Pneumocystis jirovecii Pneumonia Complicated by Pneumomediastinum: A Case Report.

Pneumomediastinum refers to the presence of air in the mediastinum (the space in the chest between the lungs). It can arise from various etiologies, including trauma, esophageal perforation, infections, medical procedures, or underlying lung diseases. Pneumocystis jirovecii pneumonia (PJP) is a common opportunistic infection seen in immunocompromised individuals, especially those with HIV/AIDS. Pneumomediastinum is a rare but serious complication of PJP that occurs in immunosuppressed patients, leading to significant morbidity and mortality. We present a rare case of pneumomediastinum caused by P. jirovecii pneumonia in an AIDS patient.

Streptococcus agalactiae Infective Endocarditis in a Young Immunocompetent Male.

Group B Streptococcus endocarditis is a rare but serious condition, characterized by the infection of heart valves and associated with a high mortality rate. The emergence of antibiotic-resistant strains adds complexity to therapeutic strategies, emphasizing the importance of tailored antibiotic regimens and surgical interventions when indicated. Early diagnosis and multidisciplinary care are essential in improving patient outcomes. A 22-year-old male patient with no comorbidities was admitted with a thromboembolic stroke. MRI brain showed bilateral cerebral and cerebellar multifocal acute nonhemorrhagic infarcts. He was found to have Streptococcus agalactiae bacteremia, and infective mitral valve endocarditis. He underwent mitral valve replacement and IV antibiotic treatment with a successful outcome.

Hathewaya limosa Empyema: A Case Report.

Hathewaya limosa, an anaerobic bacterium, has been associated with various infections, including prosthetic valve endocarditis, although its role in empyema remains uncommon. This abstract presents a case report of a patient diagnosed with H. limosa empyema, highlighting the clinical presentation, diagnostic challenges, and successful treatment strategies. The case underscores the importance of considering unusual pathogens in the context of empyema. We discuss the clinical management, microbiological identification, and outcomes of this rare infection to contribute valuable insights for healthcare practitioners encountering similar cases.

A Case of Acupuncture Induced Pneumothorax.

With various forms of alternative medicinal practices gaining popularity, there is an increase in complications arising from these practices. Acupuncture, which originated in China, and now practiced worldwide as a form of traditional medicine, is generally considered safe; however, rare life-threatening complications can occur following its practice. Here we present the case of a 63-year-old male who presented to the emergency department with symptoms suggestive of pneumothorax. Upon further history, the patient disclosed that he had recently undergone acupuncture treatment for chronic elbow pain.

In Vivo Emergence of Pandrug-Resistant Acinetobacter baumannii Strain: Comprehensive Resistance Characterization and Compassionate Use of Sulbactam-Durlobactam.

The treatment of patients with infection secondary to carbapenem-resistant Acinetobacter baumannii with emerging cefiderocol resistance remains challenging and unclear. We present a case of in vivo emergence of pandrug-resistant A baumannii that was successfully treated with the compassionate use of investigational sulbactam-durlobactam-based antibiotic regimen. We also performed a longitudinal genomic analysis of the bacterial isolates and showed the development of resistance and genetic mutations over time.

Cardiopulmonary Phenotypes of Post Acute Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2: A Narrative Review.

The acute effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are well known; however, the long-term cardiopulmonary effects are less well characterized. The phenotypic expression of acute infection is heterogeneous, ranging from a complete absence of symptoms to shock, multisystem organ failure, and death. Patients with severe or critical coronavirus disease (COVID-19) who survive their initial illness can require a prolonged period of recovery lasting weeks to months. This specific patient group is part of a larger and even more heterogeneous group of patients who initially experience mild-to-moderate symptoms that fail to resolve over time. Collectively, patients recovering from severe or critical COVID-19 and those who continue to experience symptoms following a lower acuity infection are considered to have Post Acute Sequalae of SARS-CoV-2 infection (PASC). Using prognostic factors like myocardial infarction, myocarditis, pulmonary embolism, acute respiratory distress syndrome, need for mechanical ventilation or extracorporeal membrane oxygenation, and advanced pharmaceutical therapies that primarily occur or are instituted in the acute phase of illness one can begin to develop a taxonomy or corpus of PASC in its varied forms.

