Lower White Cell Count Research Articles

Autopsy findings from patients diagnosed with COVID-19 demonstrate unique morphological patterns in bone marrow and lymph node

AimsThe identification of haemophagocytosis in bone marrow (BM) is recurrently identified in patients with severe COVID-19. These initial COVID-19 autopsy studies have afforded valuable insight into the pathophysiology of this...

Predictive value of pretreatment circulating inflammatory response markers in the neoadjuvant treatment of breast cancer: meta-analysis.

Systemic inflammatory response markers have been found to have a prognostic role in several cancers, but their value in predicting the response to neoadjuvant chemotherapy in breast cancer is uncertain. A systematic review and meta-analysis of the literature was carried out to investigate this. A systematic search of electronic databases was conducted to identify studies that explored the predictive value of circulating systemic inflammatory response markers in patients with breast cancer before commencing neoadjuvant therapy. A meta-analysis was undertaken for each inflammatory marker where three or more studies reported pCR rates in relation to the inflammatory marker. Outcome data are reported as ORs and 95% confidence intervals. A total of 49 studies were included, of which 42 were suitable for meta-analysis. A lower pretreatment neutrophil-to-lymphocyte ratio was associated with an increased pCR rate (pooled OR 1.66 (95% c.i. 1.32 to 2.09); P < 0.001). A lower white cell count (OR 1.96 (95% c.i. 1.29 to 2.97); P = 0.002) and a lower monocyte count (OR 3.20 (95% c.i. 1.71 to 5.97); P < 0.001) were also associated with a pCR. A higher lymphocyte count was associated with an increased pCR rate (OR 0.44 (95% c.i. 0.30 to 0.64); P < 0.001). The present study found the pretreatment neutrophil-to-lymphocyte ratio, white cell count, lymphocyte count, and monocyte count of value in the prediction of a pCR in the neoadjuvant treatment of breast cancer. Further research is required to determine their value in specific breast cancer subtypes and to establish optimal cut-off values, before their adoption in clinical practice.

O184: Predictive value of pre-treatment circulating inflammatory response markers in the neoadjuvant treatment of breast cancer: a systematic review and meta-analysis

Abstract Purpose Systemic inflammatory response markers have been found to have a prognostic role in several cancers, but their value in predicting response to neoadjuvant chemotherapy is uncertain. A systematic review and meta-analysis of the literature was carried out to investigate this. Methods A systematic search of electronic databases was conducted to identify studies that explored the predictive value of circulating systemic inflammatory response markers in patients with breast cancer prior to commencing neoadjuvant therapy. A meta-analysis was undertaken for each inflammatory marker where three or more studies reported pathological complete response (pCR) rates in relation to the inflammatory marker. Outcome data were reported as odds ratios (ORs) using 95% confidence intervals (CIs). Results Forty-nine studies were included in total, of which 42 were suitable for meta-analysis. Lower pre-treatment neutrophil-lymphocyte-ratio (NLR) was associated with an increased rate of pCR (pooled OR 1.66, 95% CI 1.32 to 2.09; P&amp;lt;0.001). Lower white cell count (WCC) (OR 1.96, 95% CI 1.29 to 2.97, P=0.002) and lower monocyte count (OR 3.20, 95% CI 1.71 to 5.97) were also associated with pCR. Higher lymphocyte count was associated with increased pCR rate (OR 0.44, 95% CI 0.30 to 0.64, P&amp;lt;0.0001). Conclusion The present study found pre-treatment NLR, WCC, lymphocyte count and monocyte count of value in the prediction of pCR in the neoadjuvant treatment of breast cancer. However, further research is required to determine their value in specific breast cancer subtypes and to establish optimal cut-off values, prior to their adoption in clinical practice.

