Cardiac Changes and Their Reversal Following Curative Surgery in Pheochromocytoma: PheoCard Prospective Cohort Study.

BACKGROUND: Pheochromocytoma and paraganglioma (PPGL) are catecholamine producing tumors of chromaffin cell origin, known to cause varied cardiovascular manifestations from hypertension to myocardial infarction. This study sought to objectively evaluate the cardiac changes in PPGL patients and their reversal following curative surgery. METHODS: The PheoCard study was registered in ClinicalTrials.gov (NCT05082311) and involved 35 consecutive PPGL patients managed as per standard protocol involving alpha blockade followed by curative surgery. They underwent detailed cardiac evaluation using 2D-echocardiography and speckle tracking echocardiography at the time of diagnosis, 7-10 days after alpha blockade, and at 7 days, 3 months, and 6 months after surgical removal. Age- and gender-matched essential hypertensives and healthy individuals (10 in each group) served as two control groups. RESULTS: Patients with PPGLs had significantly higher mean blood pressure, left ventricle end-diastolic dimension and volume (LVEDD, LVEDV), left ventricle end-systolic volume (LVESV), septal wall thickness, LV hypertrophy, lower mean LV ejection fraction (LVEF), early diastolic mitral annular velocity (E/A), decreased amplitude of LV longitudinal strain, and increased circumferential strain (p < 0.001) when compared with the control groups at baseline. After alpha blockade, there was marked reduction in the mean LVEDD, LVEDV, LVESV, and normalization of E/A ratio (p < 0.001) in the PPGL patients. Following curative surgery (normalization of fractionated urinary metanephrines at 7-10 days post-operatively), there was early improvement in all echocardiographic parameters and it continued to improve even at 6 months after surgery. There was marked improvement in the global longitudinal strain as seen on serial speckle tracking echocardiography with recovery of most of the segments of LV depicting the reversal of subclinical endocardial dysfunction (p < 0.001). CONCLUSION: PPGL patients despite normal systolic function have subclinical LV diastolic dysfunction which is reversed after curative surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT05082311.

Assessment of iodine nutrition of schoolchildren in Gonda, India, indicates improvement and effectivity of salt iodisation.

OBJECTIVE: To study the total goitre rate (TGR), urinary iodine concentration (UIC) and salt iodine content among schoolchildren in a previously endemic area for severe iodine deficiency disorder (IDD). DESIGN: Cross-sectional epidemiological study. SETTING: The study was carried out in the Gonda district (sub-Himalayan region) of North India. PARTICIPANTS: Nine hundred and seventy-seven schoolchildren (6-12 years) were studied for parameters such as height, weight, UIC and salt iodine content. Thyroid volume (TV) was measured by ultrasonography to estimate TGR. RESULTS: The overall TGR in the study population was 2·8 % (95 % CI 1·8, 3·8). No significant difference in TGR was observed between boys and girls (3·5 % v. 1·9 %, P = 0·2). There was a non-significant trend of increasing TGR with age (P = 0·05). Median UIC was 157·1 µg/l (interquartile range: 94·5-244·9). At the time of the study, 97 % of salt sample were iodised and nearly 86 % of salt samples had iodine content higher than or equal to 15 part per million. Overall, TGR was significantly lower (2·8 % v. 31·0 %, P < 0·001), and median UIC was significantly higher (157·1 v. 100·0 µg/l, P < 0·05) than that reported in the same area in 2009. CONCLUSIONS: A marked improvement was seen in overall iodine nutrition in the Gonda district after three and a half decades of Universal Salt Iodisation (USI). To sustainably control IDD, USI and other programmes, such as health education, must be continuously implemented along with putting mechanisms to monitor the programme at regular intervals in place.

Low-cost Fluorescein as an Alternative to Radio-colloid for Sentinel Lymph Node Biopsy-a Prospective Validation Study in Early Breast Cancer.

