Can vacuum-formed retainers maintain arch dimensions and alignment compared to Hawley and fixed bonded retainers after treatment with fixed appliances? A systematic review and meta-analysis.

BACKGROUND: Different types of retention appliances have been proposed over the years, but their effectiveness in maintaining arch dimensions and alignment after orthodontic treatment is still unclear. AIM: To assess the efficacy of vacuum-formed retainers (VFRs) in preserving arch widths, arch length, and anterior alignment in maxillary and mandibular arches, compared to removable Hawley retainers (HRs) or fixed bonded retainers (FBRs). Search methods: unrestricted literature search of five major databases up to March 2024. SELECTION CRITERIA: randomized/non-randomized clinical studies comparing VFRs to removable HRs or FBRs. DATA COLLECTION AND ANALYSIS: after duplicate study selection, data extraction, and risk of bias assessment, random effects meta-analyses of standardized mean differences and their 95% confidence intervals were performed, followed by meta-regressions, sensitivity analyses, and assessment of the quality of evidence with GRADE. RESULTS: Twenty-two prospective studies (4 non-randomized and 18 randomized controlled trials) involving 1797 patients (mean age 17.01 years, 38.3% males) were included. No significant differences were found in the intercanine width, intermolar width, and arch length between VFRs and HRs, in both arches (P > 0.05). However, VFRs were statistically more effective than HRs in terms of Little's irregularity scores (LII) in the maxilla (eight studies; SMD = -0.42; 95% CI: -1.03 to -0.09; P = 0.02; I2 = 73.4%) but not in the mandible (P = 0.12). No significant differences were reported for all considered outcomes between VFRs and FBRs in in both arches (P > 0.05), except for lower LII, where VFRs were significantly less efficient (eight studies; SMD = 1.49; 95% CI = 0.26-2.7; P = 0.02; I2 = 93%). Follow-up times, risk of bias, and wire type (of FBRs) did not show statistically significant effects on outcome variables. Sensitivity analyses showed robustness of the findings for including non-randomized and postretention studies. The certainty in these estimates was from moderate to low due to the risk of bias and inconsistency. CONCLUSIONS: Low to moderate quality evidence indicates that VFRs are as effective as HRs in maintaining arch widths, length, and alignment. Low-quality evidence found similar efficacy between VFRs and FBRs, with FBRs being statistically more effective at maintaining lower arch alignment, but the difference was not clinically significant. REGISTRATION: PROSPERO registration (CRD42024518433).

Influence of elastomeric and steel ligatures on periodontal health during fixed appliance orthodontic treatment: a systematic review and meta-analysis.

INTRODUCTION: Metallic and elastomeric ligatures are widely used in orthodontics to secure the archwire within the bracket slots, but elastomeric ligatures have traditionally been associated with increased microbial colonization, which could adversely affect periodontal health. AIM: This systematic review compares the periodontal effects of elastomeric and steel ligatures used for orthodontic fixed appliances. METHODS: Unrestricted literature search of 7 databases (MEDLINE, Scopus, Web of Science, Embase, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and Virtual Health Library) up to July 2023 were performed for randomized / non-randomized clinical studies on humans comparing the two ligation methods during fixed-appliance therapy. After duplicate study selection, data extraction, and risk-of-bias assessment with the Risk of Bias (RoB) 2 or the Risk Of Bias In Non-randomized Studies - of Interventions (ROBINS-I) tool, random-effects meta-analyses of Mean Differences (MD) or Standardized Mean Differences (SMD) and their 95% confidence intervals (CIs) were carried out, followed by assessment of certainty of existing evidence with the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach. RESULTS: A total of 11 studies (3 randomized / 8 non-randomized) with 354 patients (mean age 14.7 years and 42% male) were included. No statistically significant differences were seen for plaque index (5 studies; SMD = 0.48; 95% CI = -0.03 to 1.00; P = 0.07), gingival index (2 studies; MD = 0.01; 95% CI = -0.14 to 0.16; P = 0.89), probing pocket depth (2 studies; MD = 0; 95% CI = -0.17 to 0.16; P = 0.97), or Streptococcus mutans counts (4 studies; SMD = 0.40; 95% CI=-0.41 to 1.20; P = 0.21). Elastomeric ligatures were associated with moderately increased total bacterial load (3 studies; SMD = 0.43; 95% CI = 0.10 to 0.76; P = 0.03). Confidence in these estimates was low in all instances due to the inclusion of non-randomized studies with high risk of bias. CONCLUSIONS: Existing low quality evidence indicates that ligature method does not seem to influence the periodontal health during fixed treatment, even if elastomeric ligatures are associated with a moderate increase of bacterial load. REGISTRATION: PROSPERO (CRD42023444383).

