Stable Gastric Pentadecapeptide BPC 157 Therapy: Effect on Reperfusion Following Maintained Intra-Abdominal Hypertension (Grade III and IV) in Rats.

Given in reperfusion, the use of stable gastric pentadecapeptide BPC 157 is an effective therapy in rats. It strongly counteracted, as a whole, decompression/reperfusion-induced occlusion/occlusion-like syndrome following the worst circumstances of acute abdominal compartment and intra-abdominal hypertension, grade III and grade IV, as well as compression/ischemia-occlusion/occlusion-like syndrome. Before decompression (calvariectomy, laparotomy), rats had long-lasting severe intra-abdominal hypertension, grade III (25 mmHg/60 min) (i) and grade IV (30 mmHg/30 min; 40 mmHg/30 min) (ii/iii), and severe occlusion/occlusion-like syndrome. Further worsening was caused by reperfusion for 60 min (i) or 30 min (ii/iii). Severe vascular and multiorgan failure (brain, heart, liver, kidney, and gastrointestinal lesions), widespread thrombosis (peripherally and centrally) severe arrhythmias, intracranial (superior sagittal sinus) hypertension, portal and caval hypertension, and aortal hypotension were aggravated. Contrarily, BPC 157 therapy (10 µg/kg, 10 ng/kg sc) given at 3 min reperfusion times eliminated/attenuated venous hypertension (intracranial (superior sagittal sinus), portal, and caval) and aortal hypotension and counteracted the increases in organ lesions and malondialdehyde values (blood ˃ heart, lungs, liver, kidney ˃ brain, gastrointestinal tract). Vascular recovery promptly occurred (i.e., congested inferior caval and superior mesenteric veins reversed to the normal vessel presentation, the collapsed azygos vein reversed to a fully functioning state, the inferior caval vein-superior caval vein shunt was recovered, and direct blood delivery returned). BPC 157 therapy almost annihilated thrombosis and hemorrhage (i.e., intracerebral hemorrhage) as proof of the counteracted general stasis and Virchow triad circumstances and reorganized blood flow. In conclusion, decompression/reperfusion-induced occlusion/occlusion-like syndrome counteracted by BPC 157 therapy in rats is likely for translation in patients. It is noteworthy that by rapidly counteracting the reperfusion course, it also reverses previous ischemia-course lesions, thus inducing complete recovery.

Stable Gastric Pentadecapeptide BPC 157 Therapy for Primary Abdominal Compartment Syndrome in Rats.

Recently, the stable gastric pentadecapeptide BPC 157 was shown to counteract major vessel occlusion syndromes, i.e., peripheral and/or central occlusion, while activating particular collateral pathways. We induced abdominal compartment syndrome (intra-abdominal pressure in thiopental-anesthetized rats at 25 mmHg (60 min), 30 mmHg (30 min), 40 mmHg (30 min), and 50 mmHg (15 min) and in esketamine-anesthetized rats (25 mmHg for 120 min)) as a model of multiple occlusion syndrome. By improving the function of the venous system with BPC 157, we reversed the chain of harmful events. Rats with intra-abdominal hypertension (grade III, grade IV) received BPC 157 (10 µg or 10 ng/kg sc) or saline (5 ml) after 10 min. BPC 157 administration recovered the azygos vein via the inferior-superior caval vein rescue pathway. Additionally, intracranial (superior sagittal sinus), portal, and caval hypertension and aortal hypotension were reduced, as were the grossly congested stomach and major hemorrhagic lesions, brain swelling, venous and arterial thrombosis, congested inferior caval and superior mesenteric veins, and collapsed azygos vein; thus, the failed collateral pathway was fully recovered. Severe ECG disturbances (i.e., severe bradycardia and ST-elevation until asystole) were also reversed. Microscopically, transmural hyperemia of the gastrointestinal tract, intestinal mucosa villi reduction, crypt reduction with focal denudation of superficial epithelia, and large bowel dilatation were all inhibited. In the liver, BPC 157 reduced congestion and severe sinusoid enlargement. In the lung, a normal presentation was observed, with no alveolar membrane focal thickening and no lung congestion or edema, and severe intra-alveolar hemorrhage was absent. Moreover, severe heart congestion, subendocardial infarction, renal hemorrhage, brain edema, hemorrhage, and neural damage were prevented. In conclusion, BPC 157 cured primary abdominal compartment syndrome.

