Notes

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nstructions for Authors for a complete description of levels of evidence.
Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
To evaluate whether different gamma-aminobutyric acidergic (GABAergic) sedatives such as propofol and benzodiazepines carry differential risks of post-extubation delirium in the ICU.

Retrospective cohort study.

Seven ICUs in an academic hospital network, Beth Israel Deaconess Medical Center (Boston, MA).

Ten thousand five hundred and one adult patients mechanically ventilated for over 24 hours.

None.

We tested the hypothesis that benzodiazepine versus propofol-based sedation is associated with fewer delirium-free days within 14 days after extubation. Further, we hypothesized that the measured sedation level evoked by GABAergic drugs is a better predictor of delirium than the drug dose administered. The proportion of GABAergic drug-induced deep sedation was defined as the ratio of days with a mean Richmond Agitation-Sedation Scale of less than or equal to -3 during mechanical ventilation. Multivariable regression and effect modification analyses were used. Delirium-free days were lower in patients mechanical ventilation with benzodiazepines compared with propofol is associated with increased risk of post-extubation delirium. Our data do not support the view that benzodiazepine-based compared with propofol-based sedation in the ICU is an independent risk factor of delirium, as long as deep sedation can be avoided in these patients.
To determine whether IV vitamin C therapy reduces 28-day mortality in patients with septic shock.

Multicenter, double-blinded, randomized controlled trial.

One academic medical ICU and four community ICUs.

Of 167 adult patients within 24 hours of vasopressor initiation for septic shock, 126 consented to participation, and 124 received study drug and were included in analysis.

IV vitamin C (10 mg/mL in normal saline) administered as a 1,000-mg bolus over 30 minutes followed by continuous infusion of 250 mg/hr for 96 hours or placebo of equal volumes of normal saline.

Of 124 subjects receiving study drug and included in analysis, 60 received vitamin C and 64 placebo. The primary outcome of all-cause 28-day mortality (vitamin C, 26.7%; placebo, 40.6%; p = 0.10) was lower in the vitamin C arm but did not reach statistical significance. Initiation of renal replacement therapy was higher in the vitamin C arm (vitamin C, 16.7%; placebo, 3.3%; p = 0.015), as was volume of fluid administration within 6 hours of study drug initiation (vitamin C, 1.07 L; placebo, 0.76 L; p = 0.03). There were no statistically significant differences in other secondary outcomes. In post hoc subgroup analysis, there was a decrease in 28-day mortality in the vitamin C arm among patients requiring positive-pressure ventilation at the time of enrollment (vitamin C, 36.3%; placebo, 60.0%; p = 0.05). This trial is registered at clinicaltrials.gov under identifier NCT03338569.

Vitamin C monotherapy failed to significantly reduce mortality in septic shock patients as hypothesized. Our findings do not support its routine clinical use for this purpose.
Vitamin C monotherapy failed to significantly reduce mortality in septic shock patients as hypothesized. Our findings do not support its routine clinical use for this purpose.
Concise definitive review of the reinitiation of prior-to-admission neuropsychiatric medications (NPMs) in ICU patients.

Available literature on PubMed and MEDLINE databases.

Available clinical trials and observational studies addressing the reinitiation of select NPMs (antidepressants, antipsychotics, and gabapentinoids) on various outcomes were included.

Eligible studies were identified by authors, and recommendations were summarized.

Agitation and delirium are recognized as common complications of patients in the ICU. While there is literature that suggests patients can acutely withdraw from opioids, less data are known about withdrawal from NPM such as antidepressants, antipsychotics, and gabapentinoids. However, there is some literature that suggests reinitiating some NPMs may lead to reductions in agitation, delirium, and hospital and ICU length of stay.

Additional larger studies are needed to evaluate the safety and efficacy of reinitiation of select prior-to-admission NPM to prevent agitation and delirium in ICU patients. BMS493 ic50 Multiple factors for NPM reinitiation should be considered, such as reason for admission, organ dysfunction, available route of administration to provide prior-to-admission NPM, concomitant additional medications for agitation and delirium, and safety of these medications for patients in the ICU.
Additional larger studies are needed to evaluate the safety and efficacy of reinitiation of select prior-to-admission NPM to prevent agitation and delirium in ICU patients. Multiple factors for NPM reinitiation should be considered, such as reason for admission, organ dysfunction, available route of administration to provide prior-to-admission NPM, concomitant additional medications for agitation and delirium, and safety of these medications for patients in the ICU.
The role of augmented internal anal sphincter (IAS) tone in the genesis of chronic anal fissure (CAF) is still unclear. Lateral internal sphincterotomy (LIS) is the most employed surgical procedure, aiming to reduce the IAS tone leaving a permanent anatomical alteration and it is burdened by high risk post-operative anal incontinence (AI). The aim of this work was to evaluate if the pre-operative manometric alterations of CAFs with hypertonic IAS would normalize after sphincter preserving surgical procedure.

We enrolled 108 consecutive patients affected by idiopathic and non-recurrent CAF undergone fissurectomy and anoplasty with V-Y cutaneous flap advancement and pharmacological sphincterotomy, matched with 54 healthy subject in a 1 to 2 ratio, and followed up for at least for 2 years. The goals were patient's complete healing, the evaluation of AI, recurrence rate and manometry parameters.