Syncope Following Treatment of UTI: A Case of Acute Hemolytic Anemia, Methemoglobinemia and Acute Renal Dysfunction Following Phenazopyridine Use in a Patient With G6PD Deficiency.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive genetic disorder which commonly affects males. It is due to a defect in the red blood cell enzyme, G6PD. Lack of G6PD makes the RBCs vulnerable to oxidant stress resulting in hemolysis. The severity of hemolytic anemia varies among individuals with G6PD deficiency. Here we present a case of an 80-year-old man admitted with syncope and jaundice. He was treated with phenazopyridine for a UTI 2 weeks ago. Subsequent investigation revealed G6PD deficiency as well as methemoglobinemia. Historically, phenazopyridine has been associated with causing methemoglobinemia and triggering hemolysis in G6PD deficient individuals. However, only a few cases have been reported in the last 60 years, making it a very rare occurrence.

Challenging Case of Transcatheter Mitral Valve-in-Valve-in-Valve Replacement.

BACKGROUND A 39-year-old man with a complex valvular history of recurrent methicillin-resistant Staphylococcus aureus endocarditis with 2 surgical mitral valve replacements (in 2016 and 2017) followed by transcatheter mitral valve replacement (in 2019) presented with orthopnea, paroxysmal nocturnal dyspnea, chest pain, cough, and progressively worsening dyspnea on exertion. CASE REPORT Extensive workup was performed, including transesophageal echocardiogram, which revealed a malfunctioning, severely stenotic bioprosthetic valve. Left and right heart catheterization revealed mild non-obstructive coronary artery disease and severe pulmonary hypertension. Given the patient's complex medical history, he was deemed to be at an elevated risk for repeat sternotomy and repeat valve replacement surgery. Therefore, he underwent a percutaneous transcatheter mitral valve replacement with a 26-mm SAPIEN 3 Edwards valve placed within the previous 29-mm SAPIEN valve. Post-procedural imaging revealed a well-placed valve with an improved mitral valve gradient. CONCLUSIONS This is one of the few rare cases of mitral valve-in-valve via a transcatheter mitral valve replacement approach with successful deployment of a SAPIEN 3 tissue heart valve. The patient experienced significant reversal of heart failure symptoms and improved exertional tolerance following deployment of the valve and was eventually discharged home in a stable condition.

Development of myocarditis and pericarditis after COVID-19 vaccination in children and adolescents: A systematic review.

Myocarditis and pericarditis have been reported after COVID-19 vaccine administration in children and adolescents, raising the concern about their possible association with these vaccines. The objective was to explore the incidence, clinical presentation, and association of myocarditis and pericarditis with COVID-19 vaccines in children and adolescents. We conducted a systematic literature search on three databases, that is, Cochrane, MEDLINE/PubMed, and EMBASE from inception till March 2022. A total of three case reports, four case series, and six observational studies were included in the review. For case reports and case series, the mean age of the patients was 17.4 years, with 96.9% being male. Chest pain (n = 31, 93.9%), fever (n = 18, 54.5%), myalgias (n = 15, 45.4%) and headache (n = 9, 27.2%) were the most common presentations. Out of 33 patients, 32 (96.9%) of patients received Pfizer-BioNTech whereas only one (3.03%) received Moderna (mRNA 1273). Clinical investigations revealed ST elevation (n = 32, 97%), and elevated CRP (n = 9, 27.2%) and cardiac troponin (n = 29, 87.8%). The pooled incidence of myocarditis and pericarditis from observational studies was (0.00063%) and (0.000074%) %, respectively. Myocarditis and pericarditis in children and adolescents after the COVID-19 vaccines were more prevalent among males and more commonly observed after the second dose of Pfizer. Though the overall incidence was low, however, the clinicians should consider myocarditis and pericarditis as probable diagnosis when encountering young patients, with a history of vaccine administration, presenting with suggestive findings.

Third-Degree Heart Block in COVID-19 Pneumonia Complicated by Methicillin-Resistant Staphylococcus Aureus (MRSA) Bacteremia. A Case Report and Review of Literature.