Corrigendum: Stable Gastric Pentadecapeptide BPC 157 Therapy for Primary Abdominal Compartment Syndrome in Rats.

[This corrects the article DOI: 10.3389/fphar.2021.718147.].

Sensitivity and Specificity of Fenyö-Lindberg and Teicher Scores in the Diagnosis of Acute Appendicitis in Women

The aim of the study was to assess diagnostic accuracy (sensitivity and specificity) of Fenyö-Lindberg and Teicher scores for distinguishing patients that need immediate surgical treatment from the others, in a female population from an urban setting. The study prospectively included 130 female patients admitted to the emergency department with abdominal pain indicating acute appendicitis. The scores and parameters of validity were calculated and compared to definitive diagnosis. For Fenyö-Lindberg score of -17 or less, 84.5% sensitivity, 55.6% specificity, 87.9% positive predictive value (PPV) and 48.4% negative predictive value (NPV) were recorded. For cut-off value greater or equal to -2, there was 59.2% sensitivity, 77.8% specificity, 91% PPV and 33.3% NPV. The Receiver Operating Characteristic (ROC) curve analysis of Fenyö-Lindberg score showed that the best single cut-off value for discriminating acute appendicitis in the study population was -15. For Teicher score, values greater than -3 yielded 89.3% sensitivity and 22.2% specificity, 81.4% PPV and 35.3% NPV. In conclusion, Fenyö-Lindberg score could be used as an additional tool to exclude appendicitis and avoid unnecessary appendectomies. Teicher score may help in recognizing patients with appendicitis. None of the two scores can indicate or decline appendectomy in all cases. Scoring systems may be useful for pointing to important clinical signs and symptoms in specific subpopulations.

Vascular cognitive impairment in diabetes mellitus: are prevention and treatment effective?

Vascular dementia is caused by progressive atherosclerosis leading to multiple small strokes and subsequent brain damage. Approximately 10%-20% of all cases of dementia are attributed to vascular dementia. The 5-year survival rate is 39% for patients with vascular dementia compared with 75% for age-matched controls. It is a growing public health concern because of the lack of effective curative treatment options and rising global prevalence. Duration of diabetes mellitus of 10 years or longer, onset of diabetes before age 65, treatment with insulin and oral antidiabetic medications, and presence of diabetes complications have an impact on the incidence of vascular dementia. On the other hand, patients who suffered stroke either had or are later diagnosed with diabetes (16%-24%). Treatment of vascular dementia in diabetes patients rests on a two-pronged approach: modification of the underlying disease and prevention and treatment of dementia symptoms.

Significance of surgery for prognosis of GIST in cohort from transitional healthcare settings.

OBJECTIVE: Despite significant improvement in survival of gastrointestinal stromal tumors (GIST) due to use of tyrosine kinase inhibitors, surgery still represents the important part of clinical management. The aim of our study was to retrospectively analyze prognosis of GIST depending on the success of surgical treatments and utilization of chemotherapy in transitional country with relatively limited resources. METHODS: cohort of consecutive patients operated for GIST in tertiary medical center, within time frame 1999-2012. RESULTS: 54 patients, in age range 20-85 years (63.3 ± 14.7), male to female ratio 28 (51.9%):26 (48.1%), respectively. Complete excision with clean resection margins (R0) was obtained in 44 (81.5%)of total patients i.e. 44/47 (93.6%) of localized GISTs. Mean follow up was 3.9 ± 3.3 years and 19 patients (35.2%) received imatinib. Rate of overall survival was 40 (74.1%), disease-free survival 31 (57.4%) and 20 (37.0%) experienced recidivism. Follow-up parameters showed significant difference in connection with utilization of imatinib, completeness of resection and existence of metastatic disease (all p < 0.05). ROC analyzes revealed critical value of Ki-67 > 9% as significant predictor of long-term mortality; sensitivity 64.3% [95%CI = 35.1-87.2]; specificity 75.0% [58.8-87.3]; (AUC = 0.693; p = 0.049). CONCLUSION: Rate of complete resections in studied sample of patients from transitional background was overall peer comparable with reports from the developed countries. On the other hand, relatively dominant prognostic position of surgical treatments might be consequence of limited utilization of adjuvant treatment with tyrosine kinase inhibitors.

