Reference radiologic measurements for the assessment of tibial pilon fractures

Objectives: The management of pilon fractures is a challenge and the outcome depends on multiple factors, one of which is the quality of reduction. In the literature, there is no assessment of anatomical reduction in pilon fractures. We also lack standard radiological parameters in large patient groups to measure the reduction. The main aim of this analysis was to define normal standard radiological values and identify potential specific types of ankle joint morphology (morphotypes) that might deserve special attention intraoperatively. Methods: We analyzed data of 103 healthy contralateral ankles collected within an observational and prospective multicenter study about tibial pilon fractures. We divided the patients according to their height into two groups, measured 11 radiological parameters, and compared them with each other and the literature. In addition, using cluster analysis, we could identify three morphotypes. Results: There is a statistically significant difference between the two groups in the lengths of three parameters: Mortise width, medial clear space, and length of the lateral malleolus, but not in the angles. The three morphotypes differ only in body mass index and the length of the lateral malleolus. Conclusion: Reference values from the literature are insufficient to assess a reduction after open reduction and internal fixation of tibial pilon fractures because they depend on the height. This does not apply to angles because they are independent of height. For clinical practice, a radiological control of the contralateral healthy ankle gives the best information about the reduction quality and should always be done, especially in normal weight males.

Role of micro-RNA132 and its long non coding SOX2 in diagnosis of lupus nephritis

Background The skin and the kidney are commonly affected in systemic lupus erythematosus (SLE) with similar molecular mechanisms. Although clinical indicators of renal injury in SLE are fairly uncontroversial, few biomarkers are reliable. The role of micro-RNAs (mi-RNAs) in lupus nephritis (LN) pathogenesis has been investigated to help in early diagnosis. Purpose The aim of work is to evaluate miRNA132 and SOX2 expressions in SLE Egyptian patients; with and without nephritis, and the relation between miRNA132 and its long non-coding gene SOX2 in both patients groups. Research Design This is a case-control study involving 100 SLE patients with and without LN (LN and non-LN groups), and 50 age-and sex-matched healthy controls. The study was carried out to detect miRNA132 and SOX2 expression by quantitative Real-Time Polymerase chain reaction methods. The SLE disease activity index (SLEDAI) was assessed. Results SLEDAI increased in LN compared to non-LN. Micro-RNA132 expression was significantly increased in patient groups compared to controls ( p<0.01) and increased in LN more than non-LN group ( p<0.001). SOX2 significantly decreased in patient groups compared to controls ( p<0.001), and was more in LN compared to non-LN group ( p<0.001). There was a negative correlation between miRNA132 and SOX2 expression in both patient groups ( p<0.001). Conclusion miRNA132 and SOX2 may play a role in SLE activity and help in the early non-invasive diagnosis of LN.

Acetazolamide modulates intracranial pressure directly by its action on the cerebrospinal fluid secretion apparatus

Elevated intracranial pressure (ICP) is observed in many neurological pathologies, e.g. hydrocephalus and stroke. This condition is routinely relieved with neurosurgical approaches, since effective and targeted pharmacological tools are still lacking. The carbonic anhydrase inhibitor, acetazolamide (AZE), may be employed to treat elevated ICP. However, its effectiveness is questioned, its location of action unresolved, and its tolerability low. Here, we employed in vivo and ex vivo approaches to reveal the efficacy and mode of action of AZE in the rat brain. The drug effectively reduced the ICP, irrespective of the mode of drug administration and level of anaesthesia. The effect occurred via a direct action on the choroid plexus and an associated decrease in cerebrospinal fluid secretion, and not indirectly via the systemic action of AZE on renal and vascular processes. Upon a single administration, the reduced ICP endured for approximately 10 h post-AZE delivery with no long-term changes of brain water content or choroidal transporter expression. However, a persistent reduction of ICP was secured with repeated AZE administrations throughout the day. Future specific targeting of choroidal carbonic anhydrases may limit the systemic side effects, and therefore enhance the treatment tolerability and effectiveness in select patient groups experiencing elevated ICP.

