Effect of low vs. high vancomycin trough level on the clinical outcomes of adult patients with sepsis or gram-positive bacterial infections: a systematic review and meta-analysis.

BACKGROUND & OBJECTIVE: The Infectious Disease Society of America guidelines recommend vancomycin trough levels of 15-20 mg/L for severe methicillin-resistant Staphylococcus aureus. However, recent consensus guidelines of four infectious disease organizations no longer recommend vancomycin dosing using minimum serum trough concentrations. Therefore, this study aimed to evaluate the impact of low (< 15 mg/L) vs. high (≥ 15 mg/L) vancomycin trough levels on clinical outcomes in adult patients with sepsis or gram-positive bacterial infections. METHOD: A systematic literature review from inception to December 2022 was conducted using four online databases, followed by a meta-analysis. The outcomes of interest included clinical response/efficacy, microbial clearance, length of ICU stay, treatment failure, nephrotoxicity, and mortality. RESULTS: Fourteen cohort studies met the inclusion criteria from which vancomycin trough concentration data were available for 5,228 participants. Our analysis found no association between vancomycin trough levels and clinical response [OR = 1.06 (95%CI 0.41-2.72], p = 0.91], microbial clearance [OR = 0.47 (95% CI 0.23-0.96), p = 0.04], ICU length of stay [MD=-1.01 (95%CI -5.73-3.71), p = 0.68], or nephrotoxicity [OR = 0.57 (95% CI 0.31-1.06), p = 0.07]. However, low trough levels were associated with a non-significant trend towards a lower risk of treatment failure [OR = 0.89 (95% CI 0.73-1.10), p = 0.28] and were significantly associated with reduced risk of all-cause mortality [OR = 0.74 (95% CI 0.62-0.90), p = 0.002]. CONCLUSION: Except for a lower risk of treatment failure and all-cause mortality at low vancomycin trough levels, this meta-analysis found no significant association between vancomycin trough levels and clinical outcomes in adult patients with sepsis or gram-positive bacterial infections.

Antiarrhythmic drug therapy and catheter ablation in patients with paroxysmal or persistent atrial fibrillation: a systematic review and meta-analysis.

BACKGROUND: Catheter ablation and antiarrhythmic drug therapy are utilized for rhythm control in atrial fibrillation (AF), but their comparative effectiveness, especially with contemporary treatment modalities, remains undefined. We conducted a systematic review and meta-analysis contrasting current ablation techniques against antiarrhythmic medications for AF. METHODS: We searched PubMed, SCOPUS, Cochrane CENTRAL, and Web of Science until November 2023 for randomized trials comparing AF catheter ablation with antiarrhythmics, against antiarrhythmic drug therapy alone, reporting outcomes for > 6 months. Four investigators extracted data and appraised risk of bias (ROB) with ROB 2 tool. Meta-analyses estimated pooled efficacy and safety outcomes using R software. RESULTS: Twelve trials (n = 3977) met the inclusion criteria. Catheter ablation was associated with lower AF recurrence (relative risk (RR) = 0.44, 95%CI (0.33, 0.59), P ˂ 0.0001) and hospitalizations (RR = 0.44, 95%CI (0.23, 0.82), P = 0.009) than antiarrhythmic medications. Catheter ablation also improved the physical quality of life component score (assessed by a 36-item Short Form survey) by 7.61 points (95%CI -0.70-15.92, P = 0.07); but, due to high heterogeneity, it was not statistically significant. Ablation was significantly associated with higher procedural-related complications [RR = 15.70, 95%CI (4.53, 54.38), P < 0.0001] and cardiac tamponade [RR = 9.22, 95%CI (2.16, 39.40), P = 0.0027]. All-cause mortality was similar between the two groups. CONCLUSIONS: For symptomatic AF, upfront catheter ablation reduces arrhythmia and hospitalizations better than continued medical therapy alone, albeit with moderately more adverse events. Careful patient selection and risk-benefit assessment are warranted regarding the timing of ablation.

Mortality, morbidity & clinical outcome with different types of vasopressors in out of hospital cardiac arrest patients- a systematic review and meta-analysis.