Cerebral Toxoplasmosis in an Immunocompetent Patient With Confirmed Covid-19 Positive

A case of a 30 years-old male patient, diagnosed with cerebral toxoplasmosis, confirmed HIV, with positive COVID-19. Once he came to the emergency department with a chief complaint of left upper and lower limbs weakness progressing for two days. The patient appeared malnourished and was afebrile and assessed to be well hydrated. He was alert but drowsy and had speech difficulty. A focused neurologic examination was performed and revealed a loss of nasolabial fold indicating facial nerve palsy. Neck stiffness was present and there was reduced motoric power in the left upper and lower limb of 2/5, with positive Babinski sign and Chaddock sign. According to brain CT, showed vasogenic cerebral edema and midline shift. Further laboratory exams showed positive IgG antibodies for Toxoplasma, with a titer exceeding 300 IU/ml, positive serum HIV, with CD4 cell count below 200cell/mm3. Complete blood count study highlighted low haemoglobin and elevated white cell count. He tested positive for COVID-19 by nasopharyngeal swab RT-PCR. Chest CT were done and revealed features of viral pneumonia with ground glass opacity appearance. In summary, we present a patient with cerebral involvement of toxoplasmosis possibly facilitated by pre-existing immunodeficiency as an opportunistic infections of HIV, and with COVID-19 complicated as acute infections. This case report reinforces a potential role for other comorbidities, rather than HIV infection as regards SARS-CoV-2 infection outcomes. For better assessment we need to do MRI.

Clinicoetiological profile of children with bicytopenia and pancytopenia

BackgroundBicytopenia, and pancytopenia have a wide etiological spectrum in children, ranging from viral infections to malignancies. There is limited data describing the clinicoetiological profile of bicytopenia and pancytopenia in children in recent times. MethodologyFifty children, aged 1 month to 12 years admitted with bicytopenia and pancytopenia were enrolled and evaluated. Basic patient information and clinical findings along with relevant investigations were obtained on a predesigned proforma and analyzed statistically. ResultsAmong the 50 cases studied, 46 had non-malignant causes, 24 (92.3%) cases had bicytopenia and 22 (91.66%) had pancytopenia. Among the 46 cases, 20 were infectious in origin. Sepsis was the commonest cause comprising 7 out of 20 cases (35%). Other causes included dengue fever, enteric fever, and malaria. The commonest cause of bicytopenia was nutritional anemia, observed in 8 out of 15 (53%) cases. The common causes of pancytopenia were megaloblastic anemia and aplastic anemia. Hematological parameters were significantly different among the bicytopenic and pancytopenic groups. MCH and MCHC were not significantly different between the groups. Hemoglobin and low white cell count were observed in aplastic anemia while thrombocytopenia was more marked in patients with megaloblastic anemia. A diagnosis of leukemia was made in 4 out of 50 cases, of which 2 each had pancytopenia and bicytopenia at presentation. ConclusionThe common causes of bicytopenia and pancytopenia were infections and nutritional deficiency. A history, examination and basic diagnostic tests were rewarding for the diagnosis in the majority.

Use of non-selective B-blockers is safe in hospitalised decompensated cirrhosis patients and exerts a potential anti-inflammatory effect: Data from the ATTIRE trial.

Nonselective B-blockers (NSBBs) are believed to have pleiotropic effects beyond reducing portal pressure. However, studies also report potential harm in patients hospitalized with cirrhosis and ascites. We therefore investigated whether NSBB use at ATTIRE trial entry (Albumin to prevent infection in chronic liver failure, 2016-19) was associated with increased renal or cardiovascular dysfunction, compared the incidence of infection and plasma markers of systemic inflammation, and examined mortality at 28-days, 3 and 6-months. In ATTIRE patients grouped by NSBB use at trial entry, we studied infection at baseline, hospital acquired infection and organ dysfunction during trial treatment period and mortality, with propensity score matching to account for differences in disease severity. There were no differences in renal or cardiovascular dysfunction between patients treated with NSBBs or not, during days 3-15 of hospitalization, despite elevated serum creatinine in NSBB patients at hospitalisation. Use of NSBBs was associated with a significant reduction in infection at hospitalization (p=0.006), lower white cell counts throughout hospital stay (p<0.001) and reduced plasma procalcitonin (p=0.009) and interlukin-8 levels (p=0.04) at baseline, but markers of bacterial translocation and systemic inflammation were the same in treatment groups. There was no reduction in hospital acquired infections in patients taking NSBBs and no beneficial impact on mortality at 28-days, 3 and 6-months. Our real-world data from a completed randomised trial show that use of NSBBs in decompensated cirrhosis patients is safe during hospitalisation. We also show a potential anti-inflammatory role for NSBBs which may be mediated by a downregulation of IL-8 induced leucocytosis, that was associated with reduced infection at baseline but not a survival benefit. Wellcome Trust and Department of Health and Social Care.