Inter-observer and intra-observer agreement of cervical vertebral maturation staging: A systematic review and meta-analysis.

INTRODUCTION: The accurate assessment of active growth is pivotal for the correction of skeletal malocclusion in growing patients. Cervical vertebral maturation (CVM) staging is easy and devoid of unnecessary radiation, but its inter- and intra-observer agreement is still debatable. OBJECTIVE: This study aims to assess inter-observer (reliability) and intra-observer agreement (reproducibility) for CVM staging. METHODS: A comprehensive literature search across five databases up to October 2023 was conducted. Inclusion criteria comprised observational studies that specifically reported intra-rater, inter-rater, or both agreements as their primary objectives for cervical vertebral maturation (CVM) staging. Studies with a sample size exceeding 15 participants were considered for inclusion. After duplicate study selection, data extraction, and risk-of-bias assessment, random-effects meta-analyses of kappa (k)/correlation coefficient (r) and their 95% confidence intervals (CIs) were performed, followed by meta-regressions, sensitivity analyses, and subgroup analyses. RESULTS: Seventeen observational studies (comprising 1437 lateral cephalograms and 110 assessors) were included. The reliability (8 studies; k=0.62 [95% CI: 0.44, 0.78]) and reproducibility (9 studies; k=0.708 [95% CI: 0.59, 0.82]) were substantial. The inter-observer correlation was almost perfect (in 9 studies; r=0.86 [95% CI: 0.82, 0.89]) while intra-observer correlation was substantial (in 2 studies; r=0.75 [95% CI: 0.62, 0.84]). Tracing of lateral cephalograms significantly increased inter-observer reliability (ß=0.29 [0.57, 0.0031]) but cropping and time of assessment (initial vs. follow-up) had no significant impact. The reliability (P<0.001) and reproducibility (P=0.049) of high-quality studies were superior to those observed in low-quality studies. CONCLUSION: Assessment of the CVM staging is accurate and reproducible to a satisfactory level. The accuracy and reproducibility of CVM are higher in studies utilizing traced cephalograms and those with a low-risk of bias. REGISTRATION: PROSPERO registration (CRD42023468521). Data is openly available at https://doi.org/10.5281/zenodo.10599129.

Synchronous Carotid Body and Glomus Jugulare Tumors : A Case Report and Review of Literature.

Paragangliomas are rare neuroendocrine tumors that are usually benign in nature. They may be either familial or sporadic in their occurrence. Numerous neuroendocrine tumors are collectively included under the umbrella of paragangliomas. Among them, carotid body tumors and glomus jugulare tumors are extremely rare. Thus, we present a rare case of 29-year-old male who was admitted with hearing difficulties and tinnitus in the left ear, with swelling on the left side of the neck. Based on clinical and radiological findings, a diagnosis of left-sided glomus jugulare with carotid body tumor was made. The patient underwent a twostage surgery with an interval of approximately 2 months. Histopathology revealed a paraganglioma. Herein, we present the clinical features, imaging findings, management, and a brief review of literature on the classification, evaluation, and management of carotid body and glomus jugulare tumors. Paraganglioma is a slow-growing tumor. The synchronous occurrence of carotid body and glomus jugulare tumors is infrequent. Microsurgical resection remains the primary treatment modality. Therefore, our patient underwent two-stage surgery. The rarity of occurrence and the proximity and adherence to vital neurovascular structures have resulted in the treatment of paragangliomas remaining a challenge.

Oral health behind the bars: oral health seeking behavior among jail prisoners at central jail of Peshawar, Pakistan: a cross-sectional study.