BACKGROUND: Sentinel lymph node biopsy (SLNB) using radio-pharmaceutical (RP) and a blue dye is gold standard for axillary staging in clinically node-negative early breast cancer. High costs and limited availability of RP and/or gamma probe are major deterrents in performing SLNB in developing countries. Fluorescence-guided SLNB can obviate the need for RP and gamma probe. Fluorescein is an inexpensive fluorescent lymphatic tracer. In this study, we compared SLN identification rate (SLN-IR) and false negative rates (FNR) of fluorescein-guided SLNB and radio-guided SLNB using 99mTc-Sulfur-colloid, in isolation, or in combination with methylene blue dye (MBD). METHODS: Sixty-five cN0 early and large operable breast cancer patients underwent validation SLNB using fluorescein (and blue LED light), 99mTc-Sulfur-colloid (and gamma probe) and MBD. Inj Fluorescein 4% was injected, 1 ml each peri-tumoral and sub-areolar five minutes before axillary incision. Axillary dissection was performed irrespective of SLNB histology. The SLN-IR and FNR with various tracers and their combinations were compared. RESULTS: The mean number of SLNs identified was 3.5 ± 1.8 (range 1-6). The SLN-IR using RP alone was 94%, fluorescein alone was 92%, and MBD alone was 82%. The SLN-IR using fluorescein plus MBD combination was 95.4%, compared to 97% using MBD plus RP combination. FNR was 6.3% using fluorescein plus MBD, as well as RP plus MBD combinations. CONCLUSIONS: SLN-IR of > 90% and SLN-FNR of < 10% using fluorescein plus MBD combination are in acceptable range, and are comparable to that of RP plus MBD combination. Fluorescein can replace RP for performing SLNB, in combination with MBD.

The clinical implications of thrombocytopenia in adults with severe falciparum malaria: a retrospective analysis.

BACKGROUND: Thrombocytopenia is a common finding in adults with severe falciparum malaria, but its clinical and prognostic utility is incompletely defined. METHODS: Clinical and laboratory data from 647 adults with severe falciparum malaria were analysed retrospectively to determine the relationship between a patient's platelet count on admission to hospital and their subsequent clinical course. RESULTS: On admission, 614 patients (94.9%) were thrombocytopenic (platelet count <150 × 10(9)/L) and 328 (50.7%) had a platelet count <50 × 10(9)/L. The admission platelet count was inversely correlated with parasite biomass (estimated from plasma PfHRP2 concentrations, rs = -0.28, P = 0.003), the degree of microvascular sequestration (measured with orthogonal polarizing spectral imaging, rs = -0.31, P = 0.001) and disease severity (the number of World Health Organization severity criteria satisfied by the patient, rs = -0.21, P <0.001). Platelet counts were lower on admission in the patients who died (median: 30 (interquartile range 22 to 52) × 10(9)/L versus 50 (34 to 78) × 10(9)/L in survivors; P <0.001), but did not predict outcome independently from other established laboratory and clinical prognostic indices. The 39 patients (6%) with profound thrombocytopenia (platelet count <20 × 10(9)/L) were more likely to die (odds ratio: 5.00, 95% confidence interval: 2.56 to 9.75) than patients with higher platelet counts, but these high-risk patients could be identified more rapidly with simple bedside clinical assessment. The admission platelet count did not reliably identify the 50 patients (7.7%) with major bleeding during the study. CONCLUSIONS: Thrombocytopenia is a marker of disease severity in adults with falciparum malaria, but has limited utility in prognostication, triage and management.

Microvascular obstruction and endothelial activation are independently associated with the clinical manifestations of severe falciparum malaria in adults: an observational study.