Ancestry, ACKR1 and leucopenia in patients with systemic lupus erythematosus

ObjectiveSLE is more prevalent in populations of African (AA) than European ancestry (EA) and leucopenia is common. A homozygous variant in ACKR1 (rs2814778-CC) is associated with lower white cell counts;...

Identifying Recurrence Risk Factors in CT-Confirmed Acute Appendicitis in Adults Managed Non-operatively During the COVID-19 Pandemic.

Background/Objective: Acute appendicitis (AA) is predominantly managed with appendectomy, but can be treated non-operatively, leading to a high risk of recurrence. Non-operative management has been more common since the COVID-19 pandemic affected the feasibility of performing surgery. This case-control study analyzed non-operatively managed patients in order to identify clinical and radiological factors associated with recurrence risk. Methods: Over 12 months, 48 adults with CT-proven AA managed non-operatively were identified, and followed up for at least six further months to assess them for recurrence (readmission to hospital more than 14 days after discharge and after symptom resolution, requiring treatment for appendicitis). Clinical and CT data were collected and a Cox regression survival analysis was performed to produce hazards ratios (HRs).Results: Of the 48 patients, 12 (25%) experienced a recurrence up until the end of the follow-up period, eight of whom were then treated operatively, and four treated non-operatively. On the univariate analysis, greater recurrence risk was observed in patients with diabetes mellitus, higher heart rate (on admission and maximum value during admission), lower white cell count and neutrophils and appendiceal wall thinning on CT. On the multivariate analysis, diabetes mellitus (HR=7.72, p=0.021) and higher heart rate (HR=1.08, p=0.018) were associated with statistically significant greater recurrence risk.Conclusions: Diabetes mellitus and higher heart rate on admission are associated with greater recurrence risk of AA managed non-operatively. No CT findings were associated with statistically significant greater risk. Clinicians should, therefore, consider DM and heart rate when making decisions on appendicitis management, especially during the COVID-19 pandemic but also beyond it.

SP11.4 Imaging recommendations during the Covid pandemic for the investigation of right iliac fossa pain: an unachievable and unnecessary burden on radiology services?

AimsInitial Covid-19 surgical guidance, produced without radiological input, recommended that patients with right iliac fossa (RIF) pain should have imaging before intervention. This study quantified the burden on imaging services from these guidelines.MethodsPatients who presented to our surgical unit with RIF pain from March to October 2020 were identified. Clinical parameters, radiology and final diagnosis were recorded. Minimum follow-up was 12 months to identify re-admissions and morbidity.ResultsThere were 417 patients. There was a drop in admissions in the first months of each new wave of Covid (March/April, September/October) compared with intervening months (36% vs. 64%, P=0.036). 266 patients (64%) had a CT scan increasing from 42% of patients in March to 75% in September (P=0.019). The proportion of patients with normal imaging increased correspondingly with over a third (34%) of CT scans being normal. 93 CT scans (35%) showed appendicitis, which was the suspected diagnosis in all but 7 of these patients.Patients with normal imaging had lower white cell counts (Mean 10.1×109 vs. 14.8×109/L, P<0.001) and CRPs (Mean 21 vs. 99, P<0.001). Patients seen first by a consultant were less likely to require imaging.ConclusionsDuring the first year of Covid-19, two-thirds of patients with RIF pain had a CT scan with a third being normal. Most scans showing appendicitis had clinical parameters consistent with this diagnosis. Current guidelines may lead to unsustainable pressures on radiology services; ensuring consultant assessment prior to imaging requests may reduce the burden on these teams.