BACKGROUND: The oral health care-seeking behavior among prison inmates is an overlooked area, often leading to deteriorating general health due to the prisoners' limited awareness of oral hygiene practices. It is crucial to address this issue and understand the factors associated with oral healthcare-seeking behavior in prisons. OBJECTIVE: To assess the oral healthcare-seeking behavior of prison inmates at Central Prisoner Jail, Peshawar Pakistan and to look the factors associated with their dental care utilization. MATERIAL AND METHODS: This cross-sectional study was conducted at Central Prisoner Jail, Peshawar Khyber Pakhtunkhwa, Pakistan from November 2021 to April 2022. A consecutive sampling technique was used to collect data from both convicted and under-trial prisoners by using a pre-tested WHO Basic Oral Health Survey 2013 tool. Our outcome variable was "Visit to a dentist in the last 12 months (Never/Once or more than one visit). Chi-square test was used to determine univariate association with other explanatory variables while multivariable logistic regression was performed to adjust for potential confounders. RESULT: A total of 225 participants were recruited to the study with a mean (SD) age of 32.9(11.4). More than two-thirds of 200(88.9%) of the participants were males. One-third of the sample never visited the dentist75(33.3). Participants who completed college/university education and never visited the dentist in the last 12 months constituted a smaller proportion (17.6%) compared to those who visited the dentist once or more than once n = 28(82.4%, p-value = 0.003). Individuals who were using toothbrushes were most frequently visiting the dentist n = 130(72.6%=p value = 0.001) as compared to never visitors. Multivariate logistic regression analysis revealed that Participants who experienced teeth pain or discomfort had 0.42 times lower odds of visiting the dentist compared to those who did not experience any pain or discomfort [AOR 0.42 (95% CI 0.17-0.80), p = 0.04]. Similarly, Participants who do not use any denture have 4.06 times higher odds[AOR 4.06(95% CI 1.76-9.36), p = 0.001] of visiting the dentist compared to those who use a denture. CONCLUSION: Our result demonstrates that those prisoners who were experiencing tooth pain or discomfort and not using dentures were the strong predictors with lower dental visit frequency to seek oral health care.

Extended Endonasal Endoscopic (EEE) Surgery with Almost No Use of Adjuvant Radiotherapy for Juvenile Nasopharyngeal Angiofibroma (JNA).

Background and Objectives: Juvenile nasopharyngeal angiofibroma (JNA) is an angiomatous hamartoma of the nasal cavity. It is a benign but locally aggressive vascular tumor of the nasopharynx affecting adolescent males. Many surgical procedures are in practice, but the extended endonasal endoscopic (EEE) approach for JNAs is a suitable and effective technique. Materials and Methods: Fifteen adolescent patients having JNA who underwent extended endonasal endoscopic (EEE) surgery from January 2010 to January 2022 were studied retrospectively. Patients having residual and recurrent JNAs and those who underwent surgery other than EEE were excluded. Results: The average age of the patients was 18.3 years of age. A total of six patients (40%) each had stage V and IV while three patients (20%) had stage III JNAs. Gross total removal was achieved in eight (53.3%) patients and seven (43.7%) had partial removal. There was no per or postoperative mortality. All the patients had at least 3 years of postoperative follow-up and during follow-ups, seven patients were found to have residual tumors, and two had recurrences. Discussion: During the last decades, the endoscopic approach for the resection of JNAs has gained increasing popularity due to its obvious advantages over transfacial approaches. The magnified and angled field of view "behind the corner" helping in a more complete inspection for the resection and shorter hospitalization time makes it a better choice than the other approaches. Conclusions: Endoscopy is an excellent approach for primary JNA. It allows well visualization and precise removal of the angiofibroma. An endoscopic multiangle, multicorridor skull base approach including Denker's anteromedial maxillotomy is suitable and preferable for the resection of extensive JNAs.

Effects of chlorhexidine use on periodontal health during fixed appliance orthodontic treatment: a systematic review and meta-analysis.