Coronavirus disease 2019 (COVID-19) burden has been identified to cause multiorgan damage. Respiratory compromise is still one of the most common presentations, but cardiac injuries like myocardial injury, ischemia, and conduction abnormalities are also becoming prevalent. We present a case of an 87-year-old male with a history of dementia, type 2 diabetes mellitus, hypertension, chronic kidney disease, and a left kidney transplant hospitalized for respiratory distress and generalized tonic-clonic seizures. He was bradycardic to 27 beats per minute, hypotensive with mean arterial pressure <60 mm Hg. An electrocardiogram (EKG) depicted a high-grade atrioventricular block (AV-block). The transvenous pacemaker was placed via femoral access and tested positive for COVID-19. Work-up was done to rule out possible causes of bradycardia, like hypothyroidism, ischemia, AV nodal blocking agents, and drug-induced bradycardia was negative. His hospital stay got complicated by methicillin-resistant staphylococcus aureus (MRSA) pneumonia leading to empyema and bacteremia. Unfortunately, being critically ill, the family opted for comfort measures, and he passed away. Our clinical vignette signifies cardiovascular complications in COVID-19 patients are associated with poor outcomes if not addressed. The conduction abnormalities in patients with intact cardiac structure and function are becoming more common in the setting of COVID infection. Assessment with serial EKGs and cardiac monitoring might be essential as patients can develop AV blocks at any point of the disease.

Ventricular Tachycardia or Fibrillation Storm in Coronavirus Disease.

Ventricular tachycardia (VT) or ventricular fibrillation (VF) storm associated with severe acute respiratory syndrome coronavirus 2 infection is a potentially fatal complication; the correlation of these 2 disorders, however, has not been well studied. This retrospective case series examined outcomes of 2 patients who were admitted for repeated implantable cardioverter-defibrillator shocks with or without syncope and observed to have VT/VF storms with COVID-19. Mechanisms of VT/VF storms in COVID-19 are multifactorial including myocarditis, systemic inflammation, hyperadrenergic state, hemodynamic instability, hypoxia, acidosis, and proarrhythmic drugs. A higher incidence of VT/VF storm is observed in patients with comorbidities and those requiring critical care, with some studies reporting increased mortality. In our cohort, 1 of the 2 patients succumbed to the complications from COVID-19, and the other patient was discharged to home in stable condition. Monitoring of life-threatening arrhythmias in the setting of COVID-19 may need to be adopted to prevent morbidity and mortality.

Efficacy of Magnesium Sulfate in Addition to Melatonin Therapy in Neonates With Hypoxic-Ischemic Encephalopathy.

BACKGROUND: One of the most important causes of neonatal deaths in developing nations is birth asphyxia. Though the probability of a complete recovery is very low, hypoxic-ischemic encephalopathy (HIE) associated with asphyxia can be managed with multiple treatment options. The study evaluated the efficacy of the addition of magnesium sulfate (MgSO4) to melatonin therapy in neonates with HIE. METHODOLOGY: A prospective, observational study was conducted in the department of neonatal intensive care, Pakistan Institute of Medical Sciences Hospital, Islamabad, Pakistan from October 2020 to March 2021. All neonates with an Appearance, Pulse, Grimace, Activity, and Respiration (APGAR) score of less than five at five minutes, umbilical blood pH of less than 7.0, and moderate neonatal encephalopathy as detected on the modified Sarnat score which is a clinical tool used for the assessment of the severity of HIE were included in the study. Neonates with congenital abnormalities, intrauterine growth retardation, neonatal sepsis, and infants born to mothers with diabetes mellitus type 2 were excluded from the study. The infants were randomly assigned to either of the groups, i.e., i) group 1 included neonates who were administered at least three doses of magnesium sulfate (MgSO4) infusion in addition to melatonin, or ii) group 2 included neonates who were administered melatonin only. Blood samples of all neonates were evaluated and compared between the two groups. RESULTS: A total of 90 neonates with HIE were included in the study. There was a predominance of female neonates. The mean ages of babies in group 1 and group 2 were 37.2 ± 0.43 and 37.3 ± 0.59 weeks, respectively. The mean weight on the term was 2.88 ± 0.11 and 2.89 ± 0.10, respectively. The Apgar score at 5 mins in group 1 was 1.73 ± 0.81 while in group 2, 1.82 ± 0.94. It was found that there was a more significant improvement in pH after 3 days and after one week of treatment in group 1 as compared to group 2. The mean pH in babies after three days of intervention was 7.23 ± 0.03 in group 1 which was significantly better than group 2 (p<0.0001). After seven days, the mean normalized to 7.39 ± 0.04 in group 1 (p < 0.0001). It was found that in patients in group 1, the mortality was lower than in group 2 (p < 0.0001). CONCLUSION: HIE patients who were administered melatonin in combination with magnesium sulfate yielded better patient outcomes. Thus, it was concluded that the use of magnesium sulfate as dual therapy with melatonin improved patient outcomes for HIE. However, it is recommended that similar studies are conducted with a wider range of parameters, such as duration of hospital stay and assessment of the neurological outcomes of the patients.