BACKGROUND: Microvascular obstruction and endothelial dysfunction have both been linked to tissue hypoperfusion in falciparum malaria, but their relative contributions to the disease's pathogenesis and outcome are unknown. METHODS: Microvascular blood flow was quantified in adults with severe falciparum malaria on their admission to hospital; plasma biomarkers of endothelial function were measured simultaneously. The relationship between these indices and the patients' clinical findings and in-hospital course was examined. RESULTS: Microvascular obstruction was observed in 119/142 (84 %) patients; a median (interquartile range (IQR)) of 14.9 % (6.6-34.9 %) of capillaries were obstructed in patients that died versus 8.3 % (1.7-26.6 %) in survivors (P = 0.039). The proportion of obstructed capillaries correlated with the estimated parasite biomass (rs = 0.25, P = 0.004) and with plasma lactate (rs = 0.38, P <0.0001), the strongest predictor of death in the series. Plasma angiopoietin-2 (Ang-2) concentrations were markedly elevated suggesting widespread endothelial activation; the median (IQR) Ang-2 concentration was 21.9 ng/mL (13.4-29.4 ng/mL) in patients that died versus 14.9 ng/mL (9.8-29.3 ng/mL) in survivors (P = 0.035). Ang-2 concentrations correlated with estimated parasite biomass (rs = 0.35, P <0.001) and plasma lactate (rs = 0.37, P <0.0001). Microvascular obstruction and Ang-2 concentrations were not significantly correlated with each other (rs = 0.17, P = 0.06), but were independently associated with plasma lactate (P <0.001 and P = 0.002, respectively). CONCLUSIONS: Microvascular obstruction and systemic endothelial activation are independently associated with plasma lactate, the strongest predictor of death in adults with falciparum malaria. This supports the hypothesis that the two processes make an independent contribution to the pathogenesis and clinical manifestations of the disease.

Magnetic resonance imaging during life: the key to unlock cerebral malaria pathogenesis?

Understanding the mechanisms underlying the pathophysiology of cerebral malaria in patients with Plasmodium falciparum infection is necessary to implement new curative interventions. While autopsy-based studies shed some light on several pathological events that are believed to be crucial in the development of this neurologic syndrome, their investigative potential is limited and has not allowed the identification of causes of death in patients who succumb to it. This can only be achieved by comparing features between patients who die from cerebral malaria and those who survive. In this review, several alternative approaches recently developed to facilitate the comparison of specific parameters between fatal, non-fatal cerebral malaria and uncomplicated malaria patients are described, as well as their limitations. The emergence of neuroimaging as a revolutionary tool in identifying critical structural and functional modifications of the brain during cerebral malaria is discussed and highly promising areas of clinical research using magnetic resonance imaging are highlighted.

Comparing Leishman and Giemsa staining for the assessment of peripheral blood smear preparations in a malaria-endemic region in India.

BACKGROUND: Microscopy of peripheral blood thin and thick films remains the reference for malaria diagnosis. Although Giemsa staining is most commonly used, the Leishman staining method provides better visualization of the nuclear chromatin pattern of cells. It is less well known whether accuracy of parasitaemia assessment is equally accurate with the latter method. METHODS: Peripheral blood thin and thick smears from consecutive febrile patients admitted to Ispat General hospital, Rourkela, Odhisa, India, were stained with Giemsa and Leishman stain. Methods were compared for species identification, parasite quantification, and ability for identification of alternative diagnoses. RESULTS: Blood films from 1,180 fever patients were compared according to staining method, of which 111 were identified as parasitaemic using Giemsa and 110 with Leishman staining. The Kappa value as a measure of agreement between methods was 0.995 (p < 0.001), and the log10parasitaemia between methods were strongly correlated (r2 = 0.9981). In parasite negative patients, thin smear assessment contributed to making a diagnosis in 276/1,180 (23%) of cases. These assessments were better made in Leishman-stained preparations, especially for the assessment of morphological changes in red and white cells. CONCLUSION: Leishman's staining method for thin and thick smears is a good alternative to Giemsa's stain for identifying Plasmodium parasites. The Leishman method is superior for visualization of red and white blood cell morphology.

Morbidity of chemotherapy administration and satisfaction in breast cancer patients: a comparative study of totally implantable venous access device (TIVAD) versus peripheral venous access usage.

