Changing Landscape of Haemophilus influenzae Meningitis and Implication on Public Health.

Haemophilus influenzae (H. influenzae) has evolved as a prominent pathogen, with nontypeable strains (NTHi) emerging as a leading cause of invasive disease, particularly among the elderly. Since the introduction of Haemophilus influenzae B (Hib) vaccine, invasive infection has shifted from children with Hib to the elderly with NTHi. NTHi affects those primarily with predisposing factors such as an immunocompromised state, CSF leakage, or ENT infections. We present two cases that emphasize the shift of invasive infection, risk factors, and elevated intracranial pressure (ICP) as a complication. Case 1. A 75-year-old female with a sudden onset of weakness and respiratory symptoms deteriorated rapidly. Imaging revealed mastoid effusion and ventriculitis, likely originating from otomastoiditis. Lumber puncture confirmed NTHi. ICU course complicated by elevated ICP prompted repeat lumbar puncture. The patient recovered after 8 days but not near baseline. Case 2. A 50-year-old female with altered mental status, headache, and ear pain exhibited signs of pansinusitis and pseudotumor cerebri. Elevated ICP was evident upon lumbar puncture, and NTHi was isolated in CSF and blood cultures. MRI of the brain showed prominent optic nerve sheaths and transverse sinus arachnoid granulations' concern for underlying pseudotumor cerebri. Repeat lumbar puncture or ventricular drainage was deferred after discussion with neurosurgery. Diabetes was identified as a comorbidity. The patient's condition improved after 14 days of antibiotics and dexamethasone. These cases emphasize the shifting landscape of H. influenzae meningitis, primarily driven by NTHi, especially among the elderly. Although NTHi infections were considered less invasive, recent epidemiology review indicated it as the leading cause of H. influenzae meningitis. With the increasing prevalence of NTHi and its increase in invasive patterns, it is crucial to implement vaccination strategies and develop new vaccines targeting NTHi.

Inpatient thrombophilia workup; does hematology consult prevent unnecessary testing?

Hypercoagulable disorders are best described as a group of acquired and hereditary conditions that increase the risk for the development of thrombi within veins or arteries. In the setting of an unprovoked venous thromboembolism, common practice in the inpatient setting has been further investigation via a thrombophilia workup to establish an underlying cause. Current Hematology-Oncology guidelines argue against inpatient workup as the results rarely influence inpatient management. Following American Society of Hematology guidelines (Middledorp), the current study found that only 15% (11/72) of patients met appropriate criteria for thrombophilia testing. There was no relationship between appropriate thrombophilia testing and diagnosis of thrombophilia or initiation of anticoagulation. There was a relationship between appropriate thrombophilia testing and Hematology-Oncology consultation. This demonstrates the need for expert consultation if thrombophilia testing is being considered. The current study provides more evidence that a strong recommendation against inpatient testing should be made as testing does not aid in diagnosis or change management and is an overutilization of healthcare resources.

Sarcoid-like reaction in malignant melanoma exacerbated with pembrolizumab therapy case report.

Sarcoid Like Reaction (SLR) is a localized non-caseating epithelioid granulomatous reaction seen secondary to certain immunotherapies and malignancies. Invasive melanoma, while being associated with onset of sarcoidosis, has not shown to directly induce SLR in the literature. We present the case of a 68-year-old male with malignant melanoma, who was found to have SLR prior to starting immunotherapy, which worsened while on pembrolizumab. This case highlights the challenge of distinguishing between drug-induced SLR and melanoma-induced SLR, and the implications in terms of management.

Comparison of 3D Hip Joint Kinematics in People with Asymptomatic Pronation of the Foot and Non-Pronation Controls.

