COVID-19: identifying the main outcome predictors. A retrospective cohort study in Northern Italy.

OBJECTIVE: The need for efficient drugs and early treatment of patients with SARS-CoV-2 infection developing COVID-19 symptoms is of primary importance in daily clinical practice and it is certainly among the most difficult medical challenges in the current century. Recognizing those patients who will need stronger clinical efforts could effectively help doctors anticipate the eventual need for intensification of care (IoC) and choose the best treatment in order to avoid worse outcomes. PATIENTS AND METHODS: We enrolled 501 patients, consecutively admitted to our two COVID hospitals, and collected their clinical, anamnestic and laboratory data on admission. The aim of this retrospective study was to identify those data that are strictly associated with COVID-19 outcomes (IoC and in-hospital death) and that could somehow be intended as predictors of these outcomes. This allowed us to provide a "sketch" of the patient who undergoes, more often than others, an intensification of care and/or in-hospital death. RESULTS: Males were found to have a double risk of needing an IoC (OR=2.11) and a significant role was played by both the PaO2/FiO2 ratio on admission (OR=0.99) and serum LDH (OR=1.01). The main predictors of in-hospital death were age (OR=1.08) and the PaO2/FiO2 ratio on admission (OR=0.99). CONCLUSIONS: Male patients with high serum LDH on admission are those who undergo more often an intensification of care among COVID-19 inpatients. Both age and respiratory performances on admission modify the prognosis within the hospitalization period.

[Isolated jejunal rupture after closed thoraco-abdominal trauma]. / Rottura isolata del digiuno dopo trauma chiuso toraco-addominale.

INTRODUCTION: Short bowel disruption following blunt abdominal trauma is rare and hard to diagnose and to treat. Death rate depends both on timing of surgical procedure and on associated lesions. MATERIAL AND METHODS: We show a case of short bowel isolated lesion following fall from mountain bike, III degree in O.I.S. Classification. Abdominopelvic US and helicoidal CT scan were performed, reveling pneumoperitonaeum due to hollow viscus disruption. Surgical procedure was performed within five hours from trauma. RESULTS: No complications occurred in postoperative period. Upper alimentary tract X-ray proved a regular transit, without any fistula. Patient was discharged on 13th day. CONCLUSION: Laparotomy must not be delayed if there is any doubt about bowel conditions: it's demonstrated that timing of surgical procedure is related to prognosis. If haemodynamic status of the patient allows, careful abdomen CT evaluation is mandatory; adequate nutritional support in postoperative period is also very important.

Endorectal sonographic appearances of rectal MALT lymphoma, its response to therapy, and local recurrence.

Endorectal sonography may significantly help to evaluate rectal lymphoma. We report the sonographic findings in a case of rectal non-Hodgkin's MALT (mucosa-associated lymphoid tissue) lymphoma, including the monitoring of response to therapy and confirmation of recurrence, in a 45-year-old man. On endorectal sonography of the rectal wall, the mucosa was markedly thickened to 1.1 cm and was diffusely hypoechoic and risen into multiple polypoid folds. The submucosa and muscularis propria appeared normal. Multiple lymph nodes were visualized in the perirectal fat; they were homogeneously hypoechoic, were round or oval, and ranged from 1.0 cm to 2.6 cm. Endoscopic biopsies revealed a grade I non-Hodgkin's MALT lymphoma. Following chemotherapy, endorectal sonography showed that the surface of the rectal mucosa had a smoother appearance and near-normal thickness, but lymph nodes, although smaller, remained visible in the perirectal fat. Four months later, endorectal sonography demonstrated a local relapse of disease, with significant thickening of the rectal mucosa and multiple lymph nodes visible in the perirectal fat. Following high-dose chemotherapy for the recurrence, endorectal sonography demonstrated a near-normal appearance of the rectal mucosa.

Proton motive force drives the interaction of the inner membrane TolA and outer membrane pal proteins in Escherichia coli.