BACKGROUND: Proper oral hygiene and absence of periodontal inflammation is pre-requisite for orthodontic treatment. Chlorhexidine (CHX) is an established oral antiseptic used in the treatment of periodontal disease, but its role in orthodontic therapy is unclear. OBJECTIVES: To assess the efficacy of adjunct use of CHX-containing products in maintaining gingival health among orthodontic patients with fixed appliances. SEARCH METHODS: Five databases were searched without limitations up to August 2021. SELECTION CRITERIA: Randomized clinical trials (RCTs) assessing Gingival Index (GI) (primary outcome), Plaque Index (PI), Bleeding Index (BI), or Pocket Probing Depth (PPD). DATA COLLECTION AND ANALYSIS: Study selection, data extraction, and risk of bias assessment were done independently in duplicate. Random-effects meta-analyses of mean differences (MDs) or standardized mean differences (SMDs) with their 95% confidence intervals (CIs) were conducted, followed by sensitivity and Grades of Recommendations, Assessment, Development and Evaluation analysis. RESULTS: Twenty RCTs (1001 patients) were included assessing CHX-containing mouthwashes (n = 11), toothpastes (n = 2), gels (n = 3), or varnishes (n = 4) compared to placebo/control (n = 19) or sodium fluoride-products (n = 4). In the short-term, CHX-containing mouthwash was associated with lower GI (n = 9; MD = -0.68; 95% CI = -0.97 to -0.38; P < 0.001; high quality), lower PI (n = 9; MD = -0.65; 95% CI = -0.86 to -0.43; P < 0.001; high quality), lower BI (n = 2; SMD = -1.61; 95% CI = -2.99 to -0.22; P = 0.02; low quality), and lower PPD (n = 2; MD = -0.60 mm; 95% CI = -1.06 to -0.14 mm; P = 0.01; low quality). No considerable benefits were found from the use of CHX-gel or CHX-varnish in terms of GI, PI, or PPD (P > 0.05/low quality in all instances). Use of a CHX-containing toothpaste was more effective in lowering PI (Heintze-index) than adjunct use of fluoride-containing mouthwash (n = 2; MD = -5.24; 95% CI = -10.46 to -0.02; P = 0.04), but not GI (P = 0.68) or BI (P = 0.27), while sensitivity analyses indicated robustness. CONCLUSIONS: Adjunct use of CHX mouthwash during fixed-appliance treatment is associated with improved gingival inflammation, plaque control, and pocket depths, but caution is warranted and recommendations about CHX use during orthodontic treatment of children/adults should consider the heterogeneous patient response, cost-effectiveness, and potential adverse effects. REGISTRATION: PROSPERO registration (CRD42021228759).

Skull Base Approaches for Tuberculum Sellae Meningiomas: Institutional Experience in a Series of 34 Patients.

(1) Background: The aim of the present study was to evaluate our institutional outcome in tuberculum sellae meningioma (TSM) patients treated microsurgically using multiple skull base approaches, including a transcranial approach and an extended endonasal transsphenoidal approach. (2) Materials and Methods: This is a retrospective study that includes 34 patients with TSM. The study aimed to observe the efficacy of the different common approaches used by a single neurosurgeon. All the patients were evaluated preoperatively and during follow-up with campimetry, head CT scan, and post-contrast MRI. (3) Results: After a transcranial approach, visual acuity improved in 86.20%, was stable in 10.34%, and deteriorated in 3.45%. Through transsphenoidal surgery, vision improved in 80%, was static in 20%, and deteriorated in 0%. Transcranial approaches included pterional, mini-bifrontal basal, and supraciliary keyhole microscopic craniotomies. Gross total removal was performed in 58.82%, near total in 10.34%, and partial removal in 3.45%. The transcranial/supraciliary keyhole endoscopic-assisted approach showed a gross total removal rate of 80%, and near total in 20%. The transsphenoidal approach showed a gross total removal rate of 60%, near total in 20%, and partial removal in 20%. (4) Conclusion: Endoscopic-assisted keyhole supraciliary mini craniotomy for resection of tuberculum sellae meningioma offers low morbidity and good visual outcome. The endonasal route is preferred for the removal of TSM when they are small and midline placed. The major limitation of this approach is a narrow surgical corridor and the restriction on midline-placed lesions. Gross total removal was better achieved with mini-bifrontal basal and pterional craniotomies.

Nutrition and Food Security in Bangladesh: Achievements, Challenges, and Impact of the COVID-19 Pandemic.

BACKGROUND: Bangladesh has experienced remarkable transformation in demographic, health, and nutritional status of the population. The changes have exposed the population to a number of challenges, the detrimental effect of which on health and nutrition is likely to be increased by the coronavirus disease 2019 (COVID-19) pandemic. We provide an overview of health and nutritional challenges in Bangladesh in relation to demographic transition and the COVID-19 pandemic. METHODS: We identified and reviewed recent reports, published articles, and pertinent gray literature on nutrition and food security in Bangladesh to provide historical and contextual information. RESULTS: The review identifies the progress as well as existing burden regarding nutrition and food security in Bangladesh and highlights the challenges in the coming days in regard to population growth and the COVID-19 pandemic. The country is on track to reduce all forms of childhood undernutrition, while the proportion of nutrition-related noncommunicable diseases is rising owing to changes in dietary intake, low physical activity, and sedentary lifestyle. CONCLUSIONS: Despite remarkable progress, health and nutritional status of the population in Bangladesh faces challenges, particularly in relation to demographic transition and compounded by the COVID-19 pandemic, which require concerted attention from policymakers as well as stakeholders.