Comparison of Lanthanide Macrocyclic Complexes as 23Na NMR Sensors.

Nuclear magnetic resonance (NMR) agents, composed of paramagnetic lanthanide ions (Ln3+) complexed with negatively charged cyclic chelating agents (Che(n+3)-) forming polyanionic lanthanide complexes (LnChen-), perturb sodium-23 (23Na) signals, a phenomenon which depends sodium ions (Na+) exchanging with LnChen-. We analyzed 23Na shiftability and broadening due to hyperfine and bulk magnetic susceptibility (BMS) effects that arise from LnChen- designs using selective Ln3+ ions (i.e., thulium, Tm3+; gadolinium, Gd3+; and europium, Eu3+) and macrocyclics derived from 1,4,7,10-tetraazacyclododecane (cyclen) [i.e., with phosphonate (DOTP8-) and carboxylate (DOTMA4-) arms] and 1,4,7-triazacyclononane (TACN) [i.e., with phosphonate (NOTP6-) arms]. All LnChen- complexes showed downfield shifts, but Gd3+ and Tm3+ agents, respectively, were dominated by BMS and hyperfine effects, in good agreement with theory. While 23Na shiftability and broadening were minimally affected by pH and competing cations (K+, Ca2+, and Mg2+) within physiological ranges, the 23Na shiftability and broadening were most sensitive to LnChen- concentration in relation to the interstitial Na+ level in vivo. Greatest 23Na shiftability and broadening were obtained with Tm3+ and Gd3+ agents, respectively. While BMS contribution to shiftability was most impacted by the number of unpaired electrons on Ln3+, negative charge on LnChen- regulated Na+ exchange for line broadening. In brain tumor models, TmDOTP5- with 23Na-NMR has been used previously to separate Na+ in intracellular, blood, and interstitial pools, while evidence here shows that GdDOTP5- can distinguish Na+ within intracellular and extracellular (i.e., blood and interstitial) pools. Given the biological importance of Na+ in vivo, future macrocyclic designs of LnChen- should be sought for 23Na-NMR biomedical applications.

Understanding the interaction of proteins to ion exchange chromatographic supports: A surface energetics approach.

Ion exchange chromatography is one of the most widely used chromatographic technique for the separation and purification of important biological molecules. Due to its wide applicability in separation processes, a targeted approach is required to suggest the effective binding conditions during ion exchange chromatography. A surface energetics approach was used to study the interaction of proteins to different types of ion exchange chromatographic beads. The basic parameters used in this approach are derived from the contact angle, streaming potential, and zeta potential values. The interaction of few model proteins to different anionic and cationic exchanger, with different backbone chemistry, that is, agarose and methacrylate, was performed. Generally, under binding conditions, it was observed that proteins having negative surface charges showed strong to lose interaction (20 kT for Hannilase to 0.5 kT for IgG) with different anionic exchangers (having different positive surface charges). On the contrary, anionic exchangers showed almost no interaction (0-0.1 kT) with the positively charged proteins. An inverse behavior was observed for the interaction of proteins to cationic exchangers. The outcome from these theoretical calculations can predict the binding behavior of different proteins under real ion exchange chromatographic conditions. This will ultimately propose a better bioprocess design for protein separation.

Dysregulated proton and sodium gradients highlight cancer invasion and proliferation.

Acidity and salinity of the extracellular fluid, reflecting degrees of acid and sodium contents respectively, regulate essential cellular functions in health and disease, especially cancer. Tumor invasiveness is enhanced by the acidic extracellular milieu as a consequence of upregulated aerobic glycolysis. But recent discoveries also suggest that enhanced proliferative mitosis, which also hallmarks cancer, is impacted by interstitial salinity. Abnormal transmembrane proton/sodium gradients lead to pathophysiological alterations at the cellular level. These novel perspectives mandate pioneering imaging of extracellular acidity and salinity, preferably monitored simultaneously. By dissecting the interplay between dysregulated pH and electrolyte imbalance within the tumor habitat, these biomarkers hold promise for early cancer diagnosis and tracking therapies, from chemotherapy to immunotherapy.

High-resolution pH imaging using ratiometric chemical exchange saturation transfer combined with biosensor imaging of redundant deviation in shifts featuring paramagnetic DOTA-tetraglycinate agents.