MicroRNA-125b Accelerates and Promotes PML-RARa-driven Murine Acute Promyelocytic Leukemia

ObjectiveMost acute promyelocytic leukemia cases are characterized by the PML-RARa fusion oncogene and low white cell counts in peripheral blood. MethodsBased on the frequent overexpression of miR-125-family miRNAs in acute promyelocytic leukemia, we examined the consequence of this phenomenon by using an inducible mouse model overexpressing human miR-125b. ResultsMiR-125b expression significantly accelerates PML-RARa-induced leukemogenesis, with the resultant induced leukemia being partially dependent on continued miR-125b overexpression. Interestingly, miR-125b expression led to low peripheral white cell counts to bone marrow blast percentage ratio, confirming the clinical observation in acute promyelocytic leukemia patients. ConclusionThis study suggests that dysregulated miR-125b expression is actively involved in disease progression and pathophysiology of acute promyelocytic leukemia, indicating that targeting miR-125b may represent a new therapeutic option for acute promyelocytic leukemia.

Predictors of poor haematopoietic stem cell mobilisation in patients with haematological malignancies at a South African centre

BackgroundAutologous stem cell transplant (ASCT) is an established consolidation strategy in the treatment of haematological malignancies, however poor mobilisation (PM) can contribute to patient morbidity and high resource utilisation. Identifying the incidence, risk factors for PM and engraftment outcomes are important goals in our resource limited setting. MethodsWe retrospectively analyzed patients with haematological malignancies that consecutively underwent ASCT at Groote Schuur hospital, Cape Town, South Africa from January 2013 to January 2019. Results146 patients – majority with multiple myeloma (MM)(41,8%), F:M= 1:2, underwent leukapheresis with median age of 32 years (range, 9 – 66 years). PM occurred in 25/146 (17%), mobilisation failure (MF) in 3/146 (2%) and super mobilisation (SMs) in 99/146 (68%), respectively. Risk factors for PM were: diagnosis of acute leukaemia (RR = 25, 95% CI 3.4 – 183, p = 0.002) and Hodgkin lymphoma (RR = 19, 95% CI 2.6 – 142, p = 0.004); low white cell count (WCC) at harvest (WCC < 9 × 109/L (RR=4.3, 95% CI 2.3 – 8.3, p < 0.0001) and two vs one line of prior therapy (RR = 3.1, 95% CI 1.45 – 6.7, p = 0.0037). Median days to neutrophil and platelet engraftment were 14 days (95% CI 14–15 days) and 16 days (95% CI 15–16 days) respectively. ConclusionPM occurred in 17% of a contemporary South African ASCT cohort, albeit with a low MF rate (2%). There was surprisingly high rate (68%) of SMs, possibly reflective of superfluous mobilisation strategy in MM patients. We identified predictive factors for PM that will lead to enhanced cost-effective use of plerixafor.

Predictors of Influenza PCR Positivity in Acute Exacerbations of Chronic Obstructive Pulmonary Disease.

PurposeInfluenza infection is an important cause of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Clinical features predicting influenza PCR positivity are unknown. We aim to identify predictors of influenza PCR positivity in AECOPD.Patients and MethodsA retrospective study of AECOPD cases admitted between 1st January 2016 to 30 June 2017 with combined nasal/throat swabs sent for influenza PCR (Xpert Xpress Flu/RSV) within 24 hours of admission was performed. Clinical parameters and investigations within 24 hours of admission were retrieved from electronic medical records.ResultsInfluenza PCR were sent for 925 AECOPD cases (mean age 75 years, 87.9% male). There were 90 PCR positive cases (68 Influenza A, 22 Influenza B). Influenza PCR positive cases had higher temperatures, higher heart rates, lower white cell and lower eosinophil counts. Age, gender, COPD severity, comorbidities and smoking status were similar in both groups. There were no differences in blood pressure, oxygen status, neutrophil or lymphocyte counts, C reactive protein, procalcitonin or chest X-ray consolidation between groups. Higher temperature, higher heart rate, white cell count in the lowest quartile (Q1 < 8.1 x109/L) and non-eosinophilic exacerbations predicted influenza PCR positivity on univariate logistic regression and these factors remained significant after multivariate adjustment (temperature adjusted odds ratio [adj OR] 1.324 [1.009–1.737], p = 0.043; heart rate adj OR 1.017 [1.004–1.030], p = 0.011; white cell count Q1 adj OR 3.330 [1.690–6.562], p = 0.001; eosinophilic exacerbations adj OR 0.390 [0.202–0.756], p = 0.005).ConclusionHigher temperature, higher heart rate, low white cell count (especially when < 8.1 x109/L) and non-eosinophilic exacerbations are independent predictors of influenza PCR positivity in AECOPD cases.

