Nitric oxide inhibits neonatal hepatocyte oxidative metabolism

BACKGROUND/PURPOSE: Liver function is frequently impaired in neonates with sepsis. Nitric oxide (NO) is thought to be a mediator of organ dysfunction and liver oxidative metabolism during sepsis. The authors developed an in vitro model to investigate the effect of NO and the combined effect of NO plus H2O2 on neonatal hepatocyte oxidative metabolism. METHODS: Hepatocytes were isolated from neonatal rats. Oxygen consumption was measured polarographically. In Study A, cells were exposed to S-Nitroso-N-acetylpenicillamine (SNAP), an NO donor, at various concentrations. In study B, myxothiazol and oligomycin, inhibitors of mitochondrial respiration, were added to investigate the site of action of NO. In study C, hepatocytes were incubated in the presence of both SNAP (300 micromol/L) and H2O2 (1.5 mmol/L). In study D, morphological alterations induced by NO and NO plus H2O2 were investigated by hepatocyte electron microscopy. RESULTS: In study A, SNAP caused a dose-dependent decrease in oxygen consumption. A significant inhibition was reached at 300 micromol/L SNAP. In study B, the lack of further inhibition when SNAP was given together with myxothiazol indicates that NO acts intramitochondrially. Similarly, no further inhibition occurred when the NO donor was given together with oligomycin, suggesting that the effect of NO is mainly at the level of ATP synthase. In study C, concomitant addition of 300 micromol/L SNAP and 1.5 mmol/L H2O2 to hepatocytes caused further inhibition of oxygen consumption compared with either SNAP or H2O2 alone. In study D, mild alterations in hepatocyte morphology were noted in the presence of SNAP or SNAP plus H2O2. CONCLUSIONS: In neonatal hepatocytes, NO significantly inhibits mitochondrial oxygen consumption, possibly at the level of ATP synthase. The effect of NO is additive to that of H2O2. Morphological findings were consistent with these biochemical effects and suggest that NO and H2O2 are important mediators of liver damage during sepsis.     

Characterization of Healthcare-Associated and Community-Associated Clostridioides difficile Infections among Adults,Canada, 2015–2019

We investigated epidemiologic and molecular characteristics of healthcare-associated (HA) and community-associated (CA) Clostridioides difficile infection (CDI) among adult patients in Canadian Nosocomial Infection Surveillance Program hospitals during 2015–2019. The study encompassed 18,455 CDI cases, 13,735 (74.4%) HA and 4,720 (25.6%) CA. During 2015–2019, HA CDI rates decreased by 23.8%, whereas CA decreased by 18.8%. HA CDI was significantly associated with increased 30-day all-cause mortality as compared with CA CDI (p<0.01). Of 2,506 isolates analyzed, the most common ribotypes (RTs) were RT027, RT106, RT014, and RT020. RT027 was more often associated with CDI-attributable death than was non-RT027, regardless of acquisition type. Overall resistance C. difficile rates were similar for all drugs tested except moxifloxacin. Adult HA and CA CDI rates have declined, coinciding with changes in prevalence of RT027 and RT106. Infection prevention and control and continued national surveillance are integral to clarifying CDI epidemiology, investigation, and control.     

Delivering maternal health care services in an internal conflict setting in Maguindanao, Philippines

To improve access to maternal health care and family planning services in conflict-stricken Maguindanao province, southern Philippines, several non-governmental organisations have begun collaborating with local public health services. This exploratory study describes the experiences of local government service providers and two NGOs in a context of long-standing internal armed conflict, how and to what extent provision has been affected by the conflict and what has been done to overcome its effects. It is based on interviews with six health service coordinators and providers. Local government-NGO partnership takes the form of giving NGOs space in government health care facilities and receiving from them critical supplies, personnel and contraceptives. Service delivery structures have generally been spared from direct attacks by the parties involved locally in armed conflict due to the perceived benefits of their services, including for rebels and their families, their neutral stance and willingness to treat everyone. However, they do suffer from occasional disruption and kidnappings and need to seek protection from local leaders. When mass evacuation is required providers follow displaced families to evacuation points to ensure they continue to get services. Collaboration for maternal health care provision is recent, but the planned expansion of NGO projects will help it to evolve.     

Contrast echocardiography: transmission of echoes to the left heart across the pulmonary vascular bed

All available reports indicate that the echoproducing qualityof agents used for contrast echocardiography is lost duringtheir passage through the pulmonary or systemic capillary bed.A technique has been developed to transmit echoes to the leftheart across the pulmonary vascular bed with the use of venouscatheterization. In 43 patients with acquired or congenitalheart disease, a balloon-tipped catheter was wedged in a pulmonaryarterial branch, the balloon was inflated, then rapidly deflatedafter injection of an echoproducing substance, while M-Modeor two-dimensional echocardiograms were recorded. Echoes consistentlyappeared in the left heart following injection of indocyaninegreen (5–10 mg), saline (5 ml) or CO₂ (0.5–1 ml).In 25 patients with a documented left-to-right shunt, echoesalso appeared in the right heart chamber receiving the shunt.There were no false negatives nor false positives. No complicationsor side effects were observed. The presumed mechanism of transmissionis the achievement of a high concentration of echoes and/orbypassing of pulmonary capillaries through physiological intrapidmonaryshunts. The method is proposed as a screening procedure to be used duringright heart catheterization so as to avoid, if possible, theinjection ofradioopaque contrast and the invasion of the leftheart     