BACKGROUND: This prospective, non-randomized, comparative study evaluated morbidity of chemotherapy administration via a totally implantable venous access device (TIVAD) versus peripheral intravenous access (PIVA), and satisfaction in breast cancer patients in a limited-resource setting. METHODS: Consecutive patients receiving chemotherapy via TIVAD (n = 114) or PIVA (n = 159) were studied. Venous access-related events were recorded. Morbidity and satisfaction with TIVAD or PIVA as perceived by the patients were assessed using a specifically designed questionnaire, which patients filled after 1st cycle of, and after completion of all chemotherapy. RESULTS: Patients in the two groups were of comparable age, body mass index, and disease stage. Acceptance of TIVAD was higher in literate patients. TIVAD did not interfere with sleep or activities in 90 % of patients. The majority (81.2 %) were satisfied with the cosmetic outcome, 91.5 % would have TIVAD re-inserted if the need arose, and 89.6 % would recommend it to others. Non-fatal complications occurred in 16 patients, and TIVAD had to be removed prematurely in five patients. In the PIVA group, 40 % needed multiple needle pricks and 55.8 % developed thrombophlebitis or staining of arms. Drug extravasation and ulceration were suffered by 8.3 and 4.2 %, respectively. However, 78.3 % of patients reported no interference with daily activities and only 26 % would prefer a TIVAD. Those receiving more than six chemotherapy cycles were dissatisfied to a greater extent with PIVA (p < 0.05). CONCLUSIONS: Breast cancer chemotherapy via TIVAD is safe and convenient and results in high satisfaction levels, although it involves additional expenditure. Chemotherapy via PIVA is acceptable, albeit with lower satisfaction, more so in those receiving more than six chemotherapy cycles.

Fluid resuscitation of adults with severe falciparum malaria: effects on Acid-base status, renal function, and extravascular lung water.

OBJECTIVE: To evaluate the efficacy and safety of liberal fluid resuscitation of adults with severe malaria. DESIGN, SETTING, PATIENTS, AND METHODS: Twenty-eight Bangladeshi and Indian adults with severe falciparum malaria received crystalloid resuscitation guided by transpulmonary thermodilution (PiCCO) in an intensive care setting. Systemic hemodynamics, microvascular indices and measures of acidosis, renal function, and pulmonary edema were followed prospectively. RESULTS: All patients were hypovolemic (global end-diastolic volume index<680 mL/m) on enrollment. Patients received a median (range) 3230 mL (390-7300) of isotonic saline in the first 6 hours and 5450 mL (710-13,720) in the first 24 hours. With resuscitation, acid-base status deteriorated in 19 of 28 (68%), and there was no significant improvement in renal function. Extravascular lung water increased in 17 of 22 liberally resuscitated patients (77%); eight of these patients developed pulmonary edema, five of whom died. All other patients survived. All patients with pulmonary edema during the study were hypovolemic or euvolemic at the time pulmonary edema developed. Plasma lactate was lower in hypovolemic patients before (rs=0.38; p=0.05) and after (rs=0.49; p=0.01) resuscitation but was the strongest predictor of mortality before (chi-square=9.9; p=0.002) and after resuscitation (chi-square=11.1; p<0.001) and correlated with the degree of visualized microvascular sequestration of parasitized erythrocytes at both time points (rs=0.55; p=0.003 and rs=0.43; p=0.03, respectively). Persisting sequestration was evident in 7 of 15 patients (47%) 48 hours after enrollment. CONCLUSIONS: Lactic acidosis--the strongest prognostic indicator in adults with severe falciparum malaria--results from sequestration of parasitized erythrocytes in the microcirculation, not from hypovolemia. Liberal fluid resuscitation has little effect on this sequestration and does not improve acid-base status or renal function. Pulmonary edema--secondary to increased pulmonary vascular permeability--is common, unpredictable, and exacerbated by fluid loading. Liberal fluid replacement of adults with severe malaria should be avoided.

Surgical management of organ-contained unilateral pheochromocytoma: comparative outcomes of laparoscopic and conventional open surgical procedures in a large single-institution series.