Magnetic Resonance Spectroscopy for Prediction of Grades of Diffusely Infiltrating Intracranial Astrocytomas.

Objective Gliomas, the most frequent primary brain tumors, have various grades, among which grade II, III, and IV are diffusely infiltrating astrocytomas. As therapeutic approaches and outcome differ considerably, depending on the grade of these tumors, prediction is important regarding outcome. Magnetic resonance spectroscopy (MRS) can be of help in understanding of the biochemical changes of pathological state to study, monitor, predict grading and outcome of gliomas. Materials and Methods All the 30 patients in the study with intracranial diffusely infiltrating astrocytoma had MRS study using 1.5 Tesla MR scanner. The study population was divided into three groups on the basis of the grades of the tumor according to histopathology. Mean height of choline (Ch), N-acetyl aspartate (NAA), creatine (Cr) peak, and choline/creatine (Ch/Cr) ratio was documented. Mean value of each variable among three grades was analyzed and compared with analysis of variance (ANOVA) test (F-test). Results There was positive relationship regarding Ch/Cr ratio among astrocytomas grade II to IV and the result was significant ( p = 0.047). A positive relationship of Ch peak was also observed for grade II to IV astrocytoma, though the result was not significant ( p = 0.578). The result was nonsignificant for NAA ( p = 0.696) and Cr ( p = 0.740) peak also. Conclusion We recommend Ch/Cr ratio to be considered as a dependable MRS data to comment on low- or high-grade astrocytomas. MRS can be done as a routine investigation in the developing countries for astrocytomas where other facilities are less accessible for reliable prediction and counseling.

Huge Ventral Cervicomedullary Neurenteric Cyst: A Rare Entity with Good Surgical Outcome and Appraisal.

Neurenteric cysts are rare congenital lesions of benign nature that can be encountered at any level of the neuraxis, starting from the cranium down to coccyx. Rewarding outcome can be achieved with early diagnosis and complete removal of these benign lesions. Here, we report a case of a huge neurenteric cyst in an 11-year-old boy at the ventral craniocervical junction, a rarely reported entity with literature review. In this article, we focus on the clinical presentation, pathogenesis, radiological findings, surgery, and surgical outcome of this benign lesion, as we succeeded to have gratifying result following surgery in our instance.

Associations Between Restrictive Fluid Management and Renal Function and Tissue Perfusion in Adults With Severe Falciparum Malaria: A Prospective Observational Study.

BACKGROUND: Liberal fluid resuscitation has proved harmful in adults with severe malaria, but the level of restriction has not been defined. METHODS: In a prospective observational study in adults with severe falciparum malaria, restrictive fluid management was provided at the discretion of the treating physician. The relationships between the volume of fluid and changes in renal function or tissue perfusion were evaluated. RESULTS: A total of 154 patients were studied, 41 (26.6%) of whom died. Median total fluid intake during the first 6 and 24 hours from enrollment was 3.3 (interquartile range [IQR], 1.8-5.1) mL/kg per hour and 2.2 (IQR, 1.6-3.2) mL/kg per hour, respectively. Total fluid intake at 6 hours was not correlated with changes in plasma creatinine at 24 hours (n = 116; rs = 0.16; P = .089) or lactate at 6 hours (n = 94; rs = -0.05; P = .660). Development of hypotensive shock or pulmonary edema within 24 hours after enrollment were not related to the volume of fluid administration. CONCLUSIONS: Restrictive fluid management did not worsen kidney function and tissue perfusion in adult patients with severe falciparum malaria. We suggest crystalloid administration of 2-3 mL/kg per hour during the first 24 hours without bolus therapy, unless the patient is hypotensive.

Acetaminophen as a Renoprotective Adjunctive Treatment in Patients With Severe and Moderately Severe Falciparum Malaria: A Randomized, Controlled, Open-Label Trial.