BACKGROUND: The impact of asymptomatic pronation on proximal joints during motion has not been well understood, and research on it remains limited. Therefore, the current study determines the effect of asymptomatic pronation of the foot on hip joint kinematics during gait. METHODS: Forty participants were recruited for the study (20 with asymptomatic pronated feet and 20 with non-pronated feet). Foot assessment was conducted by navicular drop and rear-foot angle tests. Hip joint kinematics were measured via MVN Xsens system 3D-motion capture from sagittal, frontal and transverse planes during gait. An independent t-test was used to identify differences in kinematic variables. RESULTS: Both groups were similar in characteristics, and there were no significant differences between the groups in age (P = 0.674) and BMI (P = 0.459). However, there was a significant difference in arch height (P = 0.001) and rear-foot angle (P = 0.001). Our findings showed there were insignificant differences between the asymptomatic pronated foot and non-pronated foot control groups in hip joint kinematics of sagittal (P = 0.618), frontal (P = 0.276), and transverse (P = 0.337) planes during a full gait cycle. CONCLUSION: Patients with asymptomatic pronation of the foot and non-pronation of the foot showed similar movement patterns of hip kinematics in all three planes. The findings of the present study highlight the need for clinicians to consider foot alignment when examining patients with asymptomatic pronation of the foot and non-pronation of the foot.

Characteristics, management and outcomes of critically ill COVID-19 patients admitted to ICU in hospitals in Bangladesh: a retrospective study.

OBJECTIVES: This study aimed to analyze the epidemiological and clinical characteristics of COVID-19 cases and investigate risk factors including comorbidities and age in relation with the clinical aftermath of COVID-19 in ICU admitted cases in Bangladesh. METHODS: In this retrospective study, epidemiological and clinical characteristics, complications, laboratory results, and clinical management of the patients were studied from data obtained from 168 individuals diagnosed with an advanced prognosis of COVID-19 admitted in two hospitals in Bangladesh. RESULTS: Individuals in the study sample contracted COVID-19 through community transmission. 56.5% (n = 95) cases died in intensive care units (ICU) during the study period. The median age was 56 years and 79.2% (n = 134) were male. Typical clinical manifestation included Acute respiratory distress syndrome (ARDS) related complications (79.2%), fever (54.2%) and cough (25.6%) while diabetes mellitus (52.4%), hypertension (41.1%) and heart diseases (16.7%) were the conventional comorbidities. Clinical outcomes were detrimental due to comorbidities rather than age and comorbid individuals over 50 were at more risk. In the sample, oxygen saturation was low (< 95% SpO2) in 135 patients (80.4%) and 158 (93.4%) patients received supplemental oxygen. Identical biochemical parameters were found in both deceased and surviving cases. Administration of antiviral drug Remdesivir and the glucocorticoid, Dexamethasone increased the proportion of surviving patients slightly. CONCLUSIONS: Susceptibility to developing critical illness due to COVID-19 was found more in comorbid males. These atypical patients require more clinical attention from the prospect of controlling mortality rate in Bangladesh.

Whole exome sequencing uncovered highly penetrant recessive mutations for a spectrum of rare genetic pediatric diseases in Bangladesh.

Collectively, rare genetic diseases affect a significant number of individuals worldwide. In this study, we have conducted whole-exome sequencing (WES) and identified underlying pathogenic or likely pathogenic variants in five children with rare genetic diseases. We present evidence for disease-causing autosomal recessive variants in a range of disease-associated genes such as DHH-associated 46,XY gonadal dysgenesis (GD) or 46,XY sex reversal 7, GNPTAB-associated mucolipidosis II alpha/beta (ML II), BBS1-associated Bardet-Biedl Syndrome (BBS), SURF1-associated Leigh Syndrome (LS) and AP4B1-associated spastic paraplegia-47 (SPG47) in unrelated affected members from Bangladesh. Our analysis pipeline detected three homozygous mutations, including a novel c. 863 G > C (p.Pro288Arg) variant in DHH, and two compound heterozygous variants, including two novel variants: c.2972dupT (p.Met991Ilefs*) in GNPTAB and c.229 G > C (p.Gly77Arg) in SURF1. All mutations were validated by Sanger sequencing. Collectively, this study adds to the genetic heterogeneity of rare genetic diseases and is the first report elucidating the genetic profile of (consanguineous and nonconsanguineous) rare genetic diseases in the Bangladesh population.

Clinical characteristics and outcomes of COVID-19 infected diabetic patients admitted in ICUs of the southern region of Bangladesh.