PURPOSE: Laparoscopic excision is preferred for small non-invasive pheochromocytoma over open approach. Applicability of laparoscopic procedures for large organ-contained pheochromocytoma is unclear. A database of 137 pheochromocytoma patients managed during 1990-2010 was reviewed to compare outcomes of open and laparoscopic procedures for 101 unilateral organ-contained pheochromocytoma patients in this retrospective non-randomized study. PATIENTS AND METHODS: Forty-nine patients underwent open procedures, and 52 underwent laparoscopic procedures. Laparoscopic procedure was converted to open in 19 due to bleeding (n = 12), concern for malignancy (n = 5), hypertensive crisis (n = 1), and equipment failure (n = 1). Outcome measures were compared between open, laparoscopic, and conversion patient groups. RESULTS: Patient groups were well matched for age, gender, BMI, and clinical and pathological characteristics. Mean tumor size was insignificantly larger in the open (7.6 ± 2.7 cm) than the laparoscopic group (6.6 ± 2 cm, p = 0.06). There were no significant differences in periop hemodynamic events. Mean blood loss, blood transfusion and analgesic requirements, and postop ICU and hospital stay were significantly lesser in laparoscopic than open and conversion groups (p < 0.05). There was no periop mortality. Morbidity occurred more frequently in the open (n = 12) than in the laparoscopic group (n = 3). At follow-up (mean, 44 ± 33.7; range, 6-160 months), no patient had recurrent pheochromocytoma. Outcomes in terms of cure of pheochromocytoma and hypertension were not different between the three groups. CONCLUSIONS: Laparoscopic procedures are feasible and as safe and effective as open procedures for patients with organ-contained pheochromocytoma. In a patient cohort where majority of the patients had large (>6 cm) pheochromocytoma, laparoscopic procedures resulted in lesser morbidity and shorter convalescence and provided equal chance for cure of pheochromocytoma and hypertension as conventional open surgical procedures.

The impact of vitamin D status and tumor size on the intraoperative parathyroid hormone dynamics in patients with symptomatic primary hyperparathyroidism.

PURPOSE: The intraoperative parathyroid hormone (IOPTH) monitoring is a useful adjunct for predicting whether a cure has been obtained during parathyroidectomy. We studied the influence of vitamin D status and parathyroid tumor weight on the IOPTH dynamics for predicting a cure in patients with symptomatic primary hyperparathyroidism. METHODS: Fifty-nine primary hyperparathyroidism patients with a single adenoma underwent curative surgery. Patients were grouped according to their serum 25-hydroxy vitamin D levels (deficient, insufficient and sufficient) and tumor weights (small, large and giant). The IOPTH results in patient groups were compared, and the percentage of the IOPTH decrease was examined for a correlation with the serum 25-hydroxy vitamin D level and tumor weight. RESULTS: The sensitivity, specificity and overall accuracy of IOPTH in predicting a cure of hyperparathyroidism were 94.8, 100 and 93.2%, respectively. The percentage decrease in the IOTPH was significantly higher in the vitamin D deficient, compared to the vitamin D sufficient patients (p = 0.012); and in the patients with larger tumors, compared to those with smaller parathyroid tumors (p = 0.02). A statistically significant correlation was found between the percentage decrease in the IOPTH at 10 min post-tumor excision and the serum 25-hydroxy vitamin D level (p = 0.037), but not with the tumor weight (p = 0.208). CONCLUSIONS: The IOPTH can accurately predict a cure in patients with severe primary hyperparathyroidism. The percentage of decrease in the IOPTH is steeper in patients with lower serum 25-hydroxy vitamin D levels and larger parathyroid tumors.

Pre-Operative Selective vs Non-Selective α-Blockade in Pheochromocytoma-Paraganglioma Patients Undergoing Surgery: A Meta-Analysis.

The main objective of this systematic review and meta-analysis was to review, assess and report on the studies that have evaluated selective alpha blockade (SAB) vs. non-selective alpha blockade (NSAB) therapy in patients undergoing surgery for pheochromocytomas and paragangliomas (PPGL). We performed a systematic search of electronic databases. A meta-analysis was conducted to examine the effectiveness of the two blockades. RevMan 5.3 was used for the meta-analysis. Of the eight articles that met the inclusion criteria, there was only one randomized control trial. Meta-analysis showed that there was no significant difference between the groups SAB and NSAB with regard to intra-operative systolic blood pressure (SBP) >160 mm Hg (relative risk (RR) 0.95 [95% CI 0.57, 1.56] P = 0·83) and intra-operative vasopressor requirement (RR 1.10 [95% CI 0.96, 1.26] P = 0·16). Meta-analysis revealed that there was a significant difference between the groups (SAB vs NSAB) with respect to post-operative vasopressor requirement (RR 1.66 [95% CI 1.0, 2.74] P = 0·05). There was no significant difference between the groups with respect to post-operative complications (RR 0.84 [95% CI 0.58, 1.22] P = 0·36). In conclusion, as patients blocked selectively may have a higher incidence of vasodilator requirement intra-operatively, NSAB offers some haemodynamic advantage over SAB. However, NSAB's real clinical benefit cannot be ascertained with the current studies as this difference did not result in any significant advantage over SAB with regard to morbidity or mortality.