Background: Acute kidney injury independently predicts mortality in falciparum malaria. It is unknown whether acetaminophen's capacity to inhibit plasma hemoglobin-mediated oxidation is renoprotective in severe malaria. Methods: This phase 2, open-label, randomized controlled trial conducted at two hospitals in Bangladesh assessed effects on renal function, safety, pharmacokinetic (PK) properties and pharmacodynamic (PD) effects of acetaminophen. Febrile patients (>12 years) with severe falciparum malaria were randomly assigned to receive acetaminophen (1 g 6-hourly for 72 hours) or no acetaminophen, in addition to intravenous artesunate. Primary outcome was the proportional change in creatinine after 72 hours stratified by median plasma hemoglobin. Results: Between 2012 and 2014, 62 patients were randomly assigned to receive acetaminophen (n = 31) or no acetaminophen (n = 31). Median (interquartile range) reduction in creatinine after 72 hours was 23% (37% to 18%) in patients assigned to acetaminophen, versus 14% (29% to 0%) in patients assigned to no acetaminophen (P = .043). This difference in reduction was 37% (48% to 22%) versus 14% (30% to -71%) in patients with hemoglobin ≥45000 ng/mL (P = .010). The proportion with progressing kidney injury was higher among controls (subdistribution hazard ratio, 3.0; 95% confidence interval, 1.1 to 8.5; P = .034). PK-PD analyses showed that higher exposure to acetaminophen increased the probability of creatinine improvement. No patient fulfilled Hy's law for hepatotoxicity. Conclusions: In this proof-of-principle study, acetaminophen showed renoprotection without evidence of safety concerns in patients with severe falciparum malaria, particularly in those with prominent intravascular hemolysis. Clinical Trials Registration: NCT01641289.

Was Cavum Septum Pellucidum the Cause of Intractable Seizure in a 17-Year-Old Boy with Wilson Disease?

BACKGROUND: Cavum septum pellucidum (CSP), which is often found incidentally in a few populations, occasionally becomes symptomatic if enlarged significantly. Wilson disease (WD) is an uncommon autosomal recessive inborn defect in copper metabolism characterized by abnormal accumulation of copper in various tissues, particularly in the liver and the brain. Seizure disorder, although rare both in CSP and WD, may happen in a few patients with either of the conditions. CASE DESCRIPTION: We report a case of 17-year-old boy, a patient with known WD, who developed intractable seizure for a year, which was not controlled with a large amount of antiepileptics. Magnetic resonance imaging showed enlargement of his preexisting CSP, which was small and asymptomatic at the time of diagnosis of WD. His WD was in a state of remission when he developed the seizure disorder. On endoscopic cyst fenestration, he was relieved of the seizure. CONCLUSIONS: Symptomatic CSP is a rare disorder, but the coexistence of WD is even rarer. Endoscopic cyst fenestration is a novel procedure that can be successful in properly selected cases. To the best of our knowledge, CSP associated with WD has not been reported in any English literature. We present this case for its rarity along with a relevant literature review.

Cell-free hemoglobin mediated oxidative stress is associated with acute kidney injury and renal replacement therapy in severe falciparum malaria: an observational study.

BACKGROUND: Intravascular hemolysis is an intrinsic feature of severe malaria pathophysiology but the pathogenic role of cell-free hemoglobin-mediated oxidative stress in severe malaria associated acute kidney injury (AKI) is unknown. METHODS: As part of a prospective observational study, enrolment plasma cell-free hemoglobin (CFH), lipid peroxidation markers (F2-isoprostanes (F2-IsoPs) and isofurans (IsoFs)), red cell deformability, and serum creatinine were quantified in Bangladeshi patients with severe falciparum malaria (n = 107), uncomplicated malaria (n = 80) and sepsis (n = 28). The relationships between these indices and kidney function and clinical outcomes were examined. RESULTS: AKI was diagnosed at enrolment in 58% (62/107) of consecutive patients with severe malaria, defined by an increase in creatinine ≥1.5 times expected baseline. Severe malaria patients with AKI had significantly higher plasma cell-free hemoglobin (geometric mean CFH: 8.8 µM; 95% CI, 6.2-12.3 µM), F2-isoprostane (56.7 pg/ml; 95% CI, 45.3-71.0 pg/ml) and isofuran (109.2 pg/ml; 95% CI, 85.1-140.1 pg/ml) concentrations on enrolment compared to those without AKI (CFH: 5.1 µM; 95% CI, 4.0-6.6 µM; P = 0.018; F2-IsoPs: 27.8 pg/ml; 95% CI, 23.7-32.7 pg/ml; P < 0.001; IsoFs: 41.7 pg/ml; 95% CI, 30.2-57.6 pg/ml; P < 0.001). Cell-free hemoglobin correlated with markers of hemolysis, parasite burden (P. falciparum histidine rich protein 2 (PfHRP2)), and F2-IsoPs. Plasma F2-IsoPs and IsoFs inversely correlated with pH, positively correlated with creatinine, PfHRP2 and fractional excretion of sodium, and were higher in patients later requiring hemodialysis. Plasma F2-IsoP concentrations also inversely correlated with red cell deformability and were higher in fatal cases. Mixed effects modeling including an interaction term for CFH and time showed that F2-IsoPs, IsoFs, PfHRP2, CFH, and red cell rigidity were independently associated with increasing creatinine over 72 h. Multivariable logistic regression showed that admission F2-IsoPs, IsoFs and red cell deformability were associated with the need for subsequent hemodialysis. CONCLUSIONS: Cell-free hemoglobin and lipid peroxidation are associated with acute kidney injury and disease severity in falciparum malaria, suggesting a pathophysiological role in renal tubular injury. Evaluation of adjunctive therapies targeting cell-free hemoglobin-mediated oxidative stress is warranted.