Chemical exchange saturation transfer (CEST) and biosensor imaging of redundant deviation in shifts (BIRDS) methods differ respectively by detecting exchangeable and nonexchangeable proton signals by magnetic resonance. Because CEST contrast depends on both temperature and pH, simultaneous CEST and BIRDS imaging can be employed to separate these contributions. Here, we test if high-resolution pH imaging in vivo is possible with ratiometric CEST calibrated for temperature variations measured by BIRDS. Thulium- and europium-based DOTA-tetraglycinate agents, TmDOTA-(gly)4- and EuDOTA-(gly)4- , were used for high-resolution pH mapping in vitro and in vivo, using BIRDS for temperature adjustments needed for a more accurate ratiometric CEST approach. Although neither agent showed pH dependence with BIRDS in vitro in the pH range 6 to 8, each one's temperature sensitivity was enhanced when mixed because of increased redundancy. By contrast, the CEST signal of each agent was affected by the presence of the other agent in vitro. However, pH could be measured more accurately when temperature from BIRDS was detected. These in vitro calibrations with TmDOTA-(gly)4- and EuDOTA-(gly)4- enabled high-resolution pH imaging of glioblastoma in rat brains. It was concluded that temperature mapping with BIRDS can calibrate the ratiometric CEST signal from a cocktail of TmDOTA-(gly)4- and EuDOTA-(gly)4- agents to provide temperature-independent absolute pH imaging in vivo.

Imaging Hallmarks of the Tumor Microenvironment in Glioblastoma Progression.

Glioblastoma progression involves multifaceted changes in vascularity, cellularity, and metabolism. Capturing such complexities of the tumor niche, from the tumor core to the periphery, by magnetic resonance imaging (MRI) and spectroscopic imaging (MRSI) methods has translational impact. In human-derived glioblastoma models (U87, U251) we made simultaneous and longitudinal measurements of tumor perfusion (Fp), permeability (Ktrans), and volume fractions of extracellular (ve) and blood (vp) spaces from dynamic contrast enhanced (DCE) MRI, cellularity from apparent diffusion coefficient (ADC) MRI, and extracellular pH (pHe) from an MRSI method called Biosensor Imaging of Redundant Deviation in Shifts (BIRDS). Spatiotemporal patterns of these parameters during tumorigenesis were unique for each tumor. While U87 tumors grew faster, Fp, Ktrans, and vp increased with tumor growth in both tumors but these trends were more pronounced for U251 tumors. Perfused regions between tumor periphery and core with U87 tumors exhibited higher Fp, but Ktrans of U251 tumors remained lowest at the tumor margin, suggesting primitive vascularization. Tumor growth was uncorrelated with ve, ADC, and pHe. U87 tumors showed correlated regions of reduced ve and lower ADC (higher cellularity), suggesting ongoing proliferation. U251 tumors revealed that the tumor core had higher ve and elevated ADC (lower cellularity), suggesting necrosis development. The entire tumor was uniformly acidic (pHe 6.1-6.8) early and throughout progression, but U251 tumors were more acidic, suggesting lower aerobic glycolysis in U87 tumors. Characterizing these cancer hallmarks with DCE-MRI, ADC-MRI, and BIRDS-MRSI will be useful for exploring tumorigenesis as well as timely therapies targeted to specific vascular and metabolic aspects of the tumor microenvironment.

Imaging the transmembrane and transendothelial sodium gradients in gliomas.

Under normal conditions, high sodium (Na+) in extracellular (Na+e) and blood (Na+b) compartments and low Na+ in intracellular milieu (Na+i) produce strong transmembrane (ΔNa+mem) and weak transendothelial (ΔNa+end) gradients respectively, and these manifest the cell membrane potential (Vm) as well as blood-brain barrier (BBB) integrity. We developed a sodium (23Na) magnetic resonance spectroscopic imaging (MRSI) method using an intravenously-administered paramagnetic polyanionic agent to measure ΔNa+mem and ΔNa+end. In vitro 23Na-MRSI established that the 23Na signal is intensely shifted by the agent compared to other biological factors (e.g., pH and temperature). In vivo 23Na-MRSI showed Na+i remained unshifted and Na+b was more shifted than Na+e, and these together revealed weakened ΔNa+mem and enhanced ΔNa+end in rat gliomas (vs. normal tissue). Compared to normal tissue, RG2 and U87 tumors maintained weakened ΔNa+mem (i.e., depolarized Vm) implying an aggressive state for proliferation, whereas RG2 tumors displayed elevated ∆Na+end suggesting altered BBB integrity. We anticipate that 23Na-MRSI will allow biomedical explorations of perturbed Na+ homeostasis in vivo.