Benefit of adjuvant chemotherapy in patients with special histology subtypes of triple-negative breast cancer: a systematic review.

PURPOSE: Breast cancer (BC) is a leading cause of morbidity, disability, and mortality in women, worldwide; triple-negative BC (TNBC) is a subtype traditionally associated with poorer prognosis. TNBC special histology subtypes present distinct clinical and molecular features and sensitivity to antineoplastic treatments. However, no consensus has been defined on the best adjuvant therapy. The aim of the review is to study the evidence from literature to inform the choice of adjuvant treatments in this setting. METHODS: We systematically searched literature assessing the benefit of adjuvant chemotherapy in patients with TNBC special histotypes (PROSPERO: CRD42020153818). RESULTS: We screened 6404 records (15 included). All the studies estimated the benefit of different chemotherapy regimens, in retrospective cohorts (median size: 69 patients (range min-max: 17-5142); median follow-up: 51 months (range: 21-268); mostly in Europe and USA). In patients with early-stage adenoid cystic TNBC, a marginal role of chemotherapy was reported. Similar for apocrine TNBC. Medullary tumors exhibited an intrinsic good prognosis with a limited role of chemotherapy, suggested to be modulated by the presence of tumor-infiltrating lymphocytes. A significant impact of chemotherapy on the overall survival was estimated in patients with metaplastic TNBC. Limitations were related to the retrospective design of all the studies and heterogeneous treatments received by the patients. CONCLUSIONS: There is potential opportunity to consider treatment de-escalation and less intense therapies in some patients with early, special histology-type TNBC. International efforts are indispensable to validate prospective clinical decision models.

Unexpected Mycoplasma hominis infection in two renal transplant recipients traced back to the same donor by whole-genome sequencing.

Mycoplasma hominis is a common colonizer of the lower genitourinary tract. Although its clinical relevance for causing urogenital infections in immunocompetent individuals is controversial, this bacterium has been involved in severe invasive infections in allograft recipients. In this report, we describe two cases of M. hominis infection in two young renal transplant recipients within the first month post-transplant. Although at first no epidemiological link between the two cases had been suspected, whole-genome sequencing (WGS) analysis showed that both isolates were identical, highly suggestive of an origin with the common organ donor.

Donor Specificity but Not Broadness of Sensitization Is Associated With Antibody-Mediated Rejection and Graft Loss in Renal Allograft Recipients.

Panel-reactive antibodies are widely regarded as an important immunological risk factor for rejection and graft loss. The broadness of sensitization against HLA is most appropriately measured by the "calculated population-reactive antibodies" (cPRA) value. In this study, we investigated whether cPRA represent an immunological risk in times of sensitive and accurate determination of pretransplantation donor-specific HLA antibodies (DSA). Five hundred twenty-seven consecutive transplantations were divided into four groups: cPRA 0% (n = 250), cPRA 1-50% (n = 129), cPRA 51-100% (n = 43), and DSA (n = 105). Patients without DSA were considered as normal risk and received standard immunosuppression without T cell-depleting induction. Patients with DSA received an enhanced induction therapy and maintenance immunosuppression. Surveillance biopsies were performed at 3 and 6 months. Median follow-up was 5.7 years. Among the three cPRA groups, there were no differences regarding the 1-year incidence of ABMR (p = 0.16) and TCMR (p = 0.75). The 5-year allograft survival rates were similar and around 87% (p = 0.28). The estimated glomerular filtration rate at last follow-up was 50-53 mL/min (p = 0.45). On multivariable Cox proportional hazard analysis, the strongest independent predictor for ABMR and (death-censored) graft survival was pretransplantation DSA. cPRA were not predictive for ABMR, TCMR, or (death-censored) graft survival. We conclude that with current DSA assignment, the broadness of sensitization measured by cPRA does not imply an immunological risk.

Detection of clinical and subclinical tubulo-interstitial inflammation by the urinary CXCL10 chemokine in a real-life setting.