COVID-19 vaccine-induced lymphadenopathies: incidence,course and imaging features from an ultrasound prospective study

Aimslymphadenopathy can occur after COVID-19 vaccination and when encountered at ultrasound examinations performed for other reasons might pose a diagnostic challenge. Purpose of the study was to evaluate the incidence, course and ultrasound imaging features of vaccine-induced lymphadenopathy.Methods89 healthy volunteers (median age 30, 76 females) were prospectively enrolled. Vaccine-related clinical side effects (e.g., fever, fatigue, palpable or painful lymphadenopathy) were recorded. Participants underwent bilateral axillary, supraclavicular and cervical lymph node stations ultrasound 1–4 weeks after the second dose and then again after 4–12 weeks in those who showed lymphadenopathy at the first ultrasound. B-mode, color-Doppler assessment, and shear-wave elastography (SWE) evaluation were performed. The correlation between lymphadenopathy and vaccine-related side effects was assessed using the Fisher’s exact test.ResultsPost-vaccine lymphadenopathy were found in 69/89 (78%) participants (37 single and 32 multiple lymphadenopathy). Among them, 60 presented vaccine-related side effects, but no statistically significant difference was observed between post-vaccine side effect and lymphadenopathy. Ultrasound features of vaccine-related lymphadenopathy consisted of absence of fatty hilum, round shape and diffuse or asymmetric cortical thickness (median cortical thickness of 5 mm). Vascular signal was mainly found to be increased, localized in both central and peripheral regions. SWE showed a soft cortical consistence in all cases (median value 11 Kpa). At follow-up, lymph-node morphology was completely restored in most cases (54/69, 78%) and in no case lymphadenopathy had worsened.ConclusionA high incidence of vaccine-induced lymphadenopathy was found in a population of healthy subjects, with nearly complete regression within 4–12 weeks.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40477-022-00674-3.     

Nontraumatic osteonecrosis of the humeral head

The humeral head is the second most common site for nontraumatic osteonecrosis after the femoral head, yet it has attracted relatively little attention. Osteonecrosis is associated with many conditions, such as corticosteroid use, sickle-cell disease, alcoholism, dysbarism (or caisson disease), Gaucher's disease, and other systemic conditions. The diagnosis is a clinical and radiographic one, the latter forming the basis for its staging. Treatment depends on the chronicity and severity of symptoms, as well as the degree of clinical and radiographic progression. Surgical treatment includes arthroscopic debridement and core decompression for early osteonecrosis and hemiarthroplasty or total shoulder arthroplasty for more advanced disease. This report reviews osteonecrosis of the humeral head, with an emphasis on current treatment options.     

Shoulder arthroplasty for the treatment of the sequelae of fractures of the proximal humerus

The purpose of this multicenter study was to analyze the results of shoulder arthroplasty for the treatment of the sequelae of proximal humerus fractures and establish an updated classification system and treatment guidelines for these complex situations. Seventy-one sequelae of proximal humerus fractures were treated with shoulder replacement with the use of the same nonconstrained, modular, and adaptable prosthesis: the Aequalis prosthesis (Tornier Inc, St Ismier, France). The average time between initial fracture and shoulder arthroplasty was 5 years and 5 months. On the basis of anatomic classification schemes, sequelae were divided into 4 types: type 1, humeral head collapse or necrosis with minimal tuberosity malunion (40 cases); type 2, locked dislocations or fracture-dislocations (9 cases); type 3, nonunions of the surgical neck (6 cases); and type 4, severe malunions of the tuberosities (16 cases). The mean postoperative follow-up was 19 months (range, 12 to 48 months). Overall, the postoperative Constant score was excellent in 11 cases (16%), good in 19 cases (26%), fair in 18 cases (25%), and poor in 23 cases (33%). There were 18 complications (27%). Fifty-nine of 70 patients (81%) stated that they were satisfied with the result. The most significant factor affecting functional outcome was greater tuberosity osteotomy (P <.005). Regarding both surgical treatment and postoperative prognosis, we identify 2 categories of proximal humerus fracture sequelae: category 1, intracapsular/impacted fractures sequelae (associated with both cephalic collapse or necrosis [type 1] and chronic dislocation or fracture-dislocation [type 2]), in which an articulating joint can be reconstructed without a greater tuberosity osteotomy; and category 2, extracapsular/disimpacted fractures sequelae (associated with both surgical neck nonunions [type 3] and severe tuberosity malunions [type 4]) where the proximal humerus cannot be reconstructed without a greater tuberosity osteotomy. All of the excellent and good postoperative Constant scores were obtained in type 1 and 2, in which osteotomy of the greater tuberosity was not required. All patients in type 3 and 4, who underwent a greater tuberosity osteotomy, had either fair or poor results and did not regain active elevation above 90 degrees. We conclude that a greater tuberosity osteotomy is the most likely reason for poor and unpredictable results after shoulder replacement arthroplasty for the treatment of the complex sequelae of proximal humerus fractures. Shoulder arthroplasty for the treatment of the sequelae of fractures of the proximal humerus should be performed without an osteotomy of the greater tuberosity when possible. If prosthetic replacement is possible without an osteotomy, surgeons should accept the distorted anatomy of the proximal humerus and adapt the prosthesis and their technique to the modified anatomy. A modular and adaptable prosthesis with both adjustable offsets and inclination may allow surgeons to adapt to a large number of malunions and may help to avoid the troublesome greater tuberosity osteotomy in a higher proportion of cases.