Peripheral facial weakness (Bell's palsy).

Peripheral facial weakness is a facial nerve damage that results in muscle weakness on one side of the face. It may be idiopathic (Bell's palsy) or may have a detectable cause. Almost 80% of peripheral facial weakness cases are primary and the rest of them are secondary. The most frequent causes of secondary peripheral facial weakness are systemic viral infections, trauma, surgery, diabetes, local infections, tumor, immune disorders, drugs, degenerative diseases of the central nervous system, etc. The diagnosis relies upon the presence of typical signs and symptoms, blood chemistry tests, cerebrospinal fluid investigations, nerve conduction studies and neuroimaging methods (cerebral MRI, x-ray of the skull and mastoid). Treatment of secondary peripheral facial weakness is based on therapy for the underlying disorder, unlike the treatment of Bell's palsy that is controversial due to the lack of large, randomized, controlled, prospective studies. There are some indications that steroids or antiviral agents are beneficial but there are also studies that show no beneficial effect. Additional treatments include eye protection, physiotherapy, acupuncture, botulinum toxin, or surgery. Bell's palsy has a benign prognosis with complete recovery in about 80% of patients, 15% experience some mode of permanent nerve damage and severe consequences remain in 5% of patients.

Cystic lymphangioma of jejunal mesentery mimicking acute appendicitis: case report.

Cystic lymphangiomas of the small bowel mesentery are rare manifestations of intra-abdominal tumors. Usually, they are discovered incidentally during examination for an unrelated abdominal illness. We present a case of a 4-year-old boy who was admitted to our hospital because of the right lower quadrant acute abdominal pain suspect of acute appendicitis. At laparotomy, a giant, cystic, encapsulated and lipomatous mesenterial mass was found, 15 x 15 x 10 cm in size, infiltrating the jejunum. The tumor was located 70 cm from Treitz's ligament. Extirpation of tumor mass with intestinal resection of the involved loops was necessary. Pathologic examination confirmed the diagnosis of mesenteric cystic lymphangioma. Although they are rare, cystic mesenteric lymphangiomas should be considered as a possible cause of acute abdomen and treated with surgical resection. Prognosis after surgical removal is excellent.

Anderson-Fabry disease: developments in diagnosis and treatment.

Fabry disease (Anderson-Fabry disease) is an X-linked recessive lysosomal storage disorder resulting from deficient activity of lysosomal hydrolase, alpha-galactosidase A (alpha-Gal A), which leads to progressive accumulation of globotriaosylceramide (Gb3) in various cells, predominantly endothelial and vascular smooth muscle cells, with clinical manifestations affecting major organs including the central nervous system. The incidence has been estimated to 1 per 40,000-60,000 males and 1 per 117,000 in the general population. Symptoms usually occur during childhood or adolescence, occasionally in middle age (according to the level of the enzyme activity). Life-threatening complications often develop in untreated patients. In classic Fabry disease, they include cutaneous, renal, cardiac and cerebrovascular manifestations that lead to premature death. Early recognition of symptoms, enzyme activity levels, concentration of Gb3 levels in the blood, urine and skin biopsies, as well as genetic testing (GLA gene) enable establishment of early diagnosis and therapeutic intervention with enzyme replacement therapy. Early therapy initiation prior to significant disease manifestations or complications may improve patient outcome.