The Tol-Pal system of the Escherichia coli envelope is formed from the inner membrane TolQ, TolR and TolA proteins, the periplasmic TolB protein and the outer membrane Pal lipoprotein. Any defect in the Tol-Pal proteins or in the major lipoprotein (Lpp) results in the loss of outer membrane integrity giving hypersensitivity to drugs and detergents, periplasmic leakage and outer membrane vesicle formation. We found that multicopy plasmid overproduction of TolA was able to complement the membrane defects of an lpp strain but not those of a pal strain. This result indicated that overproduced TolA has an envelope-stabilizing effect when Pal is present. We demonstrate that Pal and TolA formed a complex using in vivo cross-linking and immunoprecipitation experiments. These results, together with in vitro experiments with purified Pal and TolA derivatives, allowed us to show that Pal interacts with the TolA C-terminal domain. We also demonstrate using protonophore, K+ carrier valinomycin, nigericin, arsenate and fermentative conditions that the proton motive force was coupled to this interaction.

Usefulness of endorectal ultrasound after preoperative radiotherapy in rectal cancer: comparison between sonographic and histopathologic changes.

PURPOSE: Our aim was to assess the advantages of endorectal ultrasound after preoperative radiotherapy in rectal cancer, its reliability in tumoral staging, and its capacity to identify completely sterilized lesions. METHODS: From 1994 to 1997, 29 patients with rectal cancer were systematically subjected to endorectal ultrasound before and after preoperative radiotherapy. Each patient was administered 30 to 50 Gy, followed by surgery six to eight weeks after completion of radiotherapy. Endorectal ultrasound was performed using a biplanar (linear and sectorial) endorectal probe. The morphologic, quantitative, and echo-pattern changes of the irradiated tumor were examined. Results of ultrasound findings before and after radiotherapy and a histologic examination of the surgical specimens were compared. Histopathologic studies were used to evaluate macromicroscopical radiation-induced changes, case by case. A comparison between tumoral shrinkage and fibrotic replacement was made using the semiquantitative Dworak's method. RESULTS: Morphologically and quantitatively, postradiation endorectal ultrasound showed the reappearance of anatomic cleavage planes, a considerable shrinkage of the tumor, and in low rectal tumors, an increase in the distance from the anorectal ring in more than 50 percent of the cases. These data had a direct influence on surgical treatment. Histologic examination showed that, in 28 out of 29 cases, fibrosis was the most dominant component of the irradiated lesions, varying by more than 50 to 100 percent of the lesion (four cases pTO). A comparison of postradiation endorectal ultrasound with histopathology revealed that fibrosis became the morphologic basis of ultrasound images; therefore, after radiotherapy, what endorectal ultrasound staged was no longer the tumor but the extent of fibrosis in the rectal wall. A histopathologic examination showed that the residual tumor, when present, was always within the fibrosis, never outside or separate from it. Postradiation endorectal ultrasound showed echo-pattern changes. Some of the changes (more echogenic and nonhomogeneous lesions) were histologically related to the persistence of the tumor to a considerable degree; other changes (reappearance of parietal layers) were related to complete sterilization of lesions in two of three cases. CONCLUSIONS: From the morphologic and quantitative point of view, postradiation endorectal ultrasound provides oncologists and surgeons useful information to assess treatment effectiveness and plan the surgical approach. From the tumor staging point of view, our report presents a completely new concept: that six to eight weeks after radiotherapy, endorectal ultrasound no longer stages the tumor, but rather the fibrosis that takes its place. However, postradiation endorectal ultrasound is a valid tool, because the extent of fibrosis in the rectal wall is a direct indication of the depth of residual cancer. A residual tumor, when present, is always inside the fibrosis. Finally, however, as regards the capacity of endorectal ultrasound to exclude or indicate complete sterilization of the lesion, the actual significance of the echo-pattern changes we observed needs to be assessed further by studies on a large number of cases.

Escherichia coli tol-pal mutants form outer membrane vesicles.