BACKGROUND & OBJECTIVE: Despite their continued use, the effectiveness and safety of vasopressors in post-cardiac arrest patients remain controversial. This study examined the efficacy of various vasopressors in cardiac arrest patients in terms of clinical, morbidity, and mortality outcomes. METHODS: A comprehensive literature search was performed using online databases (MeSH terms: MEDLINE (Ovid), CENTRAL (Cochrane Library), Embase (Ovid), CINAHL, Scopus, and Google Scholar) from 1997 to 2023 for relevant English language studies. The primary outcomes of interest for this study included short-term survival leading to death, return of spontaneous circulation (ROSC), survival to hospital discharge, neurological outcomes, survival to hospital admission, myocardial infarction, and incidence of arrhythmias. RESULTS: In this meta-analysis, 26 studies, including 16 RCTs and ten non-RCTs, were evaluated. The focus was on the efficacy of epinephrine, vasopressin, methylprednisolone, dopamine, and their combinations in medical emergencies. Epinephrine treatment was associated with better odds of survival to hospital discharge (OR = 1.52, 95%CI [1.20, 1.94]; p < 0.001) and achieving ROSC (OR = 3.60, 95% CI [3.45, 3.76], P < 0.00001)) over placebo but not in other outcomes of interest such as short-term survival/ death at 28-30 days, survival to hospital admission, or neurological function. In addition, our analysis indicates non-superiority of vasopressin or epinephrine vasopressin-plus-epinephrine therapy over epinephrine monotherapy except for survival to hospital admission where the combinatorial therapy was associated with better outcome (0.76, 95%CI [0.64, 0.92]; p = 0.004). Similarly, we noted the non-superiority of vasopressin-plus-methylprednisolone versus placebo. Finally, while higher odds of survival to hospital discharge (OR = 3.35, 95%CI [1.81, 6.2]; p < 0.001) and ROSC (OR = 2.87, 95%CI [1.97, 4.19]; p < 0.001) favoring placebo over VSE therapy were observed, the risk of lethal arrhythmia was not statistically significant. There was insufficient literature to assess the effects of dopamine versus other treatment modalities meta-analytically. CONCLUSION: This meta-analysis indicated that only epinephrine yielded superior outcomes among vasopressors than placebo, albeit limited to survival to hospital discharge and ROSC. Additionally, we demonstrate the non-superiority of vasopressin over epinephrine, although vasopressin could not be compared to placebo due to the paucity of data. The addition of vasopressin to epinephrine treatment only improved survival to hospital admission.

Evaluating the efficacy of different volume resuscitation strategies in acute pancreatitis patients: a systematic review and meta-analysis.

INTRODUCTION: Acute pancreatitis poses a significant health risk due to the potential for pancreatic necrosis and multi-organ failure. Fluid resuscitation has demonstrated positive effects; however, consensus on the ideal intravenous fluid type and infusion rate for optimal patient outcomes remains elusive. METHODS: A comprehensive literature search was conducted using PubMed, Embase, the Cochrane Library, Scopus, and Google Scholar for studies published between 2005 and January 2023. Reference lists of potential studies were manually searched to identify additional relevant articles. Randomized controlled trials and retrospective studies comparing high (≥ 20 ml/kg/h), moderate (≥ 10 to < 20 ml/kg/h), and low (5 to < 10 ml/kg/h) fluid therapy in acute pancreatitis were considered. RESULTS: Twelve studies met our inclusion criteria. Results indicated improved clinical outcomes with low versus moderate fluid therapy (OR = 0.73; 95% CI [0.13, 4.03]; p = 0.71) but higher mortality rates with low compared to moderate (OR = 0.80; 95% CI [0.37, 1.70]; p = 0.55), moderate compared to high (OR = 0.58; 95% CI [0.41, 0.81], p = 0.001), and low compared to high fluids (OR = 0.42; 95% CI [0.16, 1.10]; P = 0.08). Systematic complications improved with moderate versus low fluid therapy (OR = 1.22; 95% CI [0.84, 1.78]; p = 0.29), but no difference was found between moderate and high fluid therapy (OR = 0.59; 95% CI [0.41, 0.86]; p = 0.006). DISCUSSION: This meta-analysis revealed differences in the clinical outcomes of patients with AP receiving low, moderate, and high fluid resuscitation. Low fluid infusion demonstrated better clinical outcomes but higher mortality, systemic complications, and SIRS persistence than moderate or high fluid therapy. Early fluid administration yielded better results than rapid fluid resuscitation.

Mortality and mode of dialysis: meta-analysis and systematic review.