Bacterial biofilms predominate in both acute and chronic human lung infections

BackgroundA basic paradigm of human infection is that acute bacterial disease is caused by fast growing planktonic bacteria while chronic infections are caused by slow-growing, aggregated bacteria, a phenomenon known as a biofilm. For lung infections, this paradigm has been thought to be supported by observations of how bacteria proliferate in well-established growth media in the laboratory—the gold standard of microbiology.ObjectiveTo investigate the bacterial architecture in sputum from patients with acute and chronic lung infections.MethodsAdvanced imaging technology was used for quantification and direct comparison of infection types on fresh sputum samples, thereby directly testing the acute versus chronic paradigm.ResultsIn this study, we compared the bacterial lifestyle (planktonic or biofilm), growth rate and inflammatory response of bacteria in freshly collected sputum (n=43) from patient groups presenting with acute or chronic lung infections. We found that both acute and chronic lung infections are dominated by biofilms (aggregates of bacteria within an extracellular matrix), although planktonic cells were observed in both sample types. Bacteria grew faster in sputum from acute infections, but these fast-growing bacteria were enriched in biofilms similar to the architecture thought to be reserved for chronic infections. Cellular inflammation in the lungs was also similar across patient groups, but systemic inflammatory markers were only elevated in acute infections.ConclusionsOur findings indicate that the current paradigm of equating planktonic with acute and biofilm with chronic infection needs to be revisited as the difference lies primarily in metabolic rates, not bacterial architecture.

Age and injury size influence the magnitude of fecal dysbiosis in adult burn patients

Clinical studies have demonstrated that age ≥ 50 years old is an independent risk factor associated with poor prognosis after burn injury, the second leading cause of traumatic injuries in the aged population. While mechanisms driving age-dependent post-burn mortality are perplexing, changes in the intestinal microbiome however may contribute to the heightened, dysregulated systemic response seen in aging burn patients. The fecal microbiome from 22 patients admitted to a verified burn center from July 2018 to February 2019 were stratified based on age of 50 years and total burn surface area (TBSA) size of ≥10%. Significant differences (P = 0.014) in overall microbiota community composition (i.e., beta diversity) were measured across the four patient groups, young &lt;10% TBSA, young ≥10% TBSA, older &lt;10% TBSA, and older ≥10% TBSA. Differences in beta diversity were driven by %TBSA (P = 0.013) and trended with age (P = 0.087). Alpha diversity components, richness, evenness, and Shannon diversity were measured. We observed significant differences in bacterial species evenness (P = 0.0023) and Shannon diversity (P = 0.0033) between the groups. There were significant correlations between individual bacterial species and levels of SCFA. Specifically, levels of fecal butyrate correlated with the presence of Enterobacteriaceae, an opportunistic gut pathogen, when elevated in burn patients lead to worsen outcomes. Overall, our findings reveal that age-specific changes in the fecal microbiome following burn injuries may contribute to immune system dysregulation in patients with varying TBSA burns and potentially lead to worsen clinical outcomes with heightened morbidity and mortality.

Hearing loss: Conductive versus sensorineural

Hearing loss has a significant impact on quality of life, and may even compromise an individual’s ability to work and their safety – we use our hearing to constantly detect and react to environmental hazards around us. Hearing loss can have a profound impact on a person’s life. This is especially true for certain patient groups. For instance, the elderly, and those with co-existing problems that affect their ability to communicate (such as dementia, cerebrovascular disease or psychiatric disorders). Even those without co-morbidities suffer the burden of disease where communication is impaired: the young who are developing their speech and language skills and adults with language barriers or other impediments to their speech. The hearing apparatus is made up of conductive and sensorineural pathways, which may be affected by pathology, leading to deafness. This article describes the aetiology of conductive and sensorineural deafness, details the relevant clinical assessment and outlines management strategies in community practice.