Clinical Characteristics and Inflammatory Immune Responses in COVID-19 Patients With Hypertension: A Retrospective Study.

Coronavirus disease (COVID-19) patients with cardiovascular and metabolic disorders have been found to have a high risk of developing severe conditions with high mortality, further affecting the prognosis of COVID-19. However, the effect of hypertension and angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blocker (ARB) agents on the clinical characteristics and inflammatory immune responses in COVID-19 patients is still undefined. In this study, 90 COVID-19 patients were divided into hypertension and nonhypertension groups. The hypertension group was divided into well-controlled and poorly controlled subgroups based on blood pressure levels; moreover, hypertensive patients were also divided into ACEI/ARB and non-ACEI/ARB subgroups according to the administration of ACEI/ARB antihypertensive agents. The clinical characteristics of and inflammatory immune biomarker levels in the different groups of COVID-19 patients were compared, and the association between the combined effect of hypertension with ACEI/ARB antihypertensive agents and the severity of COVID-19 was examined. The results showed that the levels of aminotransferase (AST) and hs-cTnI were higher in the hypertension group compared with the nonhypertension group. The long-term use of ACEI/ARB agents in patients had statistically significantly lower AST, low-density lipoprotein cholesterol (LDL-C), and oxygen uptake and lower white cell count, neutrophil count, and levels of CD4, CD8, CRP, and PCT but without statistical significance. In addition, compared with COVID-19 patients without hypertension, hypertensive patients without the use of ACEI/ARB had a higher risk of developing severity of COVID-19 (for poorly controlled patients: OR = 3.97, 95% CI = 1.03–15.30; for well-controlled patients: OR = 6.48, 95% CI = 1.77–23.81). Hypertension could cause organ damage in COVID-19 patients, but the long-term use of ACEI/ARB agents may be beneficial to alleviate this injury.

A COMPREHENSIVE SURVEY OF COVID–19 DETECTION USING CLOSED MOLECULAR TECHNIQUES IN THE URBAN CITY OF GUJARAT

At the end of 2019 a novel virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing severe acute respiratory syndrome amplied globally from Wuhan, China. In March 2020 the World Health Organization (WHO) declared the SARS-Cov-2 virus a global pandemic. The disease is spread through inhalation or contact with infected droplets and the incubation period ranges from 2 to 14 days. The symptoms are usually fever, cough, sore throat, breathlessness, fatigue, weakness others. The disease is moderate in most people. It may continue to pneumonia, acute respiratory distress syndrome (ARDS), and multi-organ dysfunction. Many people are asymptomatic. Diagnosis is by the presentation of the virus in respiratory secretions by special molecular tests. Common laboratory ndings include normal and or low white cell counts with elevated C-reactive protein (CRP). The computerized tomographic chest scan is usually abnormal even in those with asymptomatic or mild disease. Prevention leads to home isolation of suspected cases and those with mild illnesses and strict infection control measures at hospitals that include contact and droplet precautions. Due to the current review, we summarized and equally analyze the emergence and pathogenicity of COVID 19 infection and previous human coronavirus severe acute respiratory coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERSCoV). In Particular, focus on public health impact, pathophysiology and clinical manifestation, diagnosis, case management.

Is Sepsis a Risk Factor for Bleeding in Adults with Hematologic Malignancies?