Natural Orifice Endoscopic Thyroidectomy via Transoral Vestibular Approach (TOVA): Single Surgeon Experience from North India.

The transoral vestibular approach (TOVA) is the shortest route for endoscopic thyroidectomy (ET) to approach the thyroid and is a totally scar free procedure, hence it has a clear cosmetic advantage not only over conventional open thyroid surgery but also over other remote access approaches for ET like axilla, breast and chest wall approaches. The aim of this study was to evaluate the feasibility, safety and our initial outcomes of TOVA and highlight the advantages of 3D endoscopic equipment in remote access thyroid surgery. We reviewed our prospectively maintained database who underwent ET. 42 patients who fulfilled the stringent inclusion criteria were offered TOVA. We have used novel Trans-vestibular approach with 3D technology for endoscopic thyroid surgery in all cases. Clinico-demographic profile, investigations, operative details, histopathology and postoperative complications and follow-up data were analyzed by using statistical analysis with SPSS19.00 version. Out of 203 ET operated during study period, 42 (20.69%) patients were operated through TOVA. Hemithyroidectomy were performed in all the patients. There were 3 men and 39 women (M:F = 1:13). Mean tumor size was 3.54 ± 1.17 cm. All patients were euthyroid. All patient had cytological diagnosis of Bethesda category II-IV and all underwent hemithyroidectomy. Mean operation time was 107.71 ± 17.60 min and post-operative length of hospital stay was 2.90 ± 1.28 days. Besides magnification, 3D endoscopy provided excellent depth perception which helped in precise dissection in the restricted space and aided in identification and preservation of the two most vital structures i.e. recurrent laryngeal nerve and parathyroid glands. As most of our patients present with larger goitres, not many patients desirous of ET can be offered TOVA. This novel TOVA has fairly stringent inclusion criteria, however it is the only approach which offers completely scarless endoscopic thyroidectomy and should be offered to eligible patients desirous of ET.

Care of inflammatory bowel disease patients during coronavirus disease-19 pandemic using digital health-care technology.

Background and Aim: Although telemedicine is an option for the care of inflammatory bowel disease (IBD) patients during the Coronavirus Disease (COVID)-19 pandemic, its feasibility and acceptability data are scant. Data on the frequency of COVID-19 among patients with IBD, quality of life (QOL), access to health care, psychological stress, and anxiety during the COVID-19 pandemic are scant. Methods: Video/audio consultation for IBD patients was undertaken after a web-based appointment, and data on acceptability, IBD control, Hospital Anxiety Depression Scale (HADS), and World Health Organization Quality of Life questionnaire (WHOQOL-Bref) were obtained electronically. IBD patients were assessed for COVID-19 symptoms or contact history and tested using reverse transcriptase polymerase chain reaction (RT-PCR) on naso- oro-pharyngeal swabs, and data were compared with 16,317 non-IBD controls. Results: Teleconsultation was feasible and acceptable. IBD patients had COVID-19 as frequently as non-IBD controls despite immunosuppressive therapy, possibly due to their awareness and preventive practices. Although the physical, psychological, and social QOL scores during the COVID-19 pandemic were comparable to the prepandemic period, the environmental scores were worse. Psychological tension and interference with work due to pain were lower during the pandemic, which might be influenced by the control of the disease. Conclusions: Teleconsultation is a feasible and acceptable alternative for IBD patients. They had COVID-19 as frequently as non-IBD controls despite a high frequency of immunosuppressive treatment, possibly due to their awareness of the disease and preventive practices. The QOL scores (except the environmental domains) and psychological issues were quite comparable or even better during the COVID-19 pandemic than earlier.

Arterolane, a new synthetic trioxolane for treatment of uncomplicated Plasmodium falciparum malaria: a phase II, multicenter, randomized, dose-finding clinical trial.