BACKGROUND AND AIMS: Diabetes mellitus is highly prevalent among critical cases of coronavirus disease 2019 (COVID-19) with poor outcomes. This study aimed to describe the clinical characteristics and outcomes of COVID-19 patients with diabetes, admitted in the intensive care unit (ICU) of the southern region of Bangladesh. METHODS: Epidemiological, clinical, laboratory, treatments, complications, and clinical outcomes data were extracted from electronic medical records of 168 COVID-19 patients admitted into ICU of two COVID-19 dedicated hospitals of Chattogram, Bangladesh and compared between diabetes (n = 88) and non-diabetes (n = 80) groups. RESULTS: The prevalence of diabetes was high among 51-70 years old patients. All the diabetic patients had at least one other comorbidity, with a significantly higher incidence of hypertension (53.4% vs 27.5%, P < 0.05). Prevalence of male patients (74/88; 84.1%) was slightly higher among diabetic patients than the non-diabetic patients (60/80; 75%). Even though not significant, Kaplan-Meier survival curve showed that COVID-19 patients with diabetes had a shorter overall survival time than those without diabetes. In subgroup analysis, diabetic patients were classified into insulin-requiring and non-insulin-requiring groups based on their requirement of insulin during the stay in ICU. COVID-19 infected diabetic patients requiring insulin have high risk of disease progression and shorter survival time than the non-insulin required group. CONCLUSIONS: Diabetes is an independent risk factor for the poor prognosis of COVID-19. More attention should be paid to the prevention and prompt treatment of diabetic patients, to maintain good glycaemic control especially those who require insulin therapy.

Aurone: A biologically attractive scaffold as anticancer agent.

Aurones are very simple, promising anticancer lead molecules containing three rings (A, B and C). A very slight structural variation in the aurones elicits diverse affinity and specificity towards different molecular targets. The present review discusses the design, discovery and development of natural and synthetic aurones as small molecule anticancer agents. Detailed structure-activity relationship and intermolecular interactions at different targets are also discussed. Due to their rare occurrence in nature and minimal mention in literature, the anticancer potential of aurones is rather recent but in constant progress.

Scaling Up a Water, Sanitation, and Hygiene Program in Rural Bangladesh: The Role of Program Implementation.

OBJECTIVES: To evaluate whether the quality of implementation of a water, sanitation, and hygiene program called SHEWA-B and delivered by UNICEF to 20 million people in rural Bangladesh was associated with health behaviors and sanitation infrastructure access. METHODS: We surveyed 33 027 households targeted by SHEWA-B and 1110 SHEWA-B hygiene promoters in 2011 and 2012. We developed an implementation quality index and compared the probability of health behaviors and sanitation infrastructure access in counterfactual scenarios over the range of implementation quality. RESULTS: Forty-seven percent of households (n = 14 622) had met a SHEWA-B hygiene promoter, and 47% of hygiene promoters (n = 527) could recall all key program messages. The frequency of hygiene promoter visits was not associated with improved outcomes. Higher implementation quality was not associated with better health behaviors or infrastructure access. Outcomes differed by only 1% to 3% in scenarios in which all clusters received low versus high implementation quality. CONCLUSIONS: SHEWA-B did not meet UNICEF's ideal implementation quality in any area. Improved implementation quality would have resulted in marginal changes in health behaviors or infrastructure access. This suggests that SHEWA-B's design was suboptimal for improving these outcomes.

Role of CNS alpha1-adrenoceptor activity in central fos responses to novelty.

The present study investigated, by use of fos immunohistochemistry, whether the functional activity of alpha(1)-adrenoceptors is elevated during heightened behavioral activity in brain regions shown earlier to contain motoric alpha(1)-receptors. In confirmation, marked c-fos responses that were blocked by an alpha(1)-antagonist (prazosin) were found in four of these brain regions (secondary motor, cingulate, piriform cortices, and nucleus accumbens) of animals exposed to a mildly novel environment (clean cage), which elicits a high degree of sustained exploratory activity. Experimental restriction of exploratory activity in the novel cage by a small enclosure did not reduce the fos responses in these areas, and in fact, enhanced gene expression when carried out in home-caged animals suggesting that the fos response may be more closely associated with the motivation to be active rather than activity itself. Experiments with locally administered alpha(1)-agonists and antagonists in the cortex by reverse dialysis showed that the above mentioned alpha(1)-dependent-fos responses were the result of activation of local alpha(1)-receptors in these brain regions. Unlike the aforementioned brain regions, the fos response of the locus coeruleus was not blocked by prazosin, and this nucleus also showed a marked fos increase to prazosin itself possibly as a compensatory response to the blockade of forebrain alpha(1)-receptors.