Mutations in the tol-pal genes induce pleiotropic effects such as release of periplasmic proteins into the extracellular medium and hypersensitivity to drugs and detergents. Other outer membrane defective strains such as tolC, lpp, and rfa mutations are also altered in their outer membrane permeability. In this study, electron microscopy and Western blot analyses were used to show that strains with mutations in each of the tol-pal genes formed outer membrane vesicles after growth in standard liquid or solid media. This phenotype was not observed in tolC and rfaD cells in the same conditions. A tolA deletion in three different Escherichia coli strains was shown to lead to elevated amounts of vesicles. These results, together with plasmid complementation experiments, indicated that the formation of vesicles resulted from the defect of any of the Tol-Pal proteins. The vesicles contained outer membrane trimeric porins correctly exposed at the cell surface. Pal outer membrane lipoprotein was also immunodetected in the vesicle fraction of tol strains. The results are discussed in view of the role of the Tol-Pal transenvelope proteins in maintaining outer membrane integrity by contributing to target or integrate newly synthesized components of this structure.

[Preoperative radiotherapy in cancer of the rectum. Our 5-year experience]. / La radioterapia preoperatoria nel cancro del retto. La nostra esperienza di 5 anni.

Since 1990, 41 patients with rectal carcinoma have been submitted to preoperative radiotherapy, which induced a shrinkage of the tumor, favouring its surgical resection. Besides, in 3 cases the operative specimens were tumor free, and a higher incidence of A and B 1 categories was found. Surgical results have been compared with an analogous group of 20 patients, where surgery was performed as a first procedure, then followed by radiotherapy in 9. No increase of postoperative complications was observed. While analysis of follow-up results demonstrates a decrease of tumour recurrence in patients with preoperative radiotherapy, no difference in survival was registered, because of the development of extra-pelvic metastases.

TolA central domain interacts with Escherichia coli porins.

TolA is an inner membrane protein with three domains: a transmembrane N-terminus and periplasmic central and C-terminal domains. The interaction of TolA with outer membrane porins of Escherichia coli was investigated. Western blot analyses of cell extracts with anti-TolA antibodies indicated that TolA forms high molecular weight complexes specifically with trimeric OmpF, OmpC, PhoE and LamB, but not with OmpA. The interaction of purified TolA domains with purified porins was also studied. TolA interacted with OmpF, PhoE and LamB porins via its central domain, but not with either their denatured monomeric forms or OmpA. Moreover, the presence or absence of lipopolysaccharides associated with trimeric porins did not modify the interactions. These results suggest that the specific interaction of TolA with outer membrane porins might be relevant to the function of Tol proteins.

[Prosthesis and emergency surgery of hernia]. / Prothèse et chirurgie herniaire en urgence.

Use of prostheses in emergency surgery is a controversial issue due to the risk of infection. We report our experience with a series of 31 strangled hernias treated in emergency situations with a polypropylene (n = 29) or a vinyl (n = 2) sheath placed in a pre-peritoneal or retro-muscular position. There were three small bowel resections and 13 resections of the omentum for necrosis. There were no cases of infectious complications during the post-operative period. There were no recurrent hernias during the follow-up. The absence of any supplementary morbidity after emergency prosthesis is in agreement with the data in the literature. These results suggest that a prosthesis can be proposed for strangled hernias when the weakness of the parietal wall would compromise a conventional procedure. Excluded are cases with severe infection, including peritonitis by gangrenous perforation of an incarcerated loop and associated colonic resections.

[A rare case of primary abdominal actinomycosis]. / Un raro caso di actinomicosi addominale primitiva.

The authors describe a case of primary abdominal actinomycosis operated on because of peritonitis sustained by a tubo-ovarian abscess. They discuss the pathogenesis of the case: the patient had been on intrauterine device contraception till two months earlier and had been operated on for breast cancer. Preoperative diagnosis is quite impossible and only the microscopic observation of the specimen can show the causative agent. Surgical options are reported, stressing the need for an adequate period of antimicrobial therapy.