BACKGROUND: Drug-resistant Plasmodium falciparum malaria necessitates development of novel drugs for treatment.The present study assessed the efficacy and safety of 3 dose levels of arterolane (RBx 11160), a synthetic trioxolane, for treatment of acute uncomplicated falciparum malaria. METHODS: In this randomized, double-blind, multicenter, parallel-group, dose-finding, phase II trial, 230 patients from 4 centers in Thailand, India, and Tanzania (mainland and Zanzibar) received either 50 mg (n=78), 100mg (n=76), or 200 mg (n=76) of arterolane once daily for 7 days. Patients (aged 13-65 years) with asexual parasite density of 1000-100,000 parasites/microL were included and were followed up for 28 days. The median time to 90% parasite clearance (PC90) was evaluated. RESULTS: The median PC90 was longer in the group receiving the 50-mg dose (19.4 h), compared with the groups receiving the 100-mg dose (12.8 h) and 200-mg dose (12.6 h) (P < .01). The polymerase chain reaction-corrected adequate clinical and parasitological responses on day 28 were 63%, 71%, and 72% for the groups receiving the 50-mg, 100-mg, and 200-mg doses, respectively, by intention-to-treat analysis (odds ratio, 1.55; 95%confidence interval, 0.78-3.06, for comparison of the 200-mg and 50-mg dose groups). Treatment was generally well tolerated. No patient died or experienced any serious adverse event. Mild complaints were reported in <10%of the patients and were similar in the 3 groups. Biochemistry and hematological analyses did not show any signof drug toxicity in any patient. CONCLUSION: Arterolane at daily doses of 100 and 200 mg is a rapidly acting, effective, and safe synthetic antimalarial drug, which may potentially represent an alternative to artemisinin derivatives in antimalarial combination therapy. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00362050.

A simple score to predict the outcome of severe malaria in adults.

BACKGROUND: World Health Organization treatment guidelines recommend that adults with severe malaria be admitted to an intensive care unit (ICU). However, ICU facilities are limited in the resource-poor settings where most malaria occurs. Identification of patients at greater risk of complications may facilitate their triage and resource allocation. METHODS: With use of data from a trial conducted in Southeast Asia (n=868), a logistic regression model was built to identify independent predictors of mortality among adults with severe malaria. A scoring system based on this model was tested in the original dataset and then validated in 2 series from Bangladesh (n=188) and Vietnam (n=292). RESULTS: Acidosis (base deficit) and cerebral malaria (measured as Glasgow Coma Score) were the main independent predictors of outcome. The 5-point Coma Acidosis Malaria (CAM) score was simply derived from these 2 variables. Mortality increased steadily with increasing score. A CAM score <2 predicted survival with a positive predictive value (PPV) of 95.8% (95% confidence interval [CI], 93%- 97.7%). Of the 14 of 331 patients who died with a CAM score <2, 11 (79%) had renal failure and death occurred late after hospital admission (median, 108 h; range, 40-360 h). Substitution of plasma bicarbonate as the measure of acidosis only slightly reduced the prognostic value of the model. Use of respiratory rate was inferior, but a score <2 still predicted survival with a PPV of 92.2% (95% CI, 89.1%-94.7%). CONCLUSIONS: Patients with a CAM score <2 at hospital admission may be safely treated in a general ward, provided that renal function can be monitored.

Uncertainty quantification based cloud parameterization sensitivity analysis in the NCAR community atmosphere model.

Using uncertainty quantification techniques, we carry out a sensitivity analysis of a large number (17) of parameters used in the NCAR CAM5 cloud parameterization schemes. The LLNL PSUADE software is used to identify the most sensitive parameters by performing sensitivity analysis. Using Morris One-At-a-Time (MOAT) method, we find that the simulations of global annual mean total precipitation, convective, large-scale precipitation, cloud fractions (total, low, mid, and high), shortwave cloud forcing, longwave cloud forcing, sensible heat flux, and latent heat flux are very sensitive to the threshold-relative-humidity-for-stratiform-low-clouds ([Formula: see text] and the auto-conversion-size-threshold-for-ice-to-snow [Formula: see text] The seasonal and regime specific dependence of some parameters in the simulation of precipitation is also found for the global monsoons and storm track regions. Through sensitivity analysis, we find that the Somali jet strength and the tropical easterly jet associated with the south Asian summer monsoon (SASM) show a systematic dependence on [Formula: see text] and [Formula: see text]. The timing of the withdrawal of SASM over India shows a monotonic increase (delayed withdrawal) with an increase in [Formula: see text]. Overall, we find that [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text] are the most sensitive cloud parameters and thus are of high priority in the model tuning process, in order to reduce uncertainty in the simulation of past, present, and future climate.