Impact of a structured ICU training programme in resource-limited settings in Asia.

OBJECTIVE: To assess the impact on ICU performance of a modular training program in three resource-limited general adult ICUs in India, Bangladesh, and Nepal. METHOD: A modular ICU training programme was evaluated using performance indicators from June 2009 to June 2012 using an interrupted time series design with an 8 to 15 month pre-intervention and 18 to 24 month post-intervention period. ICU physicians and nurses trained in Europe and the USA provided training for ICU doctors and nurses. The training program consisted of six modules on basic intensive care practices of 2-3 weeks each over 20 months. The performance indicators consisting of ICU mortality, time to ICU discharge, rate at which patients were discharged alive from the ICU, discontinuation of mechanical ventilation or vasoactive drugs and duration of antibiotic use were extracted. Stepwise changes and changes in trends associated with the intervention were analysed. RESULTS: Pre-Training ICU mortality in Rourkela (India), and Patan (Nepal) Chittagong (Bangladesh), was 28%, 41% and 62%, respectively, compared to 30%, 18% and 51% post-intervention. The intervention was associated with a stepwise reduction in cumulative incidence of in-ICU mortality in Chittagong (adjusted subdistribution hazard ratio [aSHR] (95% CI): 0.62 (0.40, 0.97), p = 0.03) and Patan (aSHR 0.16 (0.06, 0.41), p<0.001), but not in Rourkela (aSHR: 1.17 (0.75, 1.82), p = 0.49). The intervention was associated with earlier discontinuation of vasoactive drugs at Rourkela (adjusted hazard ratio for weekly change [aHR] 1.08 (1.03, 1.14), earlier discontinuation of mechanical ventilation in Chittagong (aHR 2.97 (1.24, 7.14), p = 0.02), and earlier ICU discharge in Patan (aHR 1.87 (1.02, 3.43), p = 0.04). CONCLUSION: This structured training program was associated with a decrease in ICU mortality in two of three sites and improvement of other performance indicators. A larger cluster randomised study assessing process outcomes and longer-term indicators is warranted.

Correlation of biomarkers for parasite burden and immune activation with acute kidney injury in severe falciparum malaria.

BACKGROUND: Acute kidney injury (AKI) complicating severe Plasmodium falciparum malaria occurs in up to 40% of adult patients. The case fatality rate reaches 75% in the absence of renal replacement therapy (RRT). The precise pathophysiology of AKI in falciparum malaria remains unclear. Histopathology shows acute tubular necrosis with localization of host monocytes and parasitized red blood cells in the microvasculature. This study explored the relationship of plasma soluble urokinase-type plasminogen activator receptor (suPAR), as a proxy-measure of mononuclear cell activation, and plasma P. falciparum histidine rich protein 2 (PfHRP2), as a measure of sequestered parasite burden, with AKI in severe malaria. METHODS: Admission plasma suPAR and PfHRP2 concentrations were assessed in Bangladeshi adults with severe falciparum malaria (n=137). Patients were stratified according to AKI severity based on admission creatinine clearance. RESULTS: A total of 106 (77%) patients had AKI; 32 (23%), 42 (31%) and 32 (23%) were classified into 'mild, 'moderate' and 'severe' AKI groups, respectively. Plasma suPAR and PfHRP2 concentrations increased with AKI severity (test-for-trend P <0.0001) and correlated with other markers of renal dysfunction. Admission plasma suPAR and PfHRP2 concentrations were higher in patients who later required RRT (P <0.0001 and P=0.0004, respectively). In a multivariate analysis, both increasing suPAR and PfHRP2 were independently associated with increasing urine neutrophil gelatinase-associated lipocalin concentration, a marker of acute tubular necrosis (ß=16.54 (95% CI 6.36-26.71) and ß=0.07 (0.02-0.11), respectively). CONCLUSIONS: Both sequestered parasite burden and immune activation contribute to the pathogenesis of AKI in severe falciparum malaria.