PIP: In September 1993 a 43-year-old female patient with cancer underwent left mastectomy followed by immediate reconstruction. 6 days passed without problems, but then she presented at the emergency ward with abundant exudation of serous material from the cicatrices. Microbiological test showed evidence of Staphylococcus epidermitis. Drainage of the skin and smooth muscle was performed and the secretion was immediately reduced and seemed to disappear in a short time. In the next 3 days fever arose accompanied by abdominal pain. Blood test showed leucocytosis (24,500 GB), increase of the suppressor lymphocytes (CD8) and the reduction of CD4/CD8 ratio. Abdominal-pelvic echogram showed evidence of an enlarged right adnexum as well as that of the homolateral tube, but no discharge of fluid in the pelvic cavity. Gynecological examination in this patient, who had worn an IUD two months prior, excluded lesions in the portio or vagina and the vaginal flora did not show fungi or parasites. Diagnostic laparoscopy followed, which demonstrated in the pelvic cavity a large para-uterine tumefaction. The pelvic organs were adhering to the parietal layer of the peritoneum and in the whole peritoneal cavity, including the interhepatic-diaphragmatic space, fibrin plaque and pus was observed. Laparotomy was performed, which confirmed a parauterine mass and a tubo-ovarian complex with numerous recesses containing fetid, grayish pus. Complete right adnexectomy was carried out with abundant lavage and multiple drainage of the peritoneal cavity. Subsequently, the abdominal situation improved, but a new examination of drained liquid showed the presence of cutaneous bacterial flora but no fungi or parasites. Ovarian actinomycotic abscess with acute peritonitis and salpingitis was demonstrated. Subsequent antibiotic therapy consisted of piperacilline for 15 days, and 4 months after the episode the patient was well without return of the foci of infection.

[Effect of menstrual cycle on the immune response to surgical stress]. / Effetto del ciclo mestruale sulla risposta immunitaria all'aggressione chirurgica.

The Authors have studied the effects of different surgical interventions on some factors of humoral and cell-mediated immuno-competence: 112 premenopausal women, operated on mainly for benign conditions, have been considered in order to evaluate the influence of various phases of menstrual cycle on surgical immunosuppression. Two schemes were used to stratify the study sample: in the first analysis, we have subdivided the patients in 59 cases in perimenstrual phase (0 through 6 and 21 through 36 days from last menstrual period, LMP) and 53 in periovulatory (7-20 days from LMP). The second stratification relied on the hormone-dependent phases determined by the putative time of ovulation 14 days after LMP: 51 cases in follicular phase and 61 cases in luteal phase have been considered. Immune parameters have been evaluated before surgery and the day after intervention. The first comparison stresses the worst outcome of immune parameters in patients operated on in the perimenstrual period (CD4, activated lymphocytes and C3 have significantly reduced post-operatively). The second part of the study shows no significant difference in the two groups as to such parametres.

Interaction of salmon glucagon, glucagon-like peptide, and epinephrine in the stimulation of phosphorylase a activity in fish isolated hepatocytes.

The simultaneous addition of epinephrine and salmon glucagon to catfish (Ictalurus melas) and trout (Salmo gairdneri) hepatocytes did not induce greater increases in glycogen phosphorylase a activity and in glucose release than those caused by epinephrine alone. The effects of epinephrine are greater than those of glucagon. Propranolol added to the hormonal pool blocked the epinephrine effects. In trout cells, epinephrine and glucagon-like peptide (GLP) had similar effects and when they were added simultaneously the stimulation of metabolic indices was higher compared to that obtained with either epinephrine or GLP. However, the effects were not additive. In the presence of epinephrine plus GLP the inhibitory effect of propranolol was not evident, due to the effect induced by GLP, on which propranolol was not effective. This may indicate that epinephrine masks the GLP effect. Results could mean that epinephrine and glucagon-family peptides act in catfish and trout hepatocytes through different receptors on the same pathway leading to glycogen phosphorylase a activation.

[Primary transitional-cell carcinoma of the male anterior urethra]. / Carcinoma transizionale primitivo dell'uretra anteriore maschile.

Primary carcinomas of the male anterior urethra account for less than 1% of all urological carcinoma. The majority of these neoplasias develop of the posterior part of the urethra (proximal portion). The most common histotype is the squamous-cellular carcinoma. We have only found 4 other published reports of primary transitional carcinoma of the male anterior urethra. The paper discusses the diagnostic and therapeutic procedures employed in these rare cases.

[Progress in the evaluation of lymphatic involvement in cancer of the rectum: endoscopic rectal lymphoscintigraphy]. / Un passo avanti nella valutazione dell'estensione linfonodale del cancro del retto: la linfoscintigrafia rettale endoscopica.

The preoperative evaluation of lymphatic spread in rectal cancer constitutes a considerable problem. A prospective study including 45 patients operated for rectal cancer, was carried out in order to assess the diagnostic value of a new technique: endoscopic rectal lymphoscintigraphy. The results of the preoperative assessment were compared with histological data according to Dukes' classification (Dukes A/B: 22 cases, Dukes C: 23 cases). Analysis of these results revealed the sensitivity (80%), specificity (73%) and accuracy (80%) of this new technique. If, combined with endorectal ultrasonography, rectal lymphoscintigraphy might play highly significant role in identifying the indications for local excisions of small tumours; similarly, the effect of preoperative radiotherapy might be more thoroughly assessed.

Glycogenolytic action of glucagon-family peptides and epinephrine on catfish hepatocytes.

Glycogenolytic effects of salmon and mammalian glucagons, salmon glucagon-like peptide (GLP) and epinephrine were studied on liver cells isolated from catfish (Ictalurus melas). In spring and summer, salmo-glucagon (3×10(-10) to 3×10(-8) M) was more effective than its mammalian counterpart in the stimulation of glucose release and cAMP synthesis in hepatocytes. GLP was less potent as compared to both glucagons. γ-amylase activity was not affected by the treatment with either glucagon-family peptides or epinephrine.The comparison of the glycogenolytic effects of salmon glucagon to those of epinephrine reveals a greater potency of the latter hormone in the stimulation of cAMP synthesis, glycogen-phosphorylase activity and glucose release. Glycogen content in the liver cells was equally depleted after treatment with both of the two hormones.

Adenylate cyclase of catfish hepatocyte membranes: basal properties and sensitivity to catecholamines and glucagon.

Some characteristics of adenylate cyclase of catfish (Ictalurus melas) liver membranes were studied, and the effects of catecholamines and of glucagon were tested. The enzyme has an optimum temperature of 40 degrees C, and a Km for ATP of 0.16 mM at 30 degrees C, and requires Mg2+ for its activity. The enzyme activity is inhibited with a Ca2+ concentration higher than 5 X 10(-5) M, and enhanced with F- higher than 10(-4) M. The response of adenylate cyclase to GTP is biphasic, with a maximum of activity at 10(-5) M GTP. Catecholamines (epinephrine, norepinephrine, isoproterenol, phenylephrine) enhance cyclase activity. Propranolol inhibits the increase in enzyme activity induced by catecholamines, whereas phentolamine is ineffective. This indicates that catecholamines (phenylephrine included) activate adenylate cyclase through a beta-adrenergic mechanism. Glucagon (mammalian) has a smaller effect than epinephrine in increasing the enzyme activity of catfish hepatocyte membranes. This fact is the opposite of that observed for the cyclase activity of rat liver membranes.

[Acute pulmonary edema due to hyperperfusion: experimental observations in the dog]. / Oedème pulmonaire aigu par hyperafflux: observations expérimentales chez le chien.

A condition of acute pulmonary edema was obtained experimentally in the dog, perfusing the lower lobe of the left lung by a roller pump with compatible canine plasma. The edema develops contemporarily to the increase of pressure in the pulmonary artery and the interstitial tissue: it diffuses principally in the interstitial tissue, while after clamping the pulmonary veins it is observed also inside the alveoli.