Fungating Breast Cancer: Experience in Low and Middle Income Country.

Fungating breast cancer (FBC) is a rare entity in developed nations. But this occurrence is not uncommon in our country. The aim of this study was to review clinico-pathologic profile and outcomes of FBC in a developing country. This retrospective study consisted of patients with FBC managed at our institute (Jan 2005-Dec 2015). Clinico-pathologic profile, management details, and outcomes were analyzed. The Kaplan-Meier method was used to determine overall survival (OS). Log-rank test was performed to compare survival in various subgroups. Seventy-nine patients were detected to have FBC constituting 3.3% of all breast cancers and 24.8% of those having T4b lesions. Mean age of the patients was 55 + 11 years. Ninety-six percent were women and 67% belonged to rural areas. A total of 75% women were postmenopausal. Mean duration of lump was 16 + 11 months. The mean tumor size was 8+ 2 cm. Eighty-seven percent had axillary lymph node involvement and 42% distant metastases. Fifty-eight percent (n = 46) patients had stage III and 42% (n = 33) stage had IV tumors. Hormone receptor (HR) positivity was noted in 44% (n = 35) and HER2/neu overexpression in 39% (n = 31) tumors, whereas 32% (n = 25) were triple negative. Overall, 95% (n = 75) of patients received chemotherapy, 91% (n = 72) patients underwent mastectomy, and 76% (n = 60) loco-regional radiotherapy. Median duration of follow-up was 40 (2-93) months. Median survival was 36 months, and 5-year OS was 40%. Except for stage (53% vs 22%, p = 0.005), no other factor influenced OS. Multimodality therapy in FBS results in good symptom palliation and comparable survival to stage III and IV patients without fungating tumors.

Advances in the management of cerebral malaria in adults.

PURPOSE OF REVIEW: Cerebral malaria continues to be a substantial cause of death and disability worldwide. Although many studies deal with cerebral malaria in children, only very few pertain to adults. Presence of multiorgan failure makes the prognosis poor. Various mechanisms in the pathogenesis of cerebral malaria and the role of adjuvant therapy will be discussed. RECENT FINDINGS: Artemisinin-based therapies have improved antiparasitic treatment, but in-hospital mortality still remains high, as do neurological sequelae. Several recent studies have given new insights in the pathophysiology of cerebral malaria particularly the role of immune mechanisms in disease progression. Recent findings have identified several potential candidates for adjuvant neuroprotective treatment. Recombinant human erythropoietin has shown beneficial effect in experimental cerebral malaria and will soon enter into large clinical trials. SUMMARY: Advances have been made in terms of antiparasitic treatment, but the identification of a well tolerated and effective adjuvant treatment to increase survival and reduce brain damage is still pending. The search for new approaches is a major challenge, not least of which is that mechanisms of malaria pathogenesis remain incompletely understood. The paper reviews newer information on pathogenesis and strategies in the management of cerebral malaria in adults.

Laparoscopic adrenalectomy for Conn's syndrome: report of the initial six cases.

We report our experience with the initial six cases of transperitoneal laparoscopic adrenalectomy for primary hyperaldosteronism (Conn's syndrome). This is the first report from India of such a series. From 1997 to 2002, 6 patients with primary hyperaldosteronism (Conn's syndrome) were referred to the Department of Endocrine Surgery and underwent laparoscopic adrenalectomy through the transperitoneal approach. In all patients, the adrenal gland and the adenoma were successfully removed laparoscopically, and all patients were normokalemic and normotensive in the first follow-up after 6 months. Laparoscopic adrenalectomy is a feasible option in cases of hyperaldosteronism. In our series, both hypertension and hypokalemia improved in all