All wounds healed within 40 days after surgery. We recorded 7 cases of recurrences healed with medical therapy. We recorded 3 "de novo" post-operative cases of AI all temporary and low grade. Pre-operative values of maximum resting pressure (MRP) and detection of ultraslow wave activity (USWA) were significantly higher than in the healthy control group, but both come back to be similar to those recorded in healthy subject after 24 months from the surgery.

The high healing rate without post-operative "de novo" AI cases with the normalization of manometric parameters suggest that fissurectomy and anoplasty with V-Y cutaneous advancement flap and pharmacological sphincterotomy is an adequate procedure for the treatment of CAF with IAS hypertonia.

Anal fissure, Anoplasty, Fissurectomy, Proctology, Sphincterotomy.
Anal fissure, Anoplasty, Fissurectomy, Proctology, Sphincterotomy.Cholecystogastric fistulas is a rare complication of gallstone. Even if well described in the literature, this condition still poses a debate on diagnosis and surgical treatment. We present a case of a 35 year's old female which unexpectedly presented a cholecystogastric fistula during a laparoscopic cholecystectomy, treated successfully with fistula transection and repair and cholecystectomy through an open access. The open access remains the preferable option in this cases but laparoscopic techniques are being used worldwide with increasing success. The preoperative diagnosis remains difficult for the unspecific symptoms. KEY WORDS Biliodigestive Fistula, Gallstone Ileus, Gastric Fistula, Biliary Fistula, Cholecystitis.
We aim to show that fistula ablation with laser (FAL) is a reliable method to repair a perianal fistula, and we share the results of a 24-month follow-up on FAL treatments of different perianal fistula types.

The FAL procedure was performed using a ceramic diode laser platform (30-50 J/cm of energy at a wavelength of 1470 nm). All operations were performed under spinal anesthesia in the jackknife position.

Of the 67 patients, 48 (71.6%) were male and 19 (28.4%) were female. Of these, 40 (59.7%) had intersphincteric fistulas, 21 (31.3%) had transsphincteric fistulas, 3 (4.47%) had suprasphincteric fistulas, and 3 (4.47%) had extrasphincteric fistulas. Based on perianal fistula disease severity scores, 40 patients (59.70%) experienced complete healing, 10 (14.92%) had persistent symptomatic drainage, 14 (20.89%) had slight drainage with minimal symptoms, and 3 (4.47%) had painful, symptomatic drainage. No major complications were observed in any patient.

The FAL is a minimally invasive initiative with the lowest morbidity and highest curative recovery rate, especially for simple fistulas.

Anal fistula, Fistula ablation with laser, Reliable surgery.
Anal fistula, Fistula ablation with laser, Reliable surgery.Osteopontin (OPN) has been proved to be closely related to the pathogenesis of osteoarthritis (OA), but the role of OPN in the pathogenesis of OA has not been fully clarified. Current studies on OPN in OA mostly focus on articular cartilage, synovial membrane and articular fluid, while ignoring its role in OA subchondral bone turnover and remodeling. In this study, we used a destabilization OA mouse model to investigate the role of OPN in OA subchondral bone changes. Our results indicate that increased expression of OPN accelerates the turnover and remodeling of OA subchondral bone, promotes the formation of h-type vessels in subchondral bone, and mediates articular cartilage degeneration induced by subchondral bone metabolism. In addition, our results confirmed that inhibition of PI3K/AKT signaling pathway inhibits OPN-mediated OA subchondral bone remodeling and cartilage degeneration. This study revealed the role and mechanism of OPN in OA subchondral bone, which is of great significance for exploring specific biological indicators for early diagnosis of OA and monitoring disease progression, as well as for developing drugs to regulate the metabolism and turnover of subchondral bone and alleviate the subchondral bone sclerosis of OA.An 89-year-old woman was referred to our cath lab for a primary percutaneous coronary intervention following electrocardiographic evidence of inferior ST-segment elevation myocardial infarction. A coronary angiography revealed single- vessel disease with complete occlusion of the right coronary artery. After crossing the occlusion with a guidewire, we proceeded with manual thrombectomy using the Eliminate Aspiration Catheter (Terumo Europe). To our knowledge, this is the longest coronary thrombus ever reported to be removed in its entirety.Although the collagen-based Manta closure device (Teleflex) is a safe and effective option to close large-bore arterial access sites, complications can occur in at-risk cohorts, as seen in this clinical scenario. It is important for clinicians to share these complications as new technology is introduced.Stent fracture is a rather infrequent complication associated with in-stent restenosis, thrombosis, aneurysm formation, and ischemic events. Several stent-related parameters, such as the use of longer or multiple stents, stent overlapping, and balloon/stent overexpansion are potential predictors of stent fracture. Stents deployed in right coronary artery lesions with exaggerated motion, tortuosity, or severe calcification are also generally considered to be at higher risk for fracture. This case demonstrates that intravascular ultrasound imaging is extremely useful to confirm the diagnosis and identify the possible mechanism of the stent fracture, as well as to assess the final result after subsequent angioplasty.
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