Use of heat of adsorption to quantify amorphous content in milled pharmaceutical powders.

Isothermal calorimetry operated in gas perfusion mode (IGPC) is often used to quantify the amorphous content of pharmaceutical powders. Typically, the calibration line is constructed using the heat of crystallisation as the sample is exposed to high levels of a plasticising vapour. However, since the physical form to which the amorphous fraction crystallises may be dependent on the presence of any crystalline seed, the calibration line is often seen to be non-linear, especially as the amorphous content of the sample approaches 100% w/w. Redesigning the experiment so that the calibration line is constructed with the heat of adsorption is an alternative approach that, because it is not dependent upon crystallisation to a physical form should ameliorate this problem. The two methods are compared for a model compound, salbutamol sulphate, which forms either a hydrate or an anhydrate depending on the amorphous content. The heat of adsorption method was linear between amorphous contents of 0 and 100% w/w and resulted in a detection limit of 0.3% w/w and a quantification limit of 0.92% w/w. The heat of crystallisation method was linear only between amorphous contents of 0 and 80% w/w and resulted in a detection limit of 1.7% w/w and a quantification limit of 5.28% w/w. Thus, the use of heat of adsorption is shown to be a better method for quantifying amorphous contents to better than 1% w/w.

The reliability of the physical examination to guide fluid therapy in adults with severe falciparum malaria: an observational study.

BACKGROUND: Adults with severe malaria frequently require intravenous fluid therapy to restore their circulating volume. However, fluid must be delivered judiciously as both under- and over-hydration increase the risk of complications and, potentially, death. As most patients will be cared for in a resource-poor setting, management guidelines necessarily recommend that physical examination should guide fluid resuscitation. However, the reliability of this strategy is uncertain. METHODS: To determine the ability of physical examination to identify hypovolaemia, volume responsiveness, and pulmonary oedema, clinical signs and invasive measures of volume status were collected independently during an observational study of 28 adults with severe malaria. RESULTS: The physical examination defined volume status poorly. Jugular venous pressure (JVP) did not correlate with intravascular volume as determined by global end diastolic volume index (GEDVI; r(s) = 0.07, p = 0.19), neither did dry mucous membranes (p = 0.85), or dry axillae (p = 0.09). GEDVI was actually higher in patients with decreased tissue turgor (p < 0.001). Poor capillary return correlated with GEDVI, but was present infrequently (7% of observations) and, therefore, insensitive. Mean arterial pressure (MAP) correlated with GEDVI (rs = 0.16, p = 0.002), but even before resuscitation patients with a low GEDVI had a preserved MAP. Anuria on admission was unrelated to GEDVI and although liberal fluid resuscitation led to a median hourly urine output of 100 ml in 19 patients who were not anuric on admission, four (21%) developed clinical pulmonary oedema subsequently. MAP was unrelated to volume responsiveness (p = 0.71), while a low JVP, dry mucous membranes, dry axillae, increased tissue turgor, prolonged capillary refill, and tachycardia all had a positive predictive value for volume responsiveness of ≤50%. Extravascular lung water ≥11 ml/kg indicating pulmonary oedema was present on 99 of the 353 times that it was assessed during the study, but was identified on less than half these occasions by tachypnoea, chest auscultation, or an elevated JVP. A clear chest on auscultation and a respiratory rate <30 breaths/minute could exclude pulmonary oedema on 82% and 72% of occasions respectively. CONCLUSIONS: Findings on physical examination correlate poorly with true volume status in adults with severe malaria and must be used with caution to guide fluid therapy. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT00692627.

Contiguous haemangioblastomas of the brain and spine in a patient of Von Hippel-Lindau disease.

Von Hippel-Lindau (VHL) disease is an inherited, autosomal-dominant syndrome caused by heterozygous germline mutations in the VHL gene, and predisposing to the development of benign and malignant tumours and cysts in multiple organ systems involving eyes, kidneys, pancreas, liver and central nervous system. The responsible tumour suppressor gene for VHL disease is in chromosome 3p25. We are presenting a case of a patient with both cerebellar as well as spinal haemangioblastoma in addition to polycystic pancreas. We operated on both the spinal and the cerebellar haemangioblastomas and the patient had made a very good recovery. We present this case for its rarity along with the literature review.