BACKGROUND: The global use of kidney replacement therapy (KRT) has increased, mirroring the incidence of acute kidney injury and chronic kidney disease. Despite its growing clinical usage, patient outcomes with KRT modalities remain controversial. In this meta-analysis, we sought to compare the mortality outcomes of patients with any kidney disease requiring peritoneal dialysis (PD), hemodialysis (HD), or continuous renal replacement therapy (CRRT). METHODS: The investigation was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). PubMed (MEDLINE), Cochrane Library, and Embase databases were screened for randomized trials and observational studies comparing mortality rates with different KRT modalities in patients with acute or chronic kidney failure. A random-effects model was applied to compute the risk ratio (RR) and 95% confidence intervals (95%CI) with CRRT vs. HD, CRRT vs. PD, and HD vs. PD. Heterogeneity was assessed using I2 statistics, and sensitivity using leave-one-out analysis. RESULTS: Fifteen eligible studies were identified, allowing comparisons of mortality risk with different dialytic modalities. The relative risk was non-significant in CRRT vs. PD [RR = 0.95, (95%CI 0.53, 1.73), p = 0.92 from 4 studies] and HD vs. CRRT [RR = 1.10, (95%CI 0.95, 1.27), p = 0.21 from five studies] comparisons. The findings remained unchanged in the leave-one-out sensitivity analysis. Although PD was associated with lower mortality risk than HD [RR = 0.78, (95%CI 0.62, 0.97), p = 0.03], the significance was lost with the exclusion of 4 out of 5 included studies. CONCLUSION: The current evidence indicates that while patients receiving CRRT may have similar mortality risks compared to those receiving HD or PD, PD may be associated with lower mortality risk compared to HD. However, high heterogeneity among the included studies limits the generalizability of our findings. High-quality studies comparing mortality outcomes with different dialytic modalities in CKD are necessary for a more robust safety and efficacy evaluation.

Intrathecal iodinated contrast-induced transient spinal shock.

Transient spinal shock is a previously unreported complication of intrathecal contrast. A 63-year-old man presented with the chief complaint of worsening back pain. Computed topography of lumbar spine without contrast showed a lytic lesion. After international normalized ratio (INR) correction, patient was sent for CT myelogram. After intrathecal contrast injection, the patient dropped his blood pressure profoundly and developed clinical manifestations of spinal shock. Emergent intravenous bolus fluids were initiated resulting in improvement in blood pressure. Patient's spinal shock resolved within hours. CT myelogram was normal except previously known lytic lesion. It was concluded that the transient shock was most likely due to contrast injection. We believe that this is the first reported case of transient spinal shock following CT myelogram using water-soluble iodinated non-ionic contrast agent administered intrathecally.

Why is That Chin Numb? A Case of Burkitt's Lymphoma Presenting as Numb Chin Syndrome.

We report a case of numb chin syndrome (NCS) that preceded the diagnosis of Burkitt's lymphoma (BL) and discuss our findings with emphasis on metastatic malignancies in general and BL in particular causing NCS. A 73-year-old woman presented with worsening right-sided back pain for a week along with right-sided leg weakness and a progressive thigh and perianal numbness. She reported numbness of the chin which started two weeks prior. MRI showed compression of the cauda equina which was highly suggestive of neoplastic process. After debulking mass surgery, biopsy of the tissue from spine revealed BL. The patient received a round of radiotherapy of spine and multiple rounds of chemotherapy. Six months later she had reoccurrence of lymphoma with metastasis and eventually passed away. Presence of NCS in the setting of an underlying malignancy indicates very poor prognosis. In appropriate clinical setting, NCS should trigger work up for an underlying malignancy.

Metformin-associated Lactic Acidosis Successfully Treated with Continuous Renal Replacement Therapy.

Metformin-associated lactic acidosis (MALA) is a potentially lethal condition that can result from the use of metformin in the setting of the risk factors such as renal insufficiency or hypoperfusion. We present a case of metformin-associated lactic acidosis incited by pyelonephritis-induced septic shock where use of continuous renal replacement therapy (CRRT) led to good recovery. A 51-year-old female with confusion and abdominal pain was brought to the emergency department (ED). She had a significant past medical history of type ll diabetes mellitus and recurrent urinary tract infections. Prior to the arrival to the hospital, she was conscious but confused and noted to have a low blood glucose level, which was managed with glucose per orally by emergency medical services. While in ED patient was dehydrated and hemodynamically unstable. She failed to respond to intravenous fluids hence vasopressors along with ceftriaxone were initiated. Intubation for mechanical ventilation was performed for respiratory failure and evolving septic shock, sodium bicarbonate for severe metabolic acidosis was started and antibiotics were stepped up to vancomycin and cefepime. The patient was transferred to the medical intensive care unit. Her kidney function continued to worsen, and she remained profoundly acidotic despite aggressive measures. A diagnosis of concomitant MALA was made since vasopressor requirement was less than expected considering the severity of acidosis. Emergent CRRT was initiated, resulting in improvement of acidosis in 24 hours. After she was stabilized vasopressors were stopped, she was extubated, and antibiotics were de-escalated to the oral regimen. MALA is rare but life-threatening complication of metformin use, especially in critically ill patients. CRRT should be considered as the first line in the treatment of metformin-related lactic acidosis, especially in the setting of hemodynamic instability.