GENDER AND REGIONAL DISPARITIES IN EMERGENCY ARRHYTHMIA PROCEDURES DURING COVID-19 LOCKDOWN

Objectives: Worldwide reduction in emergency procedures has been observed during the current COVID-19 pandemic. The effects of the pandemic and its associated lockdown on arrhythmia related emergency procedures is not known. This study was done to see the effects of the COVID-19 pandemic lockdown on provision of emergency arrhythmia procedures and to identify vulnerable patient groups that may be disproportionately affected during lockdown. Methodology: Data for patients requiring emergency intracardiac devices including temporary and permanent pacemakers was collected from three public sector hospitals of Sindh, Pakistan, for the COVID-19 lockdown period of March to May 2020. This was compared to the data for the same period for 2019. Results: Patients presenting during lockdown decreased by 32.8% (from 250 to 168) compared to the same period without lockdown. The decline was across all emergency procedures considered. There was a more than fivefold reduction in the number of patients in patients from outside the metropolitan area of the hospital (64.3%) compared to those residing within the city (12.5%) (p=0.001). There was a trend showing women to be more effected, with the percentage decline in women being statistically significant in the rural setting (-93.8% vs. -52.9%, p=0.043). All age groups were equally affected (p=0.152). Conclusion: A marked reduction in the number of patients who presented for emergency intra cardiac devices and TPM procedures was seen during COVID-19 lockdown. The patients who presented from outside the city of the hospital and women in rural setting were significantly more effected.

Patient Centricity Driving Formulation Innovation: Improvements in Patient Care Facilitated by Novel Therapeutics and Drug Delivery Technologies

Innovative formulation technologies can play a crucial role in transforming a novel molecule to a medicine that significantly enhances patients’ lives. Improved mechanistic understanding of diseases has inspired researchers to expand the druggable space using new therapeutic modalities such as interfering RNA, protein degraders, and novel formats of monoclonal antibodies. Sophisticated formulation strategies are needed to deliver the drugs to their sites of action and to achieve patient centricity, exemplified by messenger RNA vaccines and oral peptides. Moreover, access to medical information via digital platforms has resulted in better-informed patient groups that are requesting consideration of their needs during drug development. This request is consistent with health authority efforts to upgrade their regulations to advance age-appropriate product development for patients. This review describes formulation innovations contributingto improvements in patient care: convenience of administration, preferred route of administration, reducing dosing burden, and achieving targeted delivery of new modalities.

Perspectives and Expertise in Establishing a Therapeutic Drug Monitoring Programme for Challenging Childhood Cancer Patient Populations

The utility of Therapeutic Drug Monitoring (TDM) in the setting of childhood cancer is a largely underused tool, despite the common use of cytotoxic chemotherapeutics. While it is encouraging that modern advances in chemotherapy have transformed outcomes for children diagnosed with cancer, this has come at the cost of an elevated risk of life-changing long-term morbidity and late effects. This concern can limit the intensity at which these drugs are used. Widely used chemotherapeutics exhibit marked inter-patient variability in drug exposures following standard dosing, with fine margins between exposures resulting in toxicity and those resulting in potentially suboptimal efficacy, thereby fulfilling criteria widely accepted as fundamental for TDM approaches. Over the past decade in the UK, the paediatric oncology community has increasingly embraced the potential benefits of utilising TDM for particularly challenging patient groups, including infants, anephric patients and those receiving high dose chemotherapy. This has been driven by a desire from paediatric oncologists to have access to clinical pharmacology information to support dosing decisions being made. This provides the potential to modify doses between treatment cycles based on a comprehensive set of clinical information, with individual patient drug exposures being used alongside clinical response and tolerability data to inform dosing for subsequent cycles. The current article provides an overview of recent experiences of conducting TDM in a childhood cancer setting, from the perspectives of the clinicians, scientists and pharmacists implementing TDM-based dosing recommendations. The ongoing programme of work has facilitated investigations into the validity of current approaches to dosing for some of the most challenging childhood cancer patient groups, with TDM approaches now being expanded from well-established cytotoxic drugs through to newer targeted treatments.

Remdesivir for Covid-19 pneumonia in patients with severe chronic kidney disease: Case series and review of the literature

Remdesivir was the first antiviral agent to receive FDA authorization for severe COVID-19 management, which restricts its use with severe renal impairment due to concerns that active metabolites might accumulate, causing renal toxicities. With limited treatment options, available evidence on such patient groups is important to assess for future safety.