BackgroundThe TOPPS trial (Trial of Prophylactic vs. No-Prophylactic Platelet Transfusions in Patients with Haematological Malignancies) provides a resource to explore to what degree different patient factors or clinical characteristics are important prognostic factors for bleeding. A previous analysis of the TOPPS data has looked at risk factors for bleeding on data that was collected at all study centres, this included: female sex; hematologic diagnosis; treatment for their hematologic diagnosis; and TOPPS treatment arm (prophylaxis/no-prophylaxis).This study aims to look at additional factors that were not assessed in previous analyses of TOPPS data.MethodsWe collected additional data on potential risk factors for bleeding at two study centres (Oxford and Glasgow) on 219 patients with a total of 3454 observations, as a sub-study of the TOPPS trial (ISRCTN08758735). Bleeding information was reported for over 95% of study days. It was necessary to remove all study day 1 observations (as previous day lab values were not know), therefore 3084 observations were included in the recurrent event analysis.We collected additional data on: Hb; WCC; albumin; bilirubin; creatinine; use of antibiotics; use of antifungals; admission to ITU; use of oxygen; CRP; temperature. This additional data was only available while patients were inpatients, however most bleeds that occurred during the TOPPS trial occurred while the patient was in hospital (94%). Only the first day of consecutive bruising or petechiae was counted as a bleed, unless bleeding on the subsequent day was worse.Bleeding assessments were performed daily and assessed bleeding over the preceding 24 hours. The blood results performed on the day prior to the bleeding assessment were in the same 24 hour period as any bleeding occurred. Analyses were performed that took missing data into account or only included the full data set. Variables considered in the model were: female sex, hematologic diagnosis; treatment for their hematologic diagnosis; TOPPS treatment arm; age; platelet count; relapsed disease; previous HSCT; Hb; WCC; albumin; bilirubin; creatinine; use of antibiotics; use of antifungals; admission to ITU; use of oxygen; CRP; temperature.ResultsBaseline characteristics were similar to all patients within the TOPPS study. The only differences noted between the Oxford and Glasgow groups and the overall study were: higher proportion of patients receiving an allogeneic HSCT; and a higher proportion of patients with a co-existing disorder or organ failure (13% vs. 7%). The median number of days with a WHO grade 2-4 bleed was 0 days (IQR 0 to 1).In the univariate analysis: TOPPS treatment arm (P = 0.02); female sex (P = 0.002); previous HSCT (P = 0.03); previous day C-reactive protein (CRP) (P < 0.0001); previous day Hb (p < 0.0001); previous day WCC (P < 0.0001); previous day creatinine (P < 0.0001); treatment with therapeutic antibiotics (P < 0.0001); ITU/HDU admission (P = 0.04); oxygen treatment (P < 0.0001); high temperature (P = 0.02); and previous day's platelet count were associated with bleeding (P < 0.0001).In the multivariate recurrent event analyses we investigated factors associated with the hazard of a grade 2 to 4 bleed on any one day. Female sex (hazard ratio (HR) 1.7 ; 95% CI 1.3 to 2.2; P < 0.0001); previous day platelet count (0 to 20 x 109/L versus > 50 x 109/L: HR 3.3; 95% CI 1.4 to 7.9; P = 0.0002), previous day CRP (100 to 150 versus 0 to 9 mg/L: HR 1.7; 95% CI 1.0 to 3.0; P = 0.03); previous day creatinine (121 to 180 versus 0 to 90 µmol/L: HR 1.9; 95% CI 1.3 to 2.8: P = 0.02); and previous day WCC (0 to 0.4 x 109/L versus > 3.4 x 109/L: HR 2.6; 95% CI 1.4 to 5.0; P = 0.005) were all found to be significantly associated with bleeding in both analyses. TOPPS treatment arm was found to be significant in the full data set analysis (no-prophylaxis versus prophylaxis: HR 1.3; 95% CI 1.0 to 1.7; P = 0.04) but not in the analysis that included missing data.DiscussionThis new analysis of the TOPPS data set identified additional independent risk factors for bleeding that have not been previously identified, these were CRP and low white cell count. It also confirmed risk factors identified in previous analyses on the TOPPS data as well as other clinical trial data sets. CRP was the only significant sepsis-related risk factor. The next step is to use data from this and other analyses to develop a simple model that can stratify patients into different bleeding risk categories.FundingNHSBT DisclosuresNo relevant conflicts of interest to declare.

Clinical prediction tools to identify patients at highest risk of myeloma in primary care: a retrospective open cohort study.

BackgroundPatients with myeloma experience substantial delays in their diagnosis, which can adversely affect their prognosis.AimTo generate a clinical prediction rule to identify primary care patients who are at highest risk of myeloma.Design and settingRetrospective open cohort study using electronic health records data from the UK’s Clinical Practice Research Datalink (CPRD) between 1 January 2000 and 1 January 2014.MethodPatients from the CPRD were included in the study if they were aged ≥40 years, had two full blood counts within a year, and had no previous diagnosis of myeloma. Cases of myeloma were identified in the following 2 years. Derivation and external validation datasets were created based on geographical region. Prediction equations were estimated using Cox proportional hazards models including patient characteristics, symptoms, and blood test results. Calibration, discrimination, and clinical utility were evaluated in the validation set.ResultsOf 1 281 926 eligible patients, 737 (0.06%) were diagnosed with myeloma within 2 years. Independent predictors of myeloma included: older age; male sex; back, chest and rib pain; nosebleeds; low haemoglobin, platelets, and white cell count; and raised mean corpuscular volume, calcium, and erythrocyte sedimentation rate. A model including symptoms and full blood count had an area under the curve of 0.84 (95% CI = 0.81 to 0.87) and sensitivity of 62% (95% CI = 55% to 68%) at the highest risk decile. The corresponding statistics for a second model, which also included calcium and inflammatory markers, were an area under the curve of 0.87 (95% CI = 0.84 to 0.90) and sensitivity of 72% (95% CI = 66% to 78%).ConclusionThe implementation of these prediction rules would highlight the possibility of myeloma in patients where GPs do not suspect myeloma. Future research should focus on the prospective evaluation of further external validity and the impact on clinical practice.

Fluid requirement in adult dengue haemorrhagic fever patients during the critical phase of the illness: an observational study

BackgroundDengue fever prevalence is rising globally and it causes significant morbidity and mortality. Fluid extravasation during the critical phase of dengue haemorrhagic fever (DHF) leads to shock, multi-organ failure and death if not resuscitated appropriately with fluids. The mainstay of management is judicious fluid replacement using a guideline based, calculated fluid quota of maintenance (M) fluid plus 5% deficit (M + 5% deficit) to prevent organ hypoperfusion.MethodsWe conducted an observational follow-up study in Sri Lanka from January–July 2017 to identify the fluid requirements of DHF patients and to identify whether features of fluid overload are present in patients who exceeded the fluid quota. Patients who developed DHF following admission to the place of study, were recruited and the amount of fluid received during the critical phase was documented.ResultsA total of 115 DHF patients with a mean age of 30.3 (SD 12.2) years were recruited to the study. There were 65 (56.5%) males and the mean fluid requirement was 5279.7 ml (SD 735) over the 48 h. Majority of the study participants (n = 80, 69.6%) received fluid in excess of the recommended maintenance + 5% deficit and this group had higher body mass index (22.75 vs 20.76, p0.03) and a lower white cell count at the onset of the critical phase (3.22 × 103 vs 4.78 × 103, p < 0.001). The highest fluid requirement was seen within the first 12 and 24 h of the critical phase in patients requiring fluid M + 5%–7.5% deficit and ≥ M + 7.5% deficit respectively. Patients exceeding M + 5% deficit had narrow pulse pressure and hypotension compared to the rest. DHF grades III and IV were seen exclusively in patients exceeding the fluid quota indicating higher amount of fluid was given for resuscitation. Fluid overload was detected in 14 (12.1%) patients and diuretic therapy was required in 6 (5.2%) patients.ConclusionsThe majority of patients received fluid in excess of the recommended quota and this group represents patients with narrow pulse pressure and hypotension. Although, fluid overload was infrequent in the study population, clinicians should be cautious when administering fluid in excess of M + 7.5% deficit.

Acute appendicitis in people living with HIV: What does the emergency surgeon needs to know?

Acute appendicitis is among the commonest surgical emergencies seen in an acute setting. Individuals living with the Human Immunodeficiency Virus (HIV) and/or the Acquired Immunodeficiency Syndrome (AIDS) have an increased risk of encountering complications with acute appendicitis. We conducted a literature search using the words appendicitis and HIV in google scholar, Medline, Scopus and PubMed. The search also extended to cover HIV presented with acute appendicitis, their outcome during and following the management of acute appendicitis. Several studies showed that HIV is associated with a higher rate of acute appendicitis than the general population. HIV can directly affect the appendix, through opportunistic infections, immune reconstitution inflammatory syndrome associated with start of antiretroviral medication. High index of suspicion is needed to exclude conditions that mimic acute appendicitis (abdominal tuberculosis, pyelonephritis, cytomegalovirus, cryptosporidium, pneumococcus, Amoebic appendicitis and pill impaction). The clinical presentation may not be typical of acute appendicitis and can be associated with low white cell count and variable fever. The Alvarado score for predicting acute appendicitis can be used and more research is needed to establish cut-off point value. Computed tomography scan and ultrasound are widely used in clinical diagnosis. Importantly, acute appendicitis with HIV/AIDS can be associated with high rate of post-surgical complications like infections, delay of healing, perforation, peritonitis, intra-abdominal abscess and longer hospital stay. HIV/AIDS with acute appendicitis is complex condition. Therefore, we conclude that patients with known HIV and acute appendicitis should also be managed in close liaison with HIV physicians during, before and after surgical treatment.

Evolving Changes in the Full Blood Count in Tuberculosis

Abstract Background: Changes in the full blood count of patients with tuberculosis have been studied previously, but the effect of co-infection with human immunodeficiency virus (HIV) remains to be explored. Objective: To evaluate the changes in full blood count in patients with tuberculosis in an evolving HIV era. Methods: Prospective study of consecutively recruited patients (N = 125) with microbiologically or histologically proven tuberculosis admitted at Chris Hani Baragwanath Academic Hospital between October 2017 and July 2018. Results: Anaemia was found in 60.7% of patients with pulmonary tuberculosis (PTB) and in 61.1% of extra-pulmonary tuberculosis (ETB) patients. ETB patients had lower white cell counts (WCCs) and lower neutrophil counts than PTB patients, (5.59 (3.6–8.1) vs 7.96 (5.27–10.34), p = 0.002) and (4.2 (2.1–7.0) vs 5.5 (3.3–8.4), p = 0.079), respectively. Compared to the HIV-seronegative patients, HIV co-infected PTB patients had lower WCC, lymphocyte counts and neutrophil counts, (6.9 (4.8–9.7) vs 9.4 (8.6–11.4), p = 0.0037), (0.7 (0.46–1.31) vs 1.51 (1.13–2.05), p = 0.0051), and (4.7 (2.8–7.7) vs 8.5 (5.9–10.1), p = 0.0106), respectively. Patients co-infected with HIV on combination antiretroviral therapy and tuberculosis had higher levels of WCC, (7.9 (4.6–10.9) vs 5.8 (4.3–8.3), p = 0.0465). Conclusion: Anaemia is the most common manifestation of tuberculosis. This study highlighted the reactive nature of PTB haematological abnormalities compared to ETB with higher WCCs in both HIV-seropositive and HIV-seronegative patients. Co-infection with HIV was associated with blunting of some of the previously described haematological manifestations among patients with PTB.

Effect of ultra-diluted nux vomica and cyclophosphamide solutions on the genotoxicity of allopathic cyclophosphamid

Homeopathic medicines comprise the use of pharmacotechnical processes that promote successive dilutions, followed by grinding or agitation of compounds. The purpose of this study was to assess the genotoxic potential of ultra-diluted cyclophosphamide (CF) and nux vomica associated with or without allopathic CF in Swiss Webster mice, using the micronucleus test. The compounds were prepared according to the Brazilian homeopathic pharmacopoeia. Swiss Webster mice were randomly divided into eight groups (n=6) according to the compounds to be tested and received by gavage (vehicle or CF) or by oral mucosa contact (ultra-diluted CF and nux vomica, and dynamized solutions) once a day for 7 days. After this, one of the groups treated with the dynamized compound was challenged by the administration of the allopathic CF. The dynamized ultra-diluted nux vomica and CF compounds showed lower white cell counts in mice. However, no compound was able to mitigate the genotoxic effects of CF in micronucleus assay. The dynamized compounds did not cause damage to the spleen and thymus, and when used intraperitoneally, they were able to mitigate the effect of CF on thymic cortical reduction in mice. Further studies with nux vomica and dynamized CF should be performed to better delineate their possible therapeutic potential in reducing adverse effects on chemotherapy.