Urinary CXCL10 is a promising noninvasive biomarker for tubulo-interstitial allograft inflammation, but its diagnostic characteristics have not been assessed in a real-life setting. We investigated urinary CXCL10 in 213 consecutive renal allograft recipients having 362 surveillance biopsies at 3/6 months and 80 indication biopsies within the first year posttransplant. Allograft histology results were classified as (i) acute Banff score zero, (ii) interstitial infiltrates only, (iii) tubulitis t1, (iv) tubulitis t2-3 and (v) isolated vascular compartment inflammation. For clinical and subclinical pathologies, urinary CXCL10 correlated well with the extent of tubulo-interstitial inflammation. To determine diagnostic characteristics of urinary CXCL10, histological groups were separated into two categories: no relevant inflammation (i.e. acute Banff score zero and interstitial infiltrates only) versus all other pathologies (i.e. tubulitis t1-3 and isolated vascular compartment inflammation). For subclinical pathologies, AUC was 0.69 (sensitivity 61%, specificity 72%); for clinical pathologies, AUC was 0.74 (sensitivity 63%, specificity 80%). A urinary CXCL10-guided biopsy strategy would have reduced performance of surveillance and indication biopsies by 61% and 64%, respectively. Missed (sub)clinical pathologies were mostly tubulitis t1 and isolated vascular compartment lesions. In real life, urinary CXCL10 had clinically useful diagnostic properties making it a candidate biomarker to guide allograft biopsies.

Efficacy of induction therapy with ATG and intravenous immunoglobulins in patients with low-level donor-specific HLA-antibodies.

Low-level donor-specific HLA-antibodies (HLA-DSA) (i.e. detectable by single-antigen flow beads, but negative by complement-dependent cytotoxicity crossmatch) represent a risk factor for early allograft rejection. The short-term efficacy of an induction regimen consisting of polyclonal anti-T-lymphocyte globulin (ATG) and intravenous immunoglobulins (IvIg) in patients with low-level HLA-DSA is unknown. In this study, we compared 67 patients with low-level HLA-DSA not having received ATG/IvIg induction (historic control) with 37 patients, who received ATG/IvIg induction. The two groups were equal regarding retransplants, HLA-matches, number and class of HLA-DSA. The overall incidence of clinical/subclinical antibody-mediated rejection (AMR) was lower in the ATG/IvIg than in the historic control group (38% vs. 55%; p = 0.03). This was driven by a significantly lower rate of clinical AMR (11% vs. 46%; p = 0.0002). Clinical T-cell-mediated rejection (TCR) was significantly lower in the ATG/IvIg than in the historic control group (0% vs. 50%; p < 0.0001). Within the first year, allograft loss due to AMR occurred in 7.5% in the historic control and in 0% in the ATG/IvIg group. We conclude that in patients with low-level HLA-DSA, ATG/IvIg induction significantly reduces TCR and the severity of AMR, but the high rate of subclinical AMR suggests an insufficient control of the humoral immune response.

Aliskiren corrects recurrent hyperreninemia and hyperaldosteronism in autosomal dominant polycystic kidney disease.

A 47-year-old woman with family history of autosomal-dominant polycystic kidney disease (ADPKD), who underwent living-donor kidney transplantation in 2000, presented with recurrent edema, hyperreninemia, and hyperaldosteronism. Since 2002, her antihypertensive therapy comprised ramipril and spironolactone. The post-transplantation kidney function was stable. Based on the clinical picture and reports of renin secretion by renal cysts in ADPKD, we performed a trial of aliskiren therapy (300 mg/day). The patient showed excellent blood pressure control and reduction of edema, with aldosterone levels normalizing within 2 months. This is a novel report of aliskiren therapy for treatment of edema, hyperreninemia, and hyperaldosteronism in ADPKD.

Effects of weak/non-complement-binding HLA antibodies on C1q-binding.

It is unknown under what conditions and to what extent weak/non-complement (C)-binding IgG subclasses (IgG2/IgG4) can block C1q-binding triggered by C-binding IgG subclasses (IgG1/IgG3). Therefore, we investigated in vitro C1q-binding induced by IgG subclass mixtures targeting the same HLA epitope. Various mixtures of HLA class II specific monoclonal antibodies of different IgG subclasses but identical V-region were incubated with HLA DRB1*07:01 beads and monitored for C1q-binding. The lowest concentration to achieve maximum C1q-binding was measured for IgG3, followed by IgG1, while IgG2 and IgG4 did not show appreciable C1q-binding. C1q-binding occurred only after a critical amount of IgG1/3 has bound and sharply increased thereafter. When both, C-binding and weak/non-C-binding IgG subclasses were mixed, C1q-binding was diminished proportionally to the fraction of IgG2/4. A 2- to 4-fold excess of IgG2/4 inhibited C1q-binding by 50%. Very high levels (10-fold excess) almost completely abrogated C1q-binding even in the presence of significant IgG1/3 levels that would usually lead to strong C1q-binding. In sensitized renal allograft recipients, IgG subclass constellations with ≥ 2-fold excess of IgG2/4 over IgG1/3 were present in 23/66 patients (34.8%) and overall revealed slightly decreased C1q signals. However, spiking of patient sera with IgG2 targeting a different epitope than the patient's IgG1/3 synergistically increased C1q-binding. In conclusion, if targeting the same epitope, an excess of IgG2/4 is repressing the extent of IgG1/3 triggered C1q-binding in vitro. Such IgG subclass constellations are present in about a third of sensitized patients and their net effect on C1q-binding is slightly inhibitory.

A new clinical scale of carpal tunnel syndrome: validation of the measurement and clinical-neurophysiological assessment.

OBJECTIVE: To validate a new clinical scale of carpal tunnel syndrome (CTS). The scale is based on clinical history and physical examination findings and includes two figures. The first is a score determined by clinical history and objective findings. The second evaluates the presence/absence of pain as a dichotomous categorical score. METHODS: One hundred and sixty-eight consecutive idiopathic CTS hands were studied in two centers (Rome, Siena). We compare the results of the historical-objective scale (Hi-Ob scale) with the results of other validated measurements of CTS severity: (1) the Italian version of the Boston Carpal Tunnel Questionnaire, (2) the neurophysiological classification adopted by the Italian CTS study group. Furthermore, for the Hi-Ob scale the intra-observer and inter-observer evaluations were assessed. RESULTS: The main Hi-Ob parameter was positively related to the conventional validated measurements. Conversely, the category 'PAIN' of the Hi-Ob scale appeared unrelated to the other clinical and electrophysiological parameters. Intra- and inter-observer evaluation showed the reproducibility of the Hi-Ob assessment. CONCLUSIONS: Our data show that the Hi-Ob scale is a reliable measurement which may be useful in CTS evaluation either for clinical or for scientific purposes.

A useful electrophysiological test for diagnosis of minimal conduction block.

OBJECTIVE: To evaluate the usefulness, sensitivity and specificity of a new neurophysiological test for partial conduction block. METHODS. In 17 patients (17 nerves) with clinical pictures strongly suggesting the presence of motor conduction block and 20 healthy subjects (40 nerves), motor nerve conduction studies were performed with the conventional surface technique and with a new technique developed by us: the single fiber EMG (SFEMG) conduction block test. Moreover, we also evaluated patients with other neurological diseases. The recent American Association of Electrodiagnostic Medicine (AAEM) consensus criteria for partial conduction block were used for the standard conduction block tests. RESULTS: According to AAEM consensus criteria, 5/17 cases presented 'definite' partial conduction block and 6 presented 'probable' partial conduction block. In contrast, 16/17 cases (94%) presented evidence of conduction block at the SFEMG conduction block test. The 5/6 cases that did not fulfill in the AAEM criteria and that presented abnormal findings at SFEMG nerve conduction test could be considered affected by minimal conduction block. The sensitivity of this new test was greater than conventional test. The specificity was 100% (no abnormal findings in healthy subjects or patients with diseases other than neuropathy). CONCLUSIONS: The SFEMG conduction block test is a sensitive, complementary, technique for diagnosis of minimal conduction block in patients with normal findings in standard nerve conduction studies.

Quantitative evaluation of insulin antibodies by radiochemical analysis.

A method is described for determining insulin antibodies, and some applications are reported, concerning 45 patients, 30 with diabetic pathology, 15 of them receiving insulin. The diagnostic tool proved useful.

Inhibition of tumor necrosis factor-alpha secretion by pentoxifylline in advanced cancer patients with abnormally high blood levels of tumor necrosis factor-alpha.

TNF, in addition to its antitumor activity, would play an important role in the pathogenesis of cancer-related severe complications, including ARDS and DIC. Therefore, the modulation of TNF secretion could be important in the supportive care of advanced cancer patients. At present, PTX is the only drug which has been proven to be able to inhibit in vitro the release of TNF. The present study was performed to evaluate the effect of PTX on TNF blood concentrations in disseminated cancer patients with abnormally high TNF values. The study included 14 cancer patients, with initial or conclamate signs of ARDS (n = 8) or DIC (n = 6). PTX was given intravenously at a dose of 300 mg/day for 7 days. Mean serum levels of TNF significantly decreased in response to PTX therapy, and they returned to normal range in 5/14 patients. These preliminary data would suggest that PTX may be considered as a biological response modifier, capable of inhibiting TNF secretion in humans, with a following potential use in the treatment of cancer-related severe complications.

Mixed complexes of Ni(2+) or Zn(2+) and citric acid with 2,2'-bipyridyl in aqueous solution.

The stability constants of ternary Ni(2+) or Zn(2+) complexes with 2,2'-bipyridyl and citric acid have been determined by means of pH-titrations at 25.0 +/- 0.2 degrees and an ionic strength of 0.1M (KNO(3)). The stability constants of ternary complexes have been compared with those of similar ternary species.

A prospective imaging study of 131I-B72.3 monoclonal antibody in patients with epithelial ovarian cancer: preliminary report.

Twenty patients with known ovarian cancer have been investigated in this pilot study to verify the clinical usefulness of radioimaging using the B72.3 monoclonal antibody labelled with iodine-131. No adverse reactions occurred after intravenous injection of B72.3 MoAb. The radioimaging results were compared with those obtained with other diagnostic methods, including computed X-ray tomography and ultrasound. A sensitivity of 85% in the detection of primary ovarian cancers and collections of ascites, and of 84% in the detection of abdominal and extraperitoneal metastases has been demonstrated using this radioiodinated antibody in vivo. No false localization occurred. Immunohistochemical studies showed no cross-reactions between B72.3 MoAb and mesothelial cells, confirming the high specificity of binding between B72.3 MoAb and neoplastic cells in ascites. Negligible uptake of radiolabelled B72.3 MoAb has been demonstrated in the unaffected ovary. The major advantage of using this monoclonal antibody is related to the expression of a recognized antigen (called TAG 72) in mucinous, serous and in differentiated adenocarcinomas of the ovary.

Lectin histochemistry of the Drosophila embryo.

A selection of lectins was used to characterise changes in the distribution of glycoconjugates during the embryonic development of Drosophila melanogaster. The blastoderm of pre-gastrulation embryos bound low levels of the lectins LPA, UEA-I and PNA. The germ line progenitors (pole cells) bound ConA, PNA and LPA. The yolk granules, the trachea, and the gut bound GSA-I. All lectins had detectable labeling of the ectoderm. The somata of the nervous system bound ConA and LPA. Electron microscopic analysis of PNA labeling of the nervous system revealed exclusive binding to the axon tracts and ensheathing glia. Hyaluronate lyase digestion of oligosaccharides revealed gut and nervous system binding with WGA and UEA-I. This study revealed useful biochemical probes of gut, epidermal and nervous system development that identify the distribution of likely ligands for as yet uncharacterised endogenous lectins.

Influence of information related to child physical abuse on professional ratings of adjustment and prognosis.

The study investigates the influence of access to information of a history of physical maltreatment on the evaluative responding of social service and clinical psychology professionals. Written vignettes were used in a 2 x 2 x 2 factorial design to manipulate the: (a) presence/absence of abuse history; (b) presence/absence of behavior problems; and (c) gender of the child. Professionals rated children presented in 12 case vignettes along five treatment-related dimensions: (a) overall adjustment; (b) predicted 6 months temporal stability of behavior; (c) likelihood of treatment referral; (d) expected home intervention success; and (e) expected school intervention success. Four dimensions related to social functioning were also rated, including likelihood of the child being: (a) recommended to serve as assistant to teacher; (b) elected as a school activity team leader; (c) elected as a class officer; and (d) nominated as a candidate for successful completion of a summer camp program. The findings verified the influence of information related to a history of maltreatment of professional judgments, despite matched vignette content for all factors other than maltreatment status. The results suggests a possible failure to recognize that some children have been buffered from the negative effects of abuse and point to the risk of erroneous judgments that may be directed toward maltreated children.

[Our experience in pancreatic injuries]. / Nostra esperienza sui traumi pancreatici

Eight cases of pancreatic traumas are considered and the literature reviewed. Personal cases include: 1 contusion treated nedically; 2 cases of complete rupture (1 of which primary treated with double jejunal pancreatic anastomosis); 1 associated with splenic rupture, treated with distal pancreatectomy and splenectomy; 1 contusion of the head associated with hepatic lesions treated with suture of the lesions external derived and cholecystostomy; 4 contusions without lesion of the duct associated with other visceral lesions (stomach, duodenum, spleen, liver), treated surgically by suture of the lesion, and drainage of the omental bursa. As regards diagnosis, the only pathognomonic examination is amylasaemia. Paracentesis proved important in cases of haemoperitoneum. Long-term results were observed by scintigraphy and through starch and maltose load curves. Scintigraphy pointed to the presence of functional deficiency in areas which seemed to be only contused or actually normal. It is therefore concluded, especially in cases of complete rupture, that therapy should be kept as conservative as possible (Duodenal pancreatic anastomosis). The purpose of this is to prevent fistulas of the residual stump, fostered by the pressure in Oddi's sphincter, and to lease the pancreatic tissue as operative as possible. This is particularly important if patients are young.

[Hypertrophy of the gastrocnemius muscles: possible etiology of the popliteal artery entrapment syndrome?]. / Hypertrophie des muscles jumeau: étiologie possible d'un syndrome de l'artère poplitée piégée (SAPP)?

Excessive hypertrophy of the both heads of gastrocnemius has been reported as a possible etiology of a popliteal artery entrapment syndrome. However, this syndrome is rather unusual among all those young adults and athletes with hypertrophied gastrocnemius. An other factor must exist in addition of hypertrophy. We describe a patient presenting a more cranial migration of the both heads of gastrocnemius with a shorter and more proximal tendinous attachment above the femoral epicondyles. Thus, excessive hypertrophy of the both heads of gastrocnemius may be in fact the cause of a popliteal artery entrapment syndrome when there is a congenital abnormality of muscular migration.

[A case of Hallermann-Streiff syndrome with rapidly fatal course]. / Su di un caso di sindrome di Hallermann-Streiff ad evoluzione rapidamente fatale.

The Hallermann-Streiff syndrome is a rare affection characterized by beaked nose, dyscephaly, hypotrichosis, cataracts, micrognathia and proportionate short stature. The most severe complication in the syndrome is respiratory embarrassment. Narrow air passage with abnormal glottic closure, prenatal growth deficiency, immunodeficiency and sometimes associated cardiovascular anomalies, can predispose these patients to pulmonary infections. The Authors describe a new-born with Hallermann-Streiff syndrome, who, after a brief period of obstructive apnea successfully treated with CPAP, developed a severe pulmonary infection that caused his death at the age of 61 days.