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Background Low-volume hypertonic solutions, such as half-molar lactate (LAC), may be a potential treatment used for fluid resuscitation. This study aimed to evaluate the underlying cardiovascular effects and mechanisms of LAC infusion compared to sodium-matched hypertonic sodium chloride (SAL). Methods Eight healthy male participants were randomized in a controlled, single-blinded, crossover study. Each participant received a four-hour infusion of LAC and SAL in a randomized order. Assessor-blinded echocardiography and blood samples were performed. The primary endpoint was cardiac output (CO) measured by echocardiography. Results During LAC infusion, circulating lactate levels increased by 1.9 mmol/L (95% CI 1.8–2.0 mmol/L, P  < 0.001) compared with SAL. CO increased by 1.0 L/min (95% CI 0.5–1.4 L/min, P  < 0.001), driven primarily by a significant increase in stroke volume of 11 mL (95% CI 4–17 mL, P  = 0.002), with no significant change in heart rate. Additionally, left ventricular ejection fraction improved by 5 percentage points ( P  < 0.001) and global longitudinal strain by 1.5 percentage points ( P  < 0.001). Preload indicators were elevated during SAL infusion compared with LAC infusion. Concomitantly, afterload parameters, including systemic vascular resistance and effective arterial elastance, were significantly decreased with LAC infusion compared with SAL, while mean arterial pressure remained similar. Indicators of contractility improved during LAC infusion. Conclusions In healthy participants, LAC infusion enhanced cardiac function, evidenced by increases in CO, stroke volume, and left ventricular ejection fraction compared with SAL. Indicators of contractility improved, afterload decreased, and preload remained stable. Therefore, LAC infusion may be an advantageous resuscitation fluid, particularly in patients with cardiac dysfunction. Clinical trial registrations https://clinicaltrials.gov/ct2/show/NCT04710875 . Registered 1 December 2020.

Bacterial vaginosis (BV) is associated with an elevated vaginal pH and the presence of abnormal offensive discharge. It is common, often recurrent, and the most effective treatment regimen is unknown. 'Metronidazole Versus lactic acId for Treating bacterial vAginosis' (VITA) is a UK-based randomised controlled trial assessing clinical and cost-effectiveness of topical lactic acid gel compared to oral metronidazole antibiotic for treating second and subsequent BV episodes. Few BV trials report on women's preferences for treatment in the context of their own experiences. This qualitative study investigated the acceptability and tolerability of the two treatments. During the trial, semi-structured telephone interviews were undertaken between January-May 2018. A total of 33 women diagnosed with BV were consecutively sampled then interviewed from six sites across England. Thematic analysis was guided by the acceptability of health interventions framework. Potential causes of BV and its impact on women's lives were explored in addition to women's treatment preference and perceived treatment effectiveness. Although women felt antibiotics treat BV effectively, and were associated with longer time periods between episodes, they generally preferred using the lactic acid gel because of ease of use, once daily application and less side-effects. Women would recommend the lactic acid gel to others for mild cases of BV but to take antibiotics when more severe. The risk of antibiotic drug resistance was a common concern. Self-help medicating or self-decision to not treat was also evident due to prior experience of poor outcomes from treatment. Triggers of BV were attributed to personal hygiene habits-soaps used to wash the vagina and sexual practices such as unprotected sex. Acceptability and preference for topical lactic acid gel or oral metronidazole tablets in the treatment of recurrent BV was affected by personal choice relating to affective attitude, burden, ethicality, intervention coherence, opportunity costs, and self-efficacy. These differed depending on ease of use, tolerability and past experiences, but not necessarily based on perceived drug effectiveness. Knowledge of a patient preference for topical lactic acid gel therapy despite lower perceived effectiveness may be useful for clinicians when making treatment decisions.

Background Alveolar Bone loss occurs frequently during the first six months after tooth extraction. Various studies have proposed different methods to reduce as much as possible the atrophy of the alveolar ridge after tooth extraction. Filling the socket with biomaterials after extraction can reduce the resorption of the alveolar ridge. We compared the height of the alveolar process at the mesial and distal aspects of the extraction site and the resorption rate was calculated after the application of HA/β-TCP or synthetic co-polymer polyglycolic - polylactic acid PLGA mixed with blood to prevent socket resorption immediately and after tooth extraction. Methods The study was conducted on 24 extraction sockets of impacted mandibular third molars bilaterally, vertically, and completely covered, with a thin bony layer. HA/β-TCP was inserted into 12 of the dental sockets immediately after extraction, and the synthetic polymer PLGA was inserted into 12 of the dental sockets. All sockets were covered completely with a full-thickness envelope flap. Follow-up was performed for one year after extraction, using radiographs and stents for the vertical alveolar ridge measurements. Results The mean resorption rate in the HA/β-TCP and PLGA groups was ± 1.23 mm and ± 0.1 mm, respectively. A minimal alveolar bone height reduction of HA/β-TCP was observed after 9 months, the reduction showed a slight decrease to 0.93 mm, while this rate was 0.04 mm after 9 months in the PLGA group. Moreover, the bone height was maintained after three months, indicating a good HA/β-TCP graft performance in preserving alveolar bone (1.04 mm) while this rate was (0.04 mm) for PLGA. Conclusion The PLGA graft demonstrated adequate safety and efficacy in dental socket preservation following tooth extraction. However, HA/β-TCP causes greater resorption at augmented sites than PLGA, which clinicians should consider during treatment planning.

Background Bacterial vaginosis (BV) is a prevalent vaginal condition among reproductive-age women, characterized by off-white, thin vaginal discharge with a fishy odor. It increases susceptibility to sexually transmitted diseases (STDs) and pelvic inflammatory disease (PID). BV involves a shift in vaginal microbiota, with reduced lactobacilli and increased anaerobic bacteria. Standard treatment with oral metronidazole has been shown to have a limited long-term efficacy, possibly due to biofilm persistence. Alternative treatments, such as lactic acid vaginal gel, aim to restore vaginal pH and lactobacilli. This pilot study compares the efficacy and tolerability of lactic acid gel to standard oral metronidazole for acute BV treatment in non-pregnant women. Methods A total of 32 women with acute BV were recruited and assigned to either the treatment group ( n  = 16) where they applied a lactic acid vaginal gel for 12 days, or the control group ( n  = 16) which received 500 mg oral metronidazole twice daily for seven days. A number of objective and subjective parameters including the Amsel score, the Nugent score and a subjective symptom score were recorded at day 0, three weeks, three months, and six months after the study start. Results In the short-term, lactic acid vaginal gel showed inferior clinical (Amsel criteria) and microbiological (Nugent score) cure rates compared to metronidazole. However, it performed equally well regarding subjective symptom improvement and BV recurrence prevention after up to six months. Conclusion Lactic acid vaginal gel was generally very well tolerated and showed mixed but promising results as a stand-alone treatment for acute BV. Trial registration number NCT02042287 (22.01.2014).

Objectives Chemical peels are used to treat photoageing, pigmentation, improve complexion and dull skin, fine lines and scars. The objective of this study is to do comparative analysis of Lactic Acid 30% with Ferulic peel 12% (combination peel) versus TCA 10% with Ferulic peel 12% (combination peel) for Photoageing Skin. Materials and Methods This is a retrospective study from September 2021 to 2022 with total 50 female patients aged between 25 and 40 years were treated. Randomisation of patients was done (simple randomisation using lottery method) for both groups with 25 patients enrolled in each group. The first group (Group A-25 patients) were treated with lactic acid 30% with Ferulic peel 12% (combination peel). The second group (Group B-25 patients) were treated with TCA 10% with Ferulic peel 12% (combination peel). Inclusion and exclusion criteria have been defined for the study. Two scales have been used for assessing the results: Allergan Skin Roughness Scale (ASRS) and Allergan Fine Line Scale (AFLS). ASRS and AFLS scores were assessed at pre-treatment (pre) and post treatment (post-1 month after last peel session). Data were summarised in Mean ± SD (standard deviation). Pre and post groups were compared by paired t test. The pre to post change in outcome measures between two independent groups were compared by independent Student’s t test. Discrete (categorical) groups were compared by Chi-square ( χ 2 ) test. A two-tailed ( α =2) P < 0.05 was considered statistically significant. Analyses were performed on SPSS software (Windows version 22.0). Patients were followed up for 6 months post treatment. Results In Group A, comparing the pre and post ASRS score, paired t test showed significant ( P < 0.001) decrease or improvement of 56.1%. In Group B, comparing the pre and post ASRS score, paired t test showed significant ( P < 0.001) decrease or improvement of 52.8%. Comparing the pre to post mean decrease or improvement in ASRS score of two groups, Student’s t test showed similar ( P > 0.05) improvement between the two groups though it was 2.5% higher in Group B as compared to Group A. In Group A, comparing the pre and post AFLS score, paired t test showed significant ( P < 0.001) decrease or improvement of 63.2% at post as compared to pre. In Group B, comparing the pre and post AFLS score, paired t test showed significant ( P < 0.001) decrease or improvement of 58.8% at post as compared to pre. Further, comparing the pre to post mean decrease or improvement in AFLS score of two groups, Student’s t test showed similar ( P > 0.05) improvement between the two groups though it was 16.7% higher in Group A as compared to Group B. Conclusion Study found both the treatments equally effective in the management of ageing skin after 6 months of treatment. However, study needs further validation on larger sample size, varied age groups and male gender. Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Background We report here two new peritoneal dialysis fluids (PDFs) for Japan [BLR 250, BLR 350 (Baxter Limited, Japan)]. The PDFs use two-chamber systems, and have bicarbonate and lactate buffer to a total of 35 mmol/L. In separate trials, the new PDFs were compared to two “standard” systems [PD-4, PD-2 (Baxter Limited, Japan)]. The trials aimed to demonstrate non-inferiority of peritoneal creatinine clearance (pCcr), peritoneal urea clearance (pCurea) and ultrafiltration volume (UF), and compare acid–base and electrolyte balance. Methods We performed randomized, multicenter, parallel group, controlled, open-label clinical trials in stable continuous ambulatory peritoneal dialysis (CAPD) patients. The primary endpoints were pCcr and UF. The secondary endpoints were serum bicarbonate and peritoneal urea clearance. The active phase was 8 weeks. These trials were performed as non-inferiority studies, with the lower limit of non-inferiority for pCcr and UF set at 3.2 L/week/1.73 m 2 and 0.12 L/day, respectively. Results 108 patients (28 centers) and 103 patients (29 centers) took part in the two trials. Groups were well balanced at baseline. The investigative PDFs were non-inferior to the “standard” ones in terms of primary endpoints, comparable in terms of pCurea, and superior in terms acid–base balance, especially correcting those with over-alkalinization at baseline. Conclusions We demonstrated fundamental functionality of two new PDFs and showed superior acid–base balance. Given the propensity of Japanese CAPD patients for alkalosis, it is important to avoid metabolic alkalosis which is associated with increased cardiovascular mortality risk and accelerated vascular calcification. The new PDFs are important progress of CAPD treatment for Japanese patients.

Background The time course of blood lactate levels could be helpful to assess a patient’s response to therapy. Although the focus of published studies has been largely on septic patients, many other studies have reported serial blood lactate levels in different groups of acutely ill patients. Methods We performed a systematic search of PubMed, Science Direct, and Embase until the end of February 2016 plus reference lists of relevant publications. We selected all observational and interventional studies that evaluated the capacity of serial blood lactate concentrations to predict outcome. There was no restriction based on language. We excluded studies in pediatric populations, experimental studies, and studies that did not report changes in lactate values or all-cause mortality rates. We separated studies according to the type of patients included. We collected data on the number of patients, timing of lactate measurements, minimum lactate level needed for inclusion if present, and suggested time interval for predictive use. Results A total of 96 studies met our criteria: 14 in general ICU populations, five in general surgical ICU populations, five in patients post cardiac surgery, 14 in trauma patients, 39 in patients with sepsis, four in patients with cardiogenic shock, eight in patients after cardiac arrest, three in patients with respiratory failure, and four in other conditions. A decrease in lactate levels over time was consistently associated with lower mortality rates in all subgroups of patients. Most studies reported changes over 6, 12 or 24 hrs, fewer used shorter time intervals. Lactate kinetics did not appear very different in patients with sepsis and other types of patients. A few studies suggested that therapy could be guided by these measurements. Conclusions The observation of a better outcome associated with decreasing blood lactate concentrations was consistent throughout the clinical studies, and was not limited to septic patients. In all groups, the changes are relatively slow, so that lactate measurements every 1–2 hrs are probably sufficient in most acute conditions. The value of lactate kinetics appears to be valid regardless of the initial value.

Pharmaceuticals have been developed for the treatment of a wide range of bone diseases and disorders, but suffer from problematic delivery to the bone marrow. Neutrophils are naturally trafficked to the bone marrow and can cross the bone marrow–blood barrier. Here we report the use of neutrophils for the targeted delivery of free drugs and drug nanoparticles to the bone marrow. We demonstrate how drug-loaded poly(lactic-co-glycolic acid) nanoparticles are taken up by neutrophils and are then transported across the bone marrow–blood barrier to boost drug concentrations in the bone marrow. We demonstrate application of this principle to two models. In a bone metastasis cancer model, neutrophil delivery is shown to deliver cabazitaxel and significantly inhibit tumour growth. In an induced osteoporosis model, neutrophil delivery of teriparatide is shown to significantly increase bone mineral density and alleviate osteoporosis indicators. Systemic drug delivery to the bone marrow is limited, currently requiring high doses of drug, increasing the risk of side effects. Here, the authors report on the hitchhiking of drug nanoparticles in neutrophils using their natural homing to the bone marrow for targeted delivery, and demonstrate its application.

Lactic acidosis has been reported in solid tumor microenvironment (TME) including glioblastoma (GBM). In TME, several signaling molecules, growth factors and metabolites have been identified to induce resistance to chemotherapy and to sustain immune escape. In the early phases of the disease, microglia infiltrates TME, contributing to tumorigenesis rather than counteracting its growth. Insulin-like Growth Factor Binding Protein 6 (IGFBP6) is expressed during tumor development, and it is involved in migration, immune-escape and inflammation, thus providing an attractive target for GBM therapy. Here, we aimed at investigating the crosstalk between lactate metabolism and IGFBP6 in TME and GBM progression. Our results show that microglia exposed to lactate or IGFBP6 significantly increased the Monocarboxylate transporter 1 (MCT1) expression together with genes involved in mitochondrial metabolism. We, also, observed an increase in the M2 markers and a reduction of inducible nitric oxide synthase (iNOS) levels, suggesting a role of lactate/IGFBP6 metabolism in immune-escape activation. GBM cells exposed to lactate also showed increased levels of IGFBP6 and vice-versa. Such a phenomenon was coupled with a IGFBP6-mediated sonic hedgehog (SHH) ignaling increase. We, finally, tested our hypothesis in a GBM zebrafish animal model, where we observed an increase in microglia cells and igfbp6 gene expression after lactate exposure. Our results were confirmed by the analysis of human transcriptomes datasets and immunohistochemical assay from human GBM biopsies, suggesting the existence of a lactate/IGFBP6 crosstalk in microglial cells, so that IGFBP6 expression is regulated by lactate production in GBM cells and in turn modulates microglia polarization.

Background Many HIV patients receiving antiretroviral treatment develop lipodystrophy. NEW-FILL ® is a polylactic acid injected to treat facial lipoatrophy. The objectives of this study were to describe (1) change in quality of life (QoL) of HIV patients treated with NEW-FILL ® in the management of facial lipoatrophy; (2) efficacy of NEW-FILL ® using facial photographs and (3) a patient-reported “Overall Treatment Effect” (OTE) scale; and (4) safety of NEW-FILL ® . Methods Doctors from 13 treatment centres recruited 230 HIV patients to receive up to 5 sessions of NEW-FILL ® injections. Patients self-reported QoL with the ABCD questionnaire before the first set of injections, at 2 months and at 12 to 18 months after the last session of injections. Efficacy was evaluated at each interval through photographs and OTE scale. Safety was evaluated via Case Report Form (CRF) data. Results 64.4% of patients reported QoL improvements of >10% at 2 months, and 58.8% at 12–18 months. Lipoatrophy grades improved at each visit (“no lipoatrophy” or “limited lipoatrophy”: 20.3% at inclusion, 77.4% at 2 months, 58.4% at 12–18 months). Average OTE scores of 5.3 and 5.0 at 2 and 12–18 months indicated “moderate improvement”. Minimum Important Difference (MID) in QoL score was 7.1 points at 2 months; 7.4 points at 12–18 months. For 911 injection sessions performed, 3.4% resulted in “immediate” adverse events, 7% in “non-immediate” events, and 1.7% in “other” events. Conclusions Improvements to quality of life and diminished lipoatrophy visibility were observed in the months immediately following NEW-FILL ® treatment and were maintained 12–18 months post-treatment. Most adverse events were mild and transient. ABCD MID thresholds provide clinicians with means to assess the impact of lipoatrophy therapies on QoL.