. Conclusion Even though the number of patients is limited, there are some clinical differences in patients from South Asia compared to European and even East Asian patients. However, the mutations detected are located at hot spots seen in western and Asian patients with AD HIGE.

Background Allergy to Vespa affinis venom is common in the Asia Pacific region. Venom preparations for diagnosis are not commercially available for this species. Methods The prominent allergens in V. affinis venom were identifiedusing immunochemical methods. Use of ImmunoCAP of Vespula vulgaris crude venom/its components and a passive basophil activation test (BAT) in the diagnosis of patients who had anaphylaxis to V. affinis venom (n = 30) were also accessed. The IgE double-positivity rates (positive to both hornet and honeybee) in ImmunoCAP and the passive BAT were determined. Results High IgE reactivity was seen with the five allergens in V. affinis venom; 96% (29/30) for 34 and 24 kDa, 93% (28/30) for 45 kDa and 90% (27/30) reactivity for the 100 and 80 kDa respectively. IgE cross-reactivity was low with ImmunoCAP using V. vulgaris venom (43%; 13/30) and Ves v1 (3%; 1/30), but relatively high with Ves v5 (73%; 22/30). All patients (100%) were positive to V. affinis venom in passive BAT. In ImmunoCAP, a high double-positivity rate (76%; 23/30) was detected while no double-positivity was detected in passive BAT. Conclusions High IgE reactivity for five allergens of V. affinis points to the potential of using these allergens in component resolved diagnosis (CRD). The passive BAT has shown its importance as a promising diagnostic tool with high accuracy. It would be particularly useful in cases with doubtful double-positive results of other diagnostic tests.

Objectives There has been a global increase in the incidence and prevalence of NAFLD. We assessed the knowledge and awareness of NAFLD among gastroenterology doctors in three state sector hospitals. Results 80 medical officers and 58 post-graduate trainee doctors/consultants responded. 110 (79.7%) considered NAFLD a major health problem whilst 97 (70.3%) thought the prevalence of NAFLD was 10–40%. 52.9% saw 12–24 patients with NAFLD/year. A vast majority knew the risk factors for NAFLD: 127 (92.7%) diabetes mellitus, 135 (97.8%) Obesity, 132 (95.7%) Dyslipidemia and 87 (63%) PCOS. The methods for diagnosis were recognized by: USS 132 (95.7%), MRI 34 (24.6%), transient elastography 23 (16.7%) and liver biopsy 88 (63.8%) while, 53 (38.4%) recognized the non-invasive methods available for diagnosis. The trends in referral were lower than expected: 85 (61.6%) refer to a Gastroenterologist/Physician, 53 (38.4%) to a Gym, 67 (48.6%) to a weight loss clinic and 45 (32.6%) to a dietician. Significantly more postgraduate trainee doctors: recognized the availability of non-invasive investigations for NAFLD (P = 0.01) and read guidelines on NAFLD (P = 0.02) compared to non-trainee doctors. As a whole, a majority (57.2%) had not attended a lecture or read a guideline on NAFLD. The barriers for management included: lack of confidence 70 (50.7%) and time constraints 58 (42%). Electronic supplementary material The online version of this article (10.1186/s13104-018-3673-2) contains supplementary material, which is available to authorized users.

Background The standard dose of rituximab used in rheumatoid arthritis (RA) is 1000 mg but recent studies have shown that low dose (500 mg) is also effective. Efficacy of low dose rituximab in rheumatoid arthritis (RA) refractory to first-line non-biologic Disease Modifying Anti Rheumatic Drugs (DMARDs), compared to leflunomide is unknown. In a tertiary care referral setting, we conducted a randomized, double blind controlled clinical trial comparing the efficacy and safety of low-dose rituximab-methotrexate combination with leflunomide-methotrexate combination. Methods Patients on methotrexate (10-20 mg/week) with a Disease Activity Score (DAS) > 3.2 were randomly assigned to rituximab (500 mg on days 1 and 15) or leflunomide (10-20 mg/day). The primary end-point was ACR20 at 24 weeks. Sample of 40 had 70% power to detect a 30% difference. ACR50, ACR70, DAS, EULAR good response, CD3 + (T cell), CD19 + (B cell) and CD19 + CD27+ (memory B cell) counts, tetanus and pneumococcal antibody levels were secondary end points. Results Baseline characteristics were comparable in the two groups. At week 24, ACR20 was 85% vs 84% (p = 0.93), ACR50 was 60% vs. 64% (p = 0.79) and ACR70 was 35% vs 32% (P = 0.84), in rituximab and in leflunomide groups respectively. Serious adverse events were similar. With rituximab there was significant reduction in B cells (p 0.05), T cells (P > 0.05) or tetanus antibody levels (P > 0.05). Conclusions Leflunomide-methotrexate combination is as efficacious as low-dose rituximab-methotrexate combination at 24 weeks, in RA patient’s refractory to initial DMARDs. The high responses seen in both groups have favorable cost implications for patients in developing countries. Changes in immune parameters with leflunomide are novel and need further characterization. Trial registration The trial was registered with the Sri Lanka Clinical Trials Registry (SLCTR), a publicly accessible primary registry linked to the registry network of the International Clinical Trials Registry Platform of the WHO (WHO-ICTRP) (registration number: SLCTR/2008/008 dated 16th May 2008).