anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Objective: To observe the clinical efficacy of a new type of "firebreak" drainage with skin preservation in the treatment of Fournier's gangrene. Methods: This technique is suitable for patients with perianal necrotizing fasciitis who can tolerate surgery without large area of skin blackness and necrosis. Procedure and key points: (1) The dividing line between inflammatory tissue and normal tissue was determined according to imaging examination and intraoperative exploration; (2) The abscess cavity was cut along the most obvious part of the abscess fluctuation, with a long diameter of 3~4 cm and a short diameter of 1~2 cm; (3) Necrotic tissue was discreetly separated and removed from the main incision to the outer edge of the infection. A fusiform incision was made every 3 to 5 cm, with a long diameter of 2 to 3 cm and a short diameter of 1 cm, and discreetly separated until the normal tissue, and a hose was hung between the adjacent incisions for drainage. (4) Each adjacent edge cut between the stealth separation and hanging hose drainage, forming a "firebreak"; (5) Rinse the wound repeatedly; (6) If the infection invades the rectum, colostomy is performed as required. The case data of 11 patients with perianal necrotizing fasciitis admitted to the Second Affiliated Hospital of Nanjing University of Chinese Medicine from July 2019 to February 2023 were retrospectively analyzed. All patients were treated with emergency surgical debridement by "firebreak" drainage with skin preservation. Results: All 11 cases were cured with 100%. One case underwent multiple operations. The hospitalization time was 11-46 days, with an average of 22 days. The wound healing time was 28-75 days, with an average of 43 days. Except for 1 patient with trauma, all the other patients had no significant anal function injury after surgery. All the 11 patients recovered and were discharged from hospital with a median follow-up of 136 (115-413) days. Conclusions: The "firebreak" drainage based on skin preservation has the advantages of less trauma and faster recovery, and do not cause obvious anal function damage.
OBJECTIVE: Sepsis-induced cardiomyopathy (SICM) is a life-threatening complication. Phospholipase D2 (PLD2) is crucial in mediating inflammatory reactions and is associated with the prognosis of patients with sepsis. Whether PLD2 is involved in the pathophysiology of SICM remains unknown. This study aimed to investigate the effect of PLD2 knockout on SICM and to explore potential mechanisms.
METHODS: The SICM model was established using cecal ligation and puncture in wild-type and PLD2-knockout mice and lipopolysaccharide (LPS)-induced H9C2 cardiomyocytes. Transfection with PLD2-shRNA lentivirus and a PLD2 overexpression plasmid were used to interfere with PLD2 expression in H9C2 cells. Cardiac pathological alterations, cardiac function, markers of myocardial injury, and inflammatory factors were used to evaluate the SICM model. The expression of pyroptosis-related proteins (NLRP3, cleaved caspase 1, and GSDMD-N) was assessed using western blotting, immunofluorescence, and immunohistochemistry.
RESULTS: SICM mice had myocardial tissue damage, increased inflammatory response, and impaired heart function, accompanied by elevated PLD2 expression. PLD2 deletion improved cardiac histological changes, mitigated cTNI production, and enhanced the survival of the SICM mice. Compared with controls, PLD2-knockdown H9C2 exhibits a decrease in inflammatory markers and lactate dehydrogenase production, and scanning electron microscopy results suggest that pyroptosis may be involved. The overexpression of PLD2 increased the expression of NLRP3 in cardiomyocytes. In addition, PLD2 deletion decreased the expression of pyroptosis-related proteins in SICM mice and LPS-induced H9C2 cells.
CONCLUSION: PLD2 deletion is involved in SICM pathogenesis and is associated with the inhibition of the myocardial inflammatory response and pyroptosis through the NLRP3/caspase 1/GSDMD pathway.
Our previous study has identified that glutamate in the red nucleus (RN) facilitates the development of neuropathic pain through metabotropic glutamate receptors (mGluR). Here, we further explored the actions and possible molecular mechanisms of red nucleus mGluR Ⅰ (mGluR1 and mGluR5) in the development of neuropathic pain induced by spared nerve injury (SNI). Our data indicated that both mGluR1 and mGluR5 were constitutively expressed in the RN of normal rats. Two weeks after SNI, the expressions of mGluR1 and mGluR5 were significantly boosted in the RN contralateral to the nerve injury. Administration of mGluR1 antagonist LY367385 or mGluR5 antagonist MTEP to the RN contralateral to the nerve injury at 2 weeks post-SNI significantly ameliorated SNI-induced neuropathic pain. However, unilateral administration of mGluRⅠ agonist DHPG to the RN of normal rats provoked a significant mechanical allodynia, this effect could be blocked by LY367385 or MTEP. Further studies indicated that the expressions of TNF-α and IL-1β in the RN were also elevated at 2 weeks post-SNI. Administration of mGluR1 antagonist LY367385 or mGluR5 antagonist MTEP to the RN at 2 weeks post-SNI significantly inhibited the elevations of TNF-α and IL-1β. However, administration of mGluR Ⅰ agonist DHPG to the RN of normal rats significantly enhanced the expressions of TNF-α and IL-1β, these effects were blocked by LY367385 or MTEP. These results suggest that activation of red nucleus mGluR1 and mGluR5 facilitate the development of neuropathic pain by stimulating the expressions of TNF-α and IL-1β. mGluR Ⅰ maybe potential targets for drug development and clinical treatment of neuropathic pain.
Pindolol is rapidly and reproducibly absorbed (greater than 95%), achieving peak plasma concentrations within 1 hour of drug administration. Pindolol has no significant first-pass effect. The blood concentrations are proportional in a linear manner to the administered dose in the range of 5 mg to 20 mg. Upon repeated administration to the same subject, variation is minimal. After a single dose, intersubject variation for peak plasma concentrations was about 4-fold (e.g., 45 to 167 ng/mL for a 20 mg dose). Upon multiple dosing, intersubject variation decreased to 2- to 2.5-fold. Pindolol is only 40% bound to plasma proteins and is evenly distributed between plasma and red cells. The volume of distribution in healthy subjects is about 2 L/kg.  
Pindolol undergoes extensive metabolism in animals and man. In man, 35% to 40% is excreted unchanged in the urine and 60% to 65% is metabolized primarily to hydroxy-metabolites which are excreted as glucuronides and ethereal sulfates. The polar metabolites are excreted with a half-life of approximately 8 hours and thus multiple dosing therapy (q.8H) results in a less than 50% accumulation in plasma. About 6% to 9% of an administered intravenous dose is excreted by the bile into the feces.

The disposition of pindolol after oral administration is monophasic with a half-life in healthy subjects or hypertensive patients with normal renal function of approximately 3 to 4 hours. Following t.i.d. administration (q.8H), no significant accumulation of pindolol is observed.

In elderly hypertensive patients with normal renal function, the half-life of pindolol is more variable, averaging about 7 hours, but with values as high as 15 hours.

In hypertensive patients with renal diseases, the half-life is within the range expected for healthy subjects. However, a significant decrease (50%) in volume of distribution (VD) is observed in uremic patients and VD appears to be directly correlated to creatinine clearance. Therefore, renal drug clearance is significantly reduced in uremic patients, resulting in a significant decrease in urinary excretion of unchanged drug. Uremic patients with a creatinine clearance of less than 20 mL/min generally excreted less than 15% of the administered dose unchanged in the urine.

In patients with histologically diagnosed cirrhosis of the liver, the elimination of pindolol was more variable in rate and generally significantly slower than in healthy subjects. The total body clearance of pindolol in cirrhotic patients ranged from about 50 to 300 mL/min and was directly correlated to antipyrine clearance. The half-life ranges from 2.5 hours to greater than 30 hours. These findings strongly suggest that caution should be exercised in dosage adjustments of pindolol in such patients.

The bioavailability of pindolol is not significantly affected by coadministration of food, hydralazine, hydrochlorothiazide or aspirin. Pindolol has no effect on warfarin activity or the clinical effectiveness of digoxin, although small transient decreases in plasma digoxin concentrations were noted.
The standard treatment of oral cavity, oropharynx, hypopharynx, and cavum cancers is external radiotherapy. However, one of the associated toxicities is the occurrence of mucositis which can be a limiting factor in the treatment (dose reduction or treatment interruption can limit patient's survival), patient's quality of life decreases and severe complications can occur. The treatment of mucositis is mainly symptomatic; a randomized study has shown a benefit of a mouthwash with Benzydamine, a non steroidal anti-inflammatory drug, for patients receiving 50-Gy radiation. Another study with a lower number of patients has also shown a benefit of using a zinc sulfate solution. Boiron laboratories have developed a phytopharmaceutical preparation, Homeodent®, which has no secondary effects and which could prevent radiation-induced mucositis. This study will evaluate the efficiency of mouthwash with Homeodent® in a large randomized trial.
OBJECTIVE: To report a novel anatomical pattern of autoimmune encephalitis characterized by strictly unilateral cortical inflammation and a clinical picture overlapping with late-onset Rasmussen's encephalitis.
METHODS: We retrospectively gathered data of patients identified at two tertiary referral academic centers who met inclusion criteria.
RESULTS: We identified twelve cases (average age 65, +/- 19.8 years, 58% female). All patients had unilateral cortical inflammation manifesting with focal seizures, cognitive decline, hemicortical deficits, and unilateral MRI and/or EEG changes. Six cases were idiopathic, two paraneoplastic, two iatrogenic (in the setting of immune checkpoint inhibitors), and two post-COVID-19. Serologically, ten patients were seronegative, one had high titer anti-GAD65, and one had anti-NMDAR. Five patients met Rasmussen's encephalitis criteria, and six did not fully meet the criteria but had symptoms significantly overlapping with the condition. Most patients had significant improvement with immunotherapy.
DISCUSSION: Unilateral cortical AE seems to be more prevalent in the elderly and more frequently idiopathic and seronegative. Patients with this anatomical variant of autoimmune encephalitis have overlapping features with late-onset Rasmussen's encephalitis but are more responsive to immunotherapy. In cases refractory to immunotherapy, interventions used in refractory Rasmussen's encephalitis may be considered, such as functional hemispherectomy.
Subjects will receive an initial injection of 1.0cc of Placental Matrix-Derived Mesenchymal Stem Cells (PMD-MSCs). Subjects will be eligible for re-injection at 3 months and/or 6 months as determined by the clinician based patient reported treatment satisfaction.
ETHNOPHARMACOLOGICAL RELEVANCE: Sida cordifolia L., a perennial subshrub belonging to the Malvaceae family, holds noteworthy significance in the Indian Ayurvedic System and global texts. Roots of this plant are reported to be useful in neurodegenerative disorders, facial paralysis, and treating several neuropathic pain conditions such as neuralgia, and sciatica. However, despite these claims, there remains a dearth of experimental evidence showcasing the effectiveness of Sida cordifolia L. roots in mitigating neuropathic pain.
AIM OF THE STUDY: The primary objective of this study was to assess the analgesic properties of the whole extract (SCE) obtained from the roots of Sida cordifolia L., as well as its aqueous fraction (SAF) in rat model of chronic constriction injury (CCI)-induced neuropathic pain. Furthermore, in-depth phytochemical and molecular biology studies were conducted to identify the potential phytoconstituents and unveil the underlying mechanisms of action.
MATERIAL AND METHODS: DCM: Methanol (1:1) was used to extract the roots of Sida cordifolia L. to get whole extract (SCE) and was subjected to phytochemical investigations including LC-MS analysis. Analgesic potential of SCE was evaluated in chronic constriction injury (CCI) model of neuropathic pain in rats followed by its bioactivity guided fractionation using in-vitro anti-inflammatory assay and assessment of most potent fraction (SAF) in in-vivo pain model. We have also performed the detailed phytochemical and molecular biology investigations to delineate the mechanism of action of Sida cordifolia root extract.
RESULTS: Chronic constriction injury leads to significant decrease in paw withdrawal threshold and paw withdrawal latency indicating development of hypersensitivity in rodents. Treatment with SCE and its most potent aqueous fraction (SAF) leads to significant and dose-dependent reduction in pain-like behavior of nerve injured rats. Pro-inflammatory cytokines (TNF-α, IL-1β), glia cell markers (Iba1, ICAM1), neuropeptides (CGRP and Substance P), KIF-17 and NR2B expressions were found to be significantly upregulated in DRG and spinal cord of nerve injured rats. Treatment with SCE and SAF suppressed oxido-inflammatory cascade along with attenuation of KIF-17 mediated NR2B trafficking and neuroinflammation in DRG and spinal tissues of neuropathic rats. HPTLC and HR-MS analysis suggest betaine as major constituent in SAF which along with other phytoconstituents.
CONCLUSIONS: Both the whole extract (SCE) and the aqueous fraction (SAF) demonstrate a significant reduction in mechanical and thermal hypersensitivity by inhibiting KIF-17 mediated NR2B signaling in nerve injured rats and may be used as a potential alternative for the treatment of chronic pain. Our findings support the use of roots of Sida cordifolia L. in neuropathic pain conditions as acclaimed by its traditional use.
In 2-year carcinogenicity studies, increases in the incidence of liver, kidney, and vascular tumors in female mice and a trend toward an increase in the incidence of liver tumors in male mice were observed at 450 mg/kg/day (providing approximately 5 times [females] or 8 times [males] the systemic exposure [AUC=64 mcg·hr/mL] achieved at the MRHD). No increase in the incidence of tumors was observed at 150 mg/kg/day (providing approximately 2 to 3 times the systemic exposure [AUC] achieved at the MRHD). In rats, an increase in the incidence of kidney tumors was observed in both sexes at 170 mg/kg/day (providing approximately 8 times [males] or 16 times [females] the systemic exposure [AUC] achieved at the MRHD). No increased incidence of kidney tumors was seen at 80 mg/kg/day (providing approximately 4 times [males] or 7 times [females] the systemic exposure [AUC] achieved at the MRHD). Although a dose-related increased incidence of benign Leydig cell tumors was observed, Leydig cell tumorigenesis was prevented by supplementing male rats with testosterone.   
Zileuton was negative in genotoxicity studies including bacterial reverse mutation (Ames) using S. typhimurium and E. coli, chromosome aberration in human lymphocytes,  in vitro unscheduled DNA synthesis (UDS), in rat hepatocytes with or without zileuton pretreatment and in mouse and rat kidney cells with zileuton pretreatment, and mouse micronucleus assays. However, a dose-related increase in DNA adduct formation was reported in kidneys and livers of female mice treated with zileuton. Although some evidence of DNA damage was observed in a UDS assay in hepatocytes isolated from Aroclor-1254-treated rats, no such finding was noticed in hepatocytes isolated from monkeys, where the metabolic profile of zileuton is more similar to that of humans.   
In reproductive performance/fertility studies, zileuton produced no effects on fertility in rats at oral doses up to 300 mg/kg/day (providing at least 10 times [male rats] and greater than 20 times [female rats] the systemic exposure [AUC] achieved at the MRHD). However, reduction in fetal implants was observed at oral doses of 150 mg/kg/day and higher (providing approximately 20 times the systemic exposure [AUC] achieved at the MRHD). Comparative systemic exposure (AUC) is based on measurements in male rats or nonpregnant female rats obtained from the comparable doses of 3-month or 1-year general toxicity study at similar dosages. Increases in gestation length, prolongation of estrus cycle, and increases in stillbirths were observed at oral doses of 75 mg/kg/day and higher (providing approximately 7 times the systemic exposure [AUC] achieved at the MRHD on an AUC basis with data obtained from the comparable doses of 2-year dietary carcinogenicity study). No adverse effects were observed at 15 mg/kg/day in the study at estimated exposure similar to that at the MRHD.
Introduction: The available evidence regarding the treatment of acute diverticulitis (AD) with pelvic abscess using antibiotics alone is very limited. The objective of this study was to determine whether the short- and long-term outcomes of AD with pelvic abscesses treated exclusively with antibiotics are comparable to those of pericolic abscesses. Methods: A retrospective study was conducted on patients diagnosed with AD and either pelvic or pericolic abscesses, as confirmed by computed tomography, who were treated solely with antibiotic therapy between 2011 and 2021. Cases involving percutaneous drainage as part of conservative treatment were excluded. Results: Fifty-eight patients met the inclusion criteria, comprising 12 with pelvic abscesses and 46 with pericolic abscesses. Both groups exhibited similar baseline characteristics and radiological findings, except for a more frequent presence of free fluid in pelvic abscesses. The success rate of antibiotic therapy was 91.7% for pelvic abscess cases and 96.7% for pericolic cases (p = 0.508). No significant differences were observed in recurrence or elective surgery. In the subgroup of abscesses with a diameter ≥4 cm, the evolution was similar in both locations (treatment success rate of 87.5% in pelvic and 94.4% in pericolic; p = 0.529), although recurrence was slightly higher for pericolic abscesses (38.4% vs. 14.3%; p = 0.362). Conclusions: Antibiotic therapy alone proves to be effective and safe for pelvic abscesses, demonstrating a course similar to pericolic abscesses, even in the case of large abscesses. Although the analyzed patient cohort is small, this study provides additional evidence that percutaneous drainage is not always essential for treating this complication.
AIM: Familial Mediterranean fever (FMF) is the most common inherited autoinflammatory disease in the world. There are known triggers to initiate an FMF attack, yet potential effects of intrauterine devices (IUD) in women of reproductive age have not been evaluated before.
METHOD: Consecutive female patients with FMF who ever used IUD over the age of 18 were enrolled. Female patients with FMF were sub grouped according to the type of IUD they use. FMF attack frequency, severity, duration, presence of dysmenorrhea, severity of dysmenorrhea, having attacks during menstruation before and after IUD use were questioned. Demographic and clinical data were collected from hospital database.
RESULTS: When all patients with IUD use were evaluated, it was found that the frequency of attacks increased after IUD insertion at 3rd and 12th months (median [min-max] attack frequency at 3rd month, 1 (0-3) vs 1 (0-6), p = 0.002, median [min-max] attack frequency at 12th month, 2 (0-12) vs 3.5 (0-18), p = 0.028). Attack severity measured by VAS pain was also significantly increased. Attack duration and menstrual pain was similar before and after IUD use. Attack frequency at 3rd and 12th months, attack severity and menstrual pain was all increased significantly in Cu-IUD users, whereas none of these parameters deteriorated in LNG-IUD group.
CONCLUSION: IUD use, especially Cu-IUD, may increase the frequency and severity of attacks in female patients with FMF. Clinicians may benefit from considering LGN-IUD if IUDs are preferred as contraception in women of childbearing age with FMF.
Fibers (3) at perforation (4) edges are bonded together. The edge bonding is by melting (5) or adhesion. Melt zones extend into edge regions of the fibers. The melt zones include the core regions of the fibers. The bonding includes elevations (7) projecting above the main surface (8) of the flat material, which are preferably 0.04-0.3 mm high. The bonding extends into a bonding region (6) around the perforations. The extent is preferably 150-350 times the fiber diameter of the fleece material (2). It is annular, especially elliptical. The fibers include continuous filaments. At least some have a titer less than 1 dtex. The weight of the cloth (1) is especially 100-300 g/m2> and its thickness is 0.1-3.0 mm. The perforations are uniformly distributed. They are round or especially oval.
Participants receive a combination of paclitaxel 175 mg/m\^2 on Day 1 of each 3-week cycle (Q3W) and carboplatin AUC 5 or 6 on Day 1 Q3W for 6 cycles (up to approximately 4 months). Participants who experience a severe hypersensitivity reaction to paclitaxel or an adverse event (AE) requiring discontinuation of paclitaxel may receive docetaxel 75 mg/m\^2 in place of paclitaxel on Day 1 Q3W after Sponsor consultation. Participants who experience a severe hypersensitivity reaction to carboplatin or an AE requiring discontinuation of carboplatin may receive cisplatin 75 mg/m\^2 in place of carboplatin on Day 1 Q3W after Sponsor consultation.
Baseline experimental measurements will be collected for each individual participant twice prior to zinc supplementation (0 month and 3 month time points). After zinc supplementation, experimental measurements will be collected for each individual participant at the 6 month and 9 month time points. The zinc intervention is zinc picolinate 15 mg once per day for 6 months.
BACKGROUND: Vertebral artery dissection (VAD) is an infrequent source of subarachnoid hemorrhage (SAH), with a high mortality rate, primarily due to the risk of rebleeding both before and after medical intervention. This paper provides a comprehensive analysis of the anatomy, pathophysiology, clinical presentation, treatment strategies, and outcomes of intracranial vertebral artery dissections that result in subarachnoid hemorrhage.
METHODS: Comprehensive five-year literature review (2018-2022) and a retrospective analysis of patient records from our institution between 2016 and 2022. We included studies with a minimum of 5 patients.
RESULTS: The study incorporated ten series from the literature and 22 cases from CHUM. Key anatomical factors increasing the risk of VAD include the vertebral artery's origin from the aortic arch, asymmetry of the vertebral artery, and its tortuosity. Patients may display specific collagen and genetic abnormalities. The occurrence of VAD appears to be more prevalent in men. Those with a ruptured intracranial VAD typically show prodromal symptoms and present with severe SAH. Rebleeding within the first 24 h is frequent. While standard imaging methods are usually adequate for VAD diagnosis, they may not provide detailed information about the perforator anatomy. Treatment approaches include both deconstructive and reconstructive methods.
CONCLUSION: Ruptured VAD is a critical, life-threatening condition. Many patients have a poor neurological status at presentation, and rebleeding prior to treatment is a significant concern. Deconstructive techniques are most effective in preventing rebleeding, whereas the efficacy of reconstructive